REVIEW | doi:10.20944/preprints201612.0099.v1
Subject: Medicine & Pharmacology, Pharmacology & Toxicology Keywords: aging; bioactive nutrients; dietary; nutrigenomics; Oxiinflammaging
Online: 19 December 2016 (09:37:23 CET)
The increase in the average lifespan and the consequent proportional growth of the elderly segment of society has furthered the interest in studying ageing processes. Ageing may be considered a multifactorial process derived from the interaction between genetic and environmental factors including lifestyle. There is ample evidence in many species that the maximum age attainable (maximum lifespan potential, MLSP) is genetically determined and several mitochondrial DNA polymorphisms are associated with longevity. Many studies have shown that most of the phenotypic characteristics observed in the aging process are the result of the occurrence, with age, of a low grade chronic pro-inflammatory status called "inflammaging", partially under genetic control. The term indicate that aging is accompanied by a low degree of chronic inflammatory, an up-regulation of inflammatory response and that inflammatory changes are common to many age-related diseases. Therefore, the theory of oxidation-inflammation was proposed as the main cause of aging. Accordingly, the chronic oxidative stress, that appears with age, affects all cells and especially those of the regulatory systems, such as the nervous, endocrine, and immune systems and the communication between them. This prevents an adequate homeostasis and, therefore, the preservation of health. It was also proposed that the immune system plays a key role in the aging process, specifically in the rate of aging, since there is a relationship between the redox state and functional capacity of immune cells and longevity of individuals. Moreover, the role of the immune system in senescence could be of universal application. A confirmation of the central role of the immune system in oxi-inflamm-aging is that the administrationintake? of adequate amounts of antioxidants in the diet improves immune function, decreases their oxidative stress, and consequently increases longevity. The promotion of healthy lifestyles is one of the major goals of governments and international agencies all over the world. Human molecular processes are influenced by both physiological pathways and exogenous factors which include, for instance, those originating from diet. Dietary intake has substantive effects on molecular processes of metabolic health. Nutrients can directly regulate physiological changes in human body. In fact, in addition to have an energetic and structural value, nutritional intake provides bioactive molecules which are selectively able to modulate specific metabolic pathways, noticeably affecting cardiovascular and neoplastic diseases development or progress. Numerous bioactive nutrients are being progressively identified and their chemopreventive effects are being described at clinical and molecular mechanism levels. Systematic analyses comprise all “omics” technologies (such as transcriptomics, proteomics and metabolomics) and the goal is to investigate bioactive molecules effects derived from the diet. Nutrigenomic knowledge on physiologic status and disease risk will provide both developments of better diagnostic procedures and of new therapeutic strategies specifically targeted on nutritionally relevant processes. The present review was aimed to understand the molecular mechanisms underlying beneficial effects of bioactive nutrients and nutrigenomics on age-related diseases.
ARTICLE | doi:10.20944/preprints201608.0182.v1
Subject: Engineering, Marine Engineering Keywords: aging offshore jacket platform; safety assessment; analytic hierarchy process; grey clustering method
Online: 20 August 2016 (05:26:34 CEST)
It is a significant task to assess the safety of the aging offshore jacket platform in order to extend the service life. This paper analyzes the multiple risk factors of an aging jacket platform in Bohai Bay, China and builds the safety evaluation index system, which includes three levels, namely, the target layer, the first-grade indicators layer and the second-grade indicators layer. The target layer consists of three first-grade indicators: ocean environments, structure status, and human and organizational factors. Each first-grade indicator is divided into three second-grade indicators. The weight of each indicator is calculated by analytic hierarchy process to weaken subjective effect. Grey clustering method is applied to estimate the failure risk of the platform in Bohai Bay qualitatively and quantitatively. The assessment standard is divided into five grades and the whitening function of each grey cluster is determined by the assessment scheme. The grey evaluation weight vector of each second-grade indicator is calculated by the table dispatching method. Through layer by layer calculation, the grey assessment value of the target layer is finally estimated by making the grey assessment weight vector single-value and the grey grade is determined according to the maximum principle. The evaluation results show quantitatively that the failure risk grade of the jacket platform in Bohai Bay is medium and the safety assessment method is reasonable and feasible.
ARTICLE | doi:10.20944/preprints201805.0433.v1
Subject: Life Sciences, Other Keywords: primary health care; workforce crisis; general practitioner vacancy; aging of general practitioners; premature mortality
Online: 30 May 2018 (05:47:53 CEST)
The workforce crisis of primary care is reflected in the increasing number of general medical practices (GMP) with vacant general practitioner (GP) position, and the GPs’ ageing. Our study aimed to describe the association between this crisis and premature mortality. Age-sex-standardized mortality for 18-64 years old adults were calculated for all Hungarian GMPs annually in the period from 2006 to 2014. The relationship of premature mortality with GPs’ age and vacant GP position were evaluated by standardized linear regression controlled for list size, urbanization, geographical location, clients’ education, and type of the GMP. The clients’ education was the strongest protective factor (beta=-0175; p<0.001), followed by urban residence (beta=-0.149; p<0.001), and the bigger list size (beta1601-2000=-0.054; p<0.001; beta2001-X=-0.096; p<0.001). The geographical localization influenced significantly also the risk. Although, GMP with a GP aged older than 65 years (beta=0; p=0.995) did not affected the risk, GP vacancy was associated with higher risk (beta=0.010; p=0.033), but the corresponding number of attributable cases was 23.54 for 9 years. The vacant GP position is associated with significant but hardly detectable increased risk of premature mortality without considerable public health importance. Nevertheless, employment of GPs aged more than 65 does not impose premature mortality risk elevation.
REVIEW | doi:10.20944/preprints202004.0182.v2
Subject: Biology, Other Keywords: COVID-19; pandemic; comorbidity; aging; hallmarks of aging; anti-aging
Online: 16 May 2020 (18:25:28 CEST)
Within the past several decades, the emergence of new viral diseases with severe health complications and mortality is evidence of an age-dependent, compromised bodily response to abrupt stress with concomitantly reduced immunity. The new severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, causes coronavirus disease 2019 (COVID-19). It has increased morbidity and mortality in persons with underlying chronic diseases and those with a compromised immune system regardless of age and in older adults who are more likely to have these conditions. While SARS-CoV-2 is highly virulent, there is variability in the severity of the disease and its complications in humans. Severe pneumonia, acute respiratory distress syndrome, lung fibrosis, cardiovascular events, acute kidney injury, stroke, hospitalization, and mortality have been reported that result from pathogen–host interactions. Hallmarks of aging, interacting with one another, have been proposed to influence health span in older adults, possibly via mechanisms regulating the immune system. Here, we review the potential roles of the hallmarks of aging coupled with host–coronavirus interactions. Of these hallmarks, we focused on those that directly or indirectly interact with viral infections, including immunosenescence, inflammation and inflammasomes, adaptive immunosenescence, genomic instability, mitochondrial dysfunction, telomere attrition, epigenetic alterations, and impaired autophagy. These hallmarks likely contribute to the increased pathophysiological responses to SARS-CoV-2 among older adults and may play roles as an additive risk of accelerated biological aging even after recovery. We also briefly discuss the role of anti-aging drug candidates that require paramount attention in COVID-19 research.
REVIEW | doi:10.20944/preprints201807.0601.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: aging; disability; healthy aging; osteoarthritis; pain, rehabilitation, successful aging
Online: 30 July 2018 (22:20:03 CEST)
Background: Aging is commonly accepted as a time period of declining heath. Aims: This review aimed to examine the research base concerning the use of term ‘successful aging’, a process and outcome deemed desirable, but challenging to attain. A second was to provide related information to demonstrate how health professionals as well as individuals can aim for a ‘successful aging’ process and outcome, despite the presence of disabling osteoarthritis. Methods: Information specifically focusing on ‘successful aging’ and the concept of improving opportunities for advancing ‘successful aging’ despite osteoarthritis was sought. Results: Among the many articles on ‘successful aging’, several authors highlight the need to include, a broader array of older adults into the conceptual framework. Moreover, conditions such as osteoarthritis should not necessarily preclude the individual from attaining a personally valued successful aging outcome. Conclusion: Pursuing more inclusive research and research designs, and not neglecting to include people with chronic osteoarthritis can potentially heighten the life quality of all aging individuals, while reducing pain and depression, among other adverse aging and disability correlates among those with osteoarthritis
ARTICLE | doi:10.20944/preprints202210.0018.v1
Subject: Behavioral Sciences, Developmental Psychology Keywords: Antisocial Trajectories; Biological Aging; Crime; Accelerated aging
Online: 4 October 2022 (10:47:36 CEST)
Prior research shows that individuals who have exhibited antisocial behavior are in poorer health than their same-aged peers. A major driver of poor health is aging itself, yet research has not investigated relationships between offending trajectories and biological aging. We tested the hypothesis that individuals following a life-course persistent (LCP) antisocial trajectory show accelerated aging in midlife. Trajectories of antisocial behavior from age 7 to 26 years were studied in the Dunedin Multidisciplinary Health and Development Study, a population-representative birth cohort (N=1037). Signs of aging were assessed at age 45 years using previously validated measures including biomarkers, clinical tests, and self-reports. First, we tested whether the association between antisocial behavior trajectories and midlife signs of faster aging represented a decline from initial childhood health. We then tested whether decline was attributable to tobacco smoking, antipsychotic medication use, debilitating illnesses in adulthood, adverse exposures in childhood (maltreatment, socioeconomic disadvantage) and adulthood (incarceration), and to childhood self-control difficulties. Study members with a history of antisocial behavior had a significantly faster pace of biological aging by midlife, and this was most evident among individuals following the LCP trajectory (β, .22, 95%CI, .14, .28, p.001). This amounted to 4.3 extra years of biological aging between ages 25-45 years for Study members following the LCP trajectory compared to low-antisocial trajectory individuals. LCP offenders also experienced more midlife difficulties with hearing (β, -.14, 95%CI, -.21, -.08, p.001), balance (β, -.13, 95%CI, -.18, -.06, p.001), gait speed (β, -.18, 95%CI, -.24, -.10, p.001), and cognitive functioning (β, -.25, 95%CI, -.31, -.18, p.001). Associations represented a decline from childhood health. Associations persisted after controlling individually for tobacco smoking, antipsychotic medication use, midlife illnesses, maltreatment, socioeconomic status, incarceration, and childhood self-control difficulties. However, the cumulative effect of these lifestyle characteristics together explained why LCP offenders have a faster Pace of Aging than their peers. While older adults typically age-out of crime, LCP offenders will likely age-into the healthcare system earlier than their chronologically same-aged peers. Preventing young people from offending is likely to have substantial benefits for health, and people engaging in a LCP trajectory of antisocial behaviors might be the most in need of health promotion programs. We offer prevention and intervention strategies to reduce the financial burden of offenders on health care systems and improve their wellbeing.
ARTICLE | doi:10.20944/preprints201810.0733.v1
Subject: Life Sciences, Molecular Biology Keywords: prefrontal cortex aging; meta-analysis of transcriptomic; synapsis aging; reactive astrogliosis
Online: 31 October 2018 (05:02:17 CET)
Prefrontal cortex (PFC) is one of the brain regions with more prominent changes in human aging. The molecular processes related to the aging cognitive decline and mood changes are not completely understood. In order to improve our knowledge, we integrated transcriptomic data of four studies of human PFC from old people -58-80 years old- compared with young people -20-40 years old- using a meta-analytic approximation combined with molecular signature analysis. We identified 1816 differentially expressed genes -561 up-regulated and 1256 down-regulated. Pathway analysis revealed down-regulation of synaptic genes with conservation of gene expression of other neuronal regions. Additionally, we identified up-regulation of markers of astrogliosis with transcriptomic signature compatible with A1 neurotoxic astrocytes and A2 neuroprotective astrocytes. Response to interferon is related to A1 astrocytes and the A2 phenotype is mediated in aging by activation of SHH pathway and up-regulation of metallothioneins I and genes of the family EZR -ezrin, radixin, and moesin-. The main conclusions of our study are the confirmation that in aged PFC there is a global dysfunction of the synapses and we reported for the first time opposite phenotypes of astrogliosis because of brain aging.
CONCEPT PAPER | doi:10.20944/preprints202205.0212.v1
Subject: Biology, Physiology Keywords: aging; antagonistic pleiotropy; biological constraint; hyperfunction; hypofunction; programmatic aging; trade-off
Online: 16 May 2022 (14:02:16 CEST)
Aging rate differs greatly between species, indicating that the process of senescence is largely genetically determined. Senescence evolves in part due to antagonistic pleiotropy (AP), where selection favors gene variants that increase fitness earlier in life but promote pathology later. Identifying the biological mechanisms by which AP causes senescence is key to understanding the endogenous causes of aging and its attendant diseases. Here we argue that the frequent occurrence of AP as a property of genes reflects the presence of constraint in the biological systems that they specify. This arises particularly because the functionally interconnected nature of biological systems constrains the simultaneous optimization of coupled traits (interconnection constraints), or because individual traits cannot evolve (impossibility constraints). We present an account of aging that integrates AP and biological constraint with recent programmatic aging concepts, including costly programs, quasi-programs, hyperfunction and hypofunction. We argue that AP mechanisms of costly programs and triggered quasi-programs are consequences of constraint, in which costs resulting from hyperfunction or hypofunction cause senescent pathology. Impossibility constraint can also cause hypofunction independently of AP. We also describe how AP corresponds to Stephen Jay Gould’s constraint-based concept of evolutionary spandrels, and argue that pathologies arising from AP are bad spandrels. Biological constraint is a missing link between ultimate and proximate causes of senescence, including diseases of aging. That this was not realized previously may reflect a combination of hyperadaptationism among evolutionary biologists, and the erroneous assumption by biogerontologists that molecular damage accumulation is the principal primary cause of aging.
Subject: Medicine & Pharmacology, General Medical Research Keywords: aging; microRNA; sarcopenia; cytokine
Online: 20 August 2020 (07:39:53 CEST)
Age-related sarcopenia meaningfully increases the risks of functional limitations and mortality in the elderly. Although circulating microRNAs (c-miRNAs) are associated with aging-related cellular senescence and inflammation, the relationships between c-miRNAs and sarcopenia in the elderly remain unclear. This study investigates whether circulating myo-miRNAs and inflammation-related miRNAs are associated with sarcopenia in the elderly. This study recruited 77 eligible subjects (41 males and 36 females) from 597 community-dwelling older adults, and then divided into normal (n=24), dynapenic (loss of muscular function without mass, n=35), and sarcopenic groups (loss of muscular function with mass, n=18). Moreover, myo-miRNAs (c-miRNA-133a and c-miRNA-486), inflammation-related miRNAs (c-miRNA-21 and c-miRNA-146a), and inflammatory-related cytokine levels in plasma were determined using quantitative polymerase chain reaction and ELISA, respectively. The results demonstrated that sarcopenic group exhibited lesser skeletal muscle mass index (SMI), handgrip strength, and gait speed, as well as, lower c-miR-486 and c-miR-146a levels, compared to those of normal and dynapenic groups. Moreover, c-miR-486 level was positively related to SMI (r=0.334, P=0.003), whereas c-miR-146a level was positively associated with SMI (r=0.240, P=0.035) and handgrip strength (r=0.253, P=0.027). In the receiver operating characteristic analysis for predicting sarcopenia, the area under the curve in c-miR-486 was 0.708 (95% confidence interval: 0.561-0.855, P=0.008) and c-miR-146a was 0.676 (95% CI: 0.551-0.801, P=0.024). However, no significant relationships were observed between SMI/ handgrip strength/gait speed and plasma myeloperoxidase/interleukin-1?/interleukin-6 levels. In conclusion, myo-miRNA (c-miR-486) and inflammation-related miRNA (c-miR-146a) are superior to inflammatory peroxide/cytokines in plasma for serving as critical biomarkers of age-related sarcopenia.
ARTICLE | doi:10.20944/preprints201809.0490.v1
Online: 25 September 2018 (15:43:11 CEST)
Background: Melatonin is a potent mitochondrial, cytoprotective and antioxidant molecule with potentially strong anti-aging properties. Topical melatonin has shown to improve the clinical signs of skin aging. Melatosphere™ is a new lipid-based delivery system able to improve stability and skin penetration of melatonin when used in topical formulations. No clinical studies, using objective instrumental data, are available so far regarding the positive effect of Melatosphere™ in improving wrinkles in women with mild-to-moderate skin aging. Study Aim: We evaluate, in an open prospective, evaluator-blinded trial, the effects on skin texture of 2 months treatment with a Melatosphere™ based cream. Subjects and Methods: 15 women aged >45 years with mild to moderate facial skin aging (Glogau score ≥2) participated in the trial, after their informed consent. An ANTERA 3D computer-assisted skin analysis evaluation for the assessment of coarse and fine wrinkles of the periorbital area and melanin content was performed at baseline and after two months of treatment. An evaluator-blinded Investigator Global assessment of skin elastosis, roughness, level of dyscromia, skin dryness and presence of actinic damage was also performed at the same time points using a 4-grade score from 0 (no sign) to 3 (severe sign). Results: At baseline the mean (SD) IGA score was 8.2(1.0). After 2 months the IGA score significantly decrease to 4.2(1.4) (49% reduction) (P=0.0007). ANTERA 3D evaluations showed a significant reduction in skin coarse and fine wrinkles volume in the target area of -31% and -18%, respectively. Melanin content was reduced significantly by -17%. Conclusion: Topical melatonin carried in Melatosphere improves in the short-term signs of skin aging evaluated clinically and by ANTERA 3D device in women with mild to moderate skin aging.
ARTICLE | doi:10.20944/preprints202212.0250.v1
Online: 14 December 2022 (06:51:24 CET)
The transcriptional coactivators YAP (Yes-associated protein) and TAZ (transcriptional coactivator with PDZ-binding motif) are the main downstream effectors of the evolutionary conserved Hippo signaling pathway. YAP/TAZ is implicated in the transcriptional regulation of target genes that are involved in a wide range of key biological processes affecting tissue homeostasis and play dual roles in the aging process depending on cellular and tissue context. The aim of the present study was to investigate whether pharmacological inhibitors of Yap/Taz may increase the lifespan of Drosophila melanogaster. qRT-PCR was performed to measure the changes in the expression level of Yki (Yorkie, the Drosophila homolog of YAP/TAZ) target genes. We have revealed a lifespan increasing effect of YAP/TAZ inhibitors that was mostly associated with decreased expression level of wg and E2f1 genes. However further analysis is required to understand how YAP/TAZ pathway is linked with aging.
SHORT NOTE | doi:10.20944/preprints202005.0035.v1
Subject: Life Sciences, Immunology Keywords: COVID-19; Chronic diseases; Aging; Immune response; Public health; Healthy Aging
Online: 3 May 2020 (08:15:24 CEST)
As the novel COVID-19 disease spreads around the world, the most affected population are those who suffer from the most common chronic diseases, such as obesity, hypertension, and type 2 diabetes, which are quite associated with the so-called age-related diseases. On the other hand, since the Spanish influenza outbreak, humanity has not experienced an infectious disease that synergizes so quickly with chronic diseases, making it mortal for those individuals with comorbidities. In this context, COVID-19 is challenging for health systems all around the world due to the high prevalence of chronic diseases. Nowadays, we are facing the beginning of a new era in which health infectious and chronic diseases meet. Therefore, epidemiologic and biomedical researchers must work together to solve further contingencies, and politicians should direct science-centered decisions on public health. In the present paper, we make an urgent call to learn from the COVID-19 lessons in order to mitigate the chronic diseases prevalence and to address the influence of the infectious diseases on the aging process; since we are about to begin the Decade of Healthy Aging.
REVIEW | doi:10.20944/preprints202105.0409.v1
Subject: Life Sciences, Biochemistry Keywords: Macrophages; Senescence; Immunosenescence; Immunometabolism; Aging
Online: 18 May 2021 (10:15:20 CEST)
An intricate relationship between impaired immune functions and the age-related accumulation of tissue senescent cells (SC) is rapidly emerging. The immune system is unique as it undergoes mutually inclusive and deleterious processes of immunosenescence and cellular senescence with advancing age. While factors inducing immunosenescence and cellular senescence may be shared, however, both these processes are fundamentally different which holistically influence the aging immune system. Immunosenescence is a well-characterized phenomenon, but our understanding and biological impact of cellular senescence in immune cells, especially in the innate immune cells such as macrophages, is only beginning to be understood. Tissue-resident macrophages are long-lived, and while functioning in tissue-specific and niche-specific microenvironments, senescence in macrophages can be directly influenced by senescent host cells which may impact organismal aging. In addition, evidence of age-associated immunometabolic changes as drivers of altered macrophage phenotype and functions such as inflamm-aging is also emerging. The present review describes the emerging impact of cellular senescence vis-à-vis immunosenescence in aging macrophages, its biological relevance with other senescent non-immune cells, and known immunometabolic regulators. Gaps in our present knowledge, as well as strategies aimed at understanding cellular senescence and its therapeutics in the context of macrophages, have been reviewed.
ARTICLE | doi:10.20944/preprints202101.0432.v1
Online: 22 January 2021 (08:40:26 CET)
We have previously demonstrated that the acute ingestion of essential amino acids may augment net protein balance in the elderly. Using a double blind, randomized controlled trial, our objective was to compare an experimental meal replacement enriched with essential amino acids (EMR) compared to a commercial meal replacement (Optifast®) provided once/day (q.d.) for four weeks on body composition and physical function in older, obese participants. Twenty-seven individuals (69±5 yrs; body mass index of 32±4 kg/m2) were randomly assigned to EMR (n=13) or Optifast® (n=15) supplementation. Measurements of body composition, skeletal muscle cross-sectional area (CSA), intrahepatic lipid and physical function were completed pre- and post-supplementation. Body mass, fat mass, and visceral fat mass were reduced with EMR but not altered with Optifast®. Thigh muscle CSA increased ( 4.1 ± 1.9 cm2, P = 0.03) with EMR but not Optifast®. There was a significant increase in the distance covered during the six-minute walk test with EMR ( 21±26 m) but no change in Optifast® ( 22±54 m). Improvements in body composition and physical function support the efficacious use of EMR-based meal replacements in the obese elderly.
REVIEW | doi:10.20944/preprints202105.0310.v1
Subject: Medicine & Pharmacology, Allergology Keywords: aging; geroscience; hallmarks; paradigm; senescence; theory
Online: 13 May 2021 (14:29:48 CEST)
With the goal of representing common denominators of aging in different organisms López-Otín et al. in 2013 described nine hallmarks of aging. Since then, this representation has become a major reference point for the biogerontology field. The template for the hallmarks of aging account originated from landmark papers by Hanahan and Weinberg (2000, 2011) defining first six and later ten hallmarks of cancer. Here we assess the strengths and weaknesses of the hallmarks of aging account. As a checklist of diverse major foci of current aging research, it has provided a useful shared overview for biogerontology during a time of transition in the field. It also seems useful in applied biogerontology, to identify interventions (e.g. drugs) that impact multiple symptomatic features of aging. However, while the hallmarks of cancer provide a paradigmatic account of the causes of cancer with profound explanatory power, the hallmarks of aging do not. A worry is that as a non-paradigm the hallmarks of aging have obscured the urgent need to define a genuine paradigm, one that can provide a useful basis for understanding the mechanistic causes of the diverse aging pathologies. We argue that biogerontology must look and move beyond the hallmarks to understand the process of aging.
REVIEW | doi:10.20944/preprints202108.0552.v1
Subject: Life Sciences, Cell & Developmental Biology Keywords: antagonistic pleiotropy; insulin/IGF-1 signalling; hyperfunction; quasi-programs; mTOR; theories of aging; programmatic aging
Online: 30 August 2021 (16:11:02 CEST)
The process of senescence (aging) is largely determined by the action of wild-type genes. For most organisms, this does not reflect any adaptive function of senescence, but rather evolutionary effects of declining selection against genes with deleterious effects later in life. To understand aging requires an account of how evolutionary mechanisms give rise to pathogenic gene action and late-life disease, that integrates evolutionary (ultimate) and mechanistic (proximate) causes into a single explanation. A well-supported evolutionary explanation by G.C. Williams argues that senescence can evolve due to pleiotropic effects of alleles with antagonistic effects on fitness and late-life health (antagonistic pleiotropy, AP). What has remained unclear is how gene action gives rise to late-life disease pathophysiology. One ultimate-proximate account is T.B.L. Kirkwood’s disposable soma theory. Based on the hypothesis that stochastic molecular damage causes senescence, this reasons that aging is coupled to reproductive fitness due to preferential investment of resources into reproduction, rather than somatic maintenance. An alternative and more recent ultimate-proximate theory argues that aging is largely caused by programmatic, developmental-type mechanisms. Here ideas about AP and programmatic aging are reviewed, particularly those of M.V. Blagosklonny (the hyperfunction theory) and J.P. de Magalhães (the developmental theory), and their capacity to make sense of diverse experimental findings is described.
REVIEW | doi:10.20944/preprints202109.0182.v1
Online: 10 September 2021 (11:07:13 CEST)
The biology of aging is focused on the identification of novel pathways that regulate the underlying processes of aging to develop interventions aimed at delaying the onset and progression of chronic diseases to extend lifespan. However, the research on the aging field has been conducted mainly in animal models, yeast, Caenorhabditis elegans and cell culture. Thus, it is unclear to what extent this knowledge is transferable to humans since they might not reflect the complexity of aging in people. Organoid culture is an in vitro 3D cell-culture technology that reproduces the physiological and cellular composition of the tissues and/or organs. This technology is being used in the cancer field to predict the response of a patient-derived tumor to a certain drug or treatment serving as patient stratification and drug-guidance approaches. Modeling aging with patient-derived organoids has a tremendous potential as a preclinical model tool to discover new biomarkers of aging, to predict adverse outcomes during aging and to design personalized approaches for prevention and treatment of aging-related diseases and geriatric syndromes. This could represent a novel approach to study chronological and/or biological aging paving the way to personalized interventions targeting the biology of aging.
ARTICLE | doi:10.20944/preprints202110.0004.v2
Subject: Engineering, Energy & Fuel Technology Keywords: cycle aging; Lithium battery; stochastic algorithm
Online: 29 October 2021 (12:08:24 CEST)
The prediction of capacity degradation, and more generally of the behaviors related to battery aging, is useful in the design and use phases of a battery to help improve the efficiency and reliability of energy systems. In this paper, a stochastic model for the prediction of battery cell degradation is presented. The proposed model takes its cue from an approach based on Markov chains, although it is not comparable to a Markov process, as the transition probabilities vary as the number of cycles that the cell has performed varies. The proposed model can reproduce the abrupt decrease in the capacity that occurs near the end of life condition (80% of the nominal value of the capacity) for the cells analyzed. Furthermore, we illustrate the ability of this model to predict the capacity trend for a lithium-ion cell with nickel-manganese-cobalt (NMC) at the cathode and graphite at the anode subjected to a life cycle in which there are different aging factors, using the results obtained for cells subjected to single aging factors.
REVIEW | doi:10.20944/preprints201805.0014.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: osteosarcopenic obesity; exercise; diet; aging; fall
Online: 2 May 2018 (08:02:13 CEST)
Osteosarcopenic obesity (OSO) is described by the simultaneous presence of osteopenia/osteoporosis, sarcopenia, and increased adiposity. Over time, older adults with OSO syndrome might be at greater risk for loss of physical function and bone fractures. Furthermore, a sedentary lifestyle, inadequate nutrition, pharmaceutical drugs and chronic conditions encompass the multifactorial nature of OSO syndrome. Physical activity and a healthy diet play a crucial role in management and treatment of OSO syndrome. Research has shown that even low-intensity physical activity or daily habitual activity can maintain bone mineral density, muscle strength and improve muscle quality, and reduce adiposity. However, older adults with high risk of fall and injuries require tailored exercise intensity. Also, balanced daily intake of vitamin D, calcium and protein is important in prevention and treatment of OSO syndrome in postmenopausal women. Effective measurement of bone mass, muscle mass and strength is required when detecting OSO syndrome and to evaluate the balance, strength and endurance of elder individuals and severity of the condition.
REVIEW | doi:10.20944/preprints202011.0728.v1
Subject: Biology, Anatomy & Morphology Keywords: mitochondrial permeability transition; aging; longevity; aging-driven degenerative disease; Reactive Oxygen Species; mitophagy; autophagy; Parkinson’s disease
Online: 30 November 2020 (12:53:43 CET)
The activity of the mitochondrial Permeability Transition Pore, mPTP, a highly regulated multi-component mega-channel, is enhanced in aging and in aging-driven degenerative diseases. mPTP activity accelerates aging by releasing large amounts of cell-damaging Reactive Oxygen Species, Ca2+ and NAD+. The various pathways that control the channel activity, directly or indirectly, can therefore either, inhibit, or accelerate aging, retards, or enhance the progression of aging-driven degenerative diseases, and determine lifespan and healthspan. Autophagy, a catabolic process that removes and digests damaged proteins and organelles protects the cell against aging and disease. However, the protective effect of autophagy depends on mTORC2/SKG1 inhibition of mPTP. Autophagy is inhibited in aging cells. Mitophagy, a specialized form of autophagy, which retards aging by removing mitochondrial fragments with activated mPTP, is also inhibited in aging cells, and this inhibition leads to increased mPTP activation, which is a major contributor to neurodegenerative diseases, such as Alzheimer’s and Parkinson’s Diseases. The Increased activity of mPTP in aging turns autophagy/mitophagy into a destructive process leading to cell aging and death. Several drugs and lifestyle modifications that enhance healthspan and lifespan enhance autophagy and inhibit the activation of mPTP. Therefore, elucidating the intricate connections between pathways that activate and inhibit mPTP, in the context of aging and degenerative diseases, could enhance the discovery of new drugs and lifestyle modifications that slow aging and degenerative disease.
ARTICLE | doi:10.20944/preprints202203.0319.v1
Online: 24 March 2022 (02:20:36 CET)
We have developed a self-consistent model for predicting velocity of 1/2 screw dislocation in binary iron--carbon alloys gliding by a high-temperature Peierls mechanism. The methodology of modelling includes: (i) Kinetic Monte-Carlo (kMC) simulation of carbon segregation in dislocation core and determination the total carbon occupancy of the core binding sites; (ii) Determination of kink-pair formation enthalpy of a screw dislocation in iron---carbon alloy; (iii) KMC simulation of carbon drag and determination of maximal dislocation velocity at which the atmosphere of carbon atoms can follow a moving screw dislocation; (iv) Self consistent calculation of average velocity of screw dislocation in binary iron--carbon alloys gliding by a high-temperature kink-pair mechanism under constant strain rate. We conduct a quantitative analysis of the conditions of stress and temperature at which screw dislocation glide in iron--carbon alloy is accomplished by a high-temperature kink-pair mechanism. We estimate the dislocation's velocity at which screw dislocation brakes away from the carbon cloud and thermally-activated smooth dislocation propagation is interrupted by sporadic bursts controlled by athermal dislocation activity.
ARTICLE | doi:10.20944/preprints202008.0485.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: DEXA; BMD; BMC; Osteoporosis; BMI; Aging
Online: 21 August 2020 (11:29:10 CEST)
Dual energy X-ray absorptiometry (DEXA) measuring tool is a reliable and accurate technology to measure bone density and bone mineral composition. This research examined the composition and bone density (bone mineral composition and bone mineral density) of the whole body and representative body parts using DEXA. The participants were 240 healthy adult men and women who were divided into three groups based on age. The total bone mineral density (BMD) of women amounted to an average of 1.14 g/㎠ in Group A, 1.14 g/㎠ in Group B, and 0.98 g/㎠ in Group C. For men, the average BMD was 1.25 g/㎠ in Group A, 1.20 g/㎠ in Group B, and 1.17 g/㎠ in Group C. As a result, the reduction of age-specific BMD was shown to have a correlation with aging and body mass index(BMI), and it is determined that exercising on a regular basis can prevent reduction in BMD by maintaining appropriate muscle mass.
Subject: Medicine & Pharmacology, Allergology Keywords: aging; aerobic exercise; vascular occlusion; electromyography
Online: 19 March 2021 (11:11:26 CET)
Background and Objectives: Blood flow restriction (BFR) has been investigated as an alternative method combined with resistance training or AT to promote different health benefits for older people. Nevertheless, no study analyzed chronic effects of BFR on muscle activation in this population, and in some investigations, the application of BFR has been employed arbitrary pressures, which can be a serious methodological error, both from the results and of the risk to the health of the older. Thus, this study analyzed the effect of 24 weeks of walking with BFR on activation and muscle strength in elderly women with osteoporosis. Materials and Methods: Thirty older women (66.0±4.6 years) performed randomly to one of three training groups: WALK (moderate-intensity walking), WALK+BFR (low-intensity walking with BFR), or BFR (BFR alone). Muscle activation (sEMG) and strength of knee flexors and extensors were measured pre-intervention and after 12 and 24 weeks. Results: Only a trivial effect size (ES) for the WALK+BFR (ES= 0.16) was observed in sEMG of the knee flexors compared to WALK. A moderate effect was observed in sEMG of the knee extensors (ES= 0.65) for the WALK+BFR compared to the WALK. However, adverse effects were found in the strength of the knee flexors for the BFR (ES= −0.86) and WALK+BFR (ES= −0.69) compared to WALK. Adverse and null effects, respectively for the BFR (ES= −0.16) and WALK+BFR (ES= 0.06) groups, were also observed on the strength gain of the knee extensors. Conclusions: Low-intensity walk combined with BFR does not provide relevant chronic effects on strength gain or even limit muscle strength gain, however, due to greater activation of knee extensors over 24 weeks, it is possible to benefit from the use of similar strategies to obtain neuromuscular gains in the long‐term for elderly women with osteopenia and osteoporosis.
Subject: Life Sciences, Biochemistry Keywords: skin aging; punicalagin; niosomes; UV radiation; collagen
Online: 24 March 2021 (17:35:18 CET)
Skin aging is one of the most common problems facing humanity. It occurs because of altering the balance between free radicals and antioxidants and increasing the amount of the reactive oxygen species (ROS) in skin cells, which leads to oxidative stress especially when exposed to UV radiation. Antioxidants can neutralize the harmful effects of ROS, and secondary plant metabolites can help protect against UV radiation. In this study, punicalagin was extracted from pomegranate and concentrations of total polyphenolics and flavonoids were determined and antioxidant activities measured. Punicalagin was loaded onto niosomes and its morphology and release were studied. An in vitro study was performed on human fibroblast cell line HFB4 cells with aging induced by H2O2 and UV radiation. Cell cycle arrest was studied and different genes (MMP3, Col1A1, Timp3, and TERT) involved in the skin aging process were selected to measure punicalagin's effect. Punicalagin succeeded in reducing the growth arrest of HFB4 cells, activated production of the Col1A1 and Timp3 genes, maintained collagen level, and lowered of MMP3. Punicalagin increased human TERT concentration in skin cells. Punicalagin is promising as a natural antioxidant to protect human skin from aging.
REVIEW | doi:10.20944/preprints202004.0532.v1
Online: 30 April 2020 (13:58:41 CEST)
The disproportionate incidences of COVID-19-related hospitalization and mortality for different age groups and various underlying health conditions is a result of a complex social predisposition to the exposure, resistance, and tolerance for the infection. Based on the observed data as well as the molecular mechanisms for viral entry and replication, cellular senescence related to aging, obesity, hypertension, and diabetes appears to be strongly correlated with the SARS-CoV-2 infections resulting in higher COVID-19 related complications and mortality. Establishing such a correlation may allow us to better explain the pathobiology as well as the differential nature of the SARS-CoV-2 infections and consider targeted control and therapeutic strategies to combat the disease.
REVIEW | doi:10.20944/preprints202102.0362.v1
Online: 17 February 2021 (10:05:38 CET)
Polyamines are nitrogen-rich polycationic ubiquitous bioactive molecules with diverse evolutionary-conserved functions. Their activity interferes with numerous genes' expression resulting in cell proliferation and signaling modulation. The intracellular levels of polyamines are precisely controlled by evolutionary-conserved machinery. Their transient synthesis is induced by heat stress, radiation, and other traumatic stimuli in a process termed the polyamine stress response (PSR). Notably, polyamine levels decline gradually with age; and external supplementation improves lifespan in model organisms. This corresponds to cytoprotective and reactive oxygen species scavenging properties of polyamines. Paradoxically, age-associated neurodegenerative disorders are characterized by an upsurge in polyamine levels, indicating polyamine pleiotropic, adaptive, and pathogenic roles. Specifically, arginase overactivation and arginine brain deprivation have been shown to play an important role in Alzheimer’s disease (AD) pathogenesis. Here, we assert that a universal short-term PSR associated with acute stimuli is beneficial for survival. However, it becomes detrimental and maladaptive following chronic noxious stimuli, especially in an aging organism. Furthermore, we regard cellular senescence as an adaptive response to stress and suggest that PSR plays a central role in age-related neurodegenerative diseases' pathogenesis. Our perspective on AD proposes an inclusive reassessment of the causal relationships between the classical hallmarks and clinical manifestation. Consequently, we offer a novel treatment strategy predicated upon this view and suggest fine-tuning of arginase activity with natural inhibitors to preclude or halt the development of AD-related dementia.
ARTICLE | doi:10.20944/preprints202007.0741.v1
Online: 31 July 2020 (09:55:18 CEST)
Loss of muscle mass and strength are progressing with aging. Exercise is a beneficial method to prevent physical disfunction and habitual exercise improve the muscle quality. Therefore, we evaluated the effects of a long-term habitual exercise on the senescence-accelerated mice prone8 (SAMP8). 27wk SAMP8 were used in this study. Mice were classified into 28 (28w) and 44 weeks old. The 44-week group was divided into the sedentary group (44w) and a group exercising for 16 weeks (44w+Ex). The 44w+Ex performed habitual exercise from 28 to 44 weeks. Additionally, grip strength tests were performed with mice aged 28 and 44 weeks. Mice were dissected and collected muscle samples and measured muscle weight at 44w. Gastrocnemius was decreased in 44w but were unchanged in 44w+Ex. Grip strength in 44w was lower trend, but there was no change in 44w+Ex. The phosphorylation levels of Akt and p70S6K as a protein synthesis marker were decreased in 44w. Cytochrome c oxidase subunit IV(COXIV) mRNA and protein levels decreased in 44w. These results suggested that long-term habitual exercise attenuated muscle mass and strength decline through improving muscle protein synthesis and mitochondrial function. In conclusion, long-term habitual exercise attenuated muscle mass and strength decline.
ARTICLE | doi:10.20944/preprints202007.0672.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: aging; telomeres; senescence; mortality; disease
Online: 28 July 2020 (10:07:22 CEST)
The last 20 years have seen a surge in scientific activity and promising results in the study of aging and longevity. Many researchers have focused on telomeres, which are composed of a series of TTAGGG repeat nucleotide sequences at the ends of each chromosome. Measurements of the length of these telomere strands show that they decrease in length with increasing age, leading many authors to propose that when the length of these telomere strands decreases sufficiently, the cells enter into a state of replicative senescence, eventually leading to disease and death. These ideas are supported by evidence that short telomere length is correlated with increased mortality. In this paper, we extend this idea to make an actual calculation of the predicted mortality rate caused by short telomere length induced senescence (STLIS). We derive a simple equation for the mathematical relationship between telomere length and mortality rate. Using only 3 parameters based on telomere length measurement data of Canadians, we have calculated both the magnitude and the age dependence of the mortality rate, for both men and women. We show that these calculated data are in good quantitative agreement with the actual number of Canadians that die. This agreement provides strong evidence (but not proof) that the mechanism of STLIS plays an important role in the major diseases of aging (e.g., cardiovascular disease, many cancers, and diabetes mellitus) which dominate human mortality. This result represents significant progress in our understanding the factors behind the cause of aging.
ARTICLE | doi:10.20944/preprints202007.0146.v1
Online: 8 July 2020 (11:03:10 CEST)
Fenugreek seeds are widely used in Asia and other places of the world for their nutritive and medicinal properties. In Asia, Fenugreek seeds are also widely recommended for the geriatric populations. Here, we evaluated for the first time the effect of fenugreek seed feed supplementation on the liver antioxidant defense systems in aging mice. The study was conducted on 12 months aged mice which were given fenugreek seed dietary supplement. We have evaluated the activities of various antioxidant defense enzymes like superoxide dismutase (SOD), glutathione reductase (GR), and glutathione peroxidase (GPx), and estimated the phenolics and free radical scavenging properties in mice liver upon fenugreek supplementation. The estimation of SOD, GPx and GR activities in aged mice liver revealed a significant (P<0.01) difference among all the liver enzymes. Overall, this study reveals that fenugreek seed dietary supplementation has a positive effect in on the activities of the hepatic antioxidant defense enzymes in the aged mice.
REVIEW | doi:10.20944/preprints202009.0539.v1
Subject: Medicine & Pharmacology, Clinical Neurology Keywords: brain aging; energy metabolism; neurodegeneration; neurodegenerative disorders
Online: 23 September 2020 (04:55:21 CEST)
A growing body of evidence indicates that aging of the brain is strictly related to the decline of energy metabolism. In particular, in older adults, the neuronal metabolism of glucose declines steadily resulting in a growing deficit of ATP production. The decline is evoked by deficient NAD recovery in the salvage pathway and subsequent impairment of the Krebs cycle. NAD deficit impairs also the activity of NAD-dependent enzymes. All these open vicious circles of neurodegeneration and neuronal death. Some brain structures are particularly prone to aging and neurodegeneration. These are pathological foci of neurodegenerative diseases such as Alzheimer’s and Parkinson’s disease. This review article summarizes the impacts and mutual relationships between metabolic processes both on neuronal and brain levels. It also provides directions on how to reduce the risk of neurodegeneration and protect the elderly against neurodegenerative diseases.
ARTICLE | doi:10.20944/preprints201810.0510.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: limits of stability; coactivation; EMG signal; falls; aging
Online: 22 October 2018 (16:07:16 CEST)
The results of this study offer a potential to gain a better understanding of the mechanisms underlying the falls in the elderly. The results were recorded for a group of 27 women in a control group (CON) and 16 women in an experimental group (EXP), aged 60-70. Participants took part in the six-weeks Elderly Recreation Movement Program (ERMP) with the difference, that the EXP group practiced twice as often as the CON group. The measurement of variations in the index called limits of stability (LOS) was performed by application of Kistler force plate and the coactivation index (CI) was registered by means of sEMG. The results demonstrate the existence of statistically significant differences in terms of the principal outcome of the exercise time in the measurements of LOS (F (1.42) = 10.0, p = 0.003), and CI (F (1.42) = 10.5, p = 0.002). The effect of the program was associated with an increase the level of the maximum LOS, and a decrease of the CI level, especially in the experimental group. Hence, the implementation of an innovative ERMP exercise program results in the improvement of the physical capabilities of senior subjects and a reduction of the risk of falls.
ARTICLE | doi:10.20944/preprints202208.0424.v1
Subject: Behavioral Sciences, Clinical Psychology Keywords: Aging; Attitudes; Subjective Well-being; Ageism; Psychometric Validation
Online: 25 August 2022 (03:17:06 CEST)
Scientific literature shows increased interest in the aged and the aging phenomenon. The Aging Attitudes Questionnaire - AAQ was validated for the Portuguese population to understand the importance of attitudes towards old age and their impact on the subjective well-being of the elderly. A sample of 400 subjects (from 18 to 93 years) answered a socio-demographic questionnaire, and the AAQ was composed of three subscales (psychosocial losses, physical change, and psychological growth). The CFA confirmed the tri-factorial structure with very good adjustment of the model to the data with the Cronbach alpha of the total scale scoring .84 and ranging from .65 to .77 for each factor. A total of 9 items were omitted both for poor factor loadings (<0.50. Notwithstanding, 3 items below the criteria were maintained, as they conceptually fit into the factor. Of the final 15 AAQp items, 5 belong to the Psychosocial Loss factor, 6 to Physical Change, and 4 to Psychosocial Growth. This tree factor model explained 50.1 % of the total variance. In conclusion, this study supports that AAQ has acceptable validity, confirming the composite reliability and the discriminant validity, but not the convergent validity. Through multi-group analysis, the invariance of the scale was confirmed. This validation is of pivotal importance once it allows measuring the attitudes towards aging, thus facilitating the promotion of wellbeing across the lifespan.
REVIEW | doi:10.20944/preprints202106.0701.v1
Subject: Biology, Anatomy & Morphology Keywords: retina; neurodegeneration; AMD; aging; neurogenesis; development; transcription factor
Online: 29 June 2021 (12:41:56 CEST)
Age-related macular degeneration (AMD) is a complex, multifactorial neurodegenerative disease that constitutes the most common cause of irreversible blindness in the elderly in developed countries. Incomplete knowledge about its pathogenesis prevents the search for effective methods of prevention and treatment of AMD, primarily its “dry” type, which is by far the most common (90% of all AMD cases). In recent years, AMD became younger: late stages of the disease are now detected in relatively young people. It is known that AMD pathogenesis—according to the age-related structural and functional changes in the retina—is linked with inflammation, hypoxia, oxidative stress, mitochondrial dysfunction, and an impairment of neurotrophic support, but the mechanisms that trigger the conversion of normal age-related changes to the pathological process as well as the reason for early AMD development remain unclear. In the adult mammalian retina, de novo neurogenesis is very limited. Therefore, the structural and functional features that arise during its maturation and formation can exert long-term effects on further ontogenesis of this tissue. The aim of this review is to discuss possible contributions of the changes/disturbances in retinal neurogenesis to the early development of AMD.
ARTICLE | doi:10.20944/preprints202203.0380.v1
Subject: Biology, Entomology Keywords: Exercise training; arrhythmias; Drosophila; apolipoprotein B; aging
Online: 29 March 2022 (10:07:13 CEST)
Cardiovascular disease (CVD) places a heavy burden on older patients and the global healthcare system. A large body of evidence suggests that exercise training is essential in preventing and treating cardiovascular disease, but the underlying mechanisms are not well understood. Here, we used the Drosophila melanogaster animal model to study the effects of early-life exercise training (ELET) on the aging heart and lifespan. We found in flies that age-induced arrhythmias are conserved across different genetic backgrounds. The fat body is the primary source of circulating lipoproteins in flies. Inhibition of fat body apoLpp (the flies apoB homolog) demonstrated that low expression of apoLpp reduced the development of arrhythmias in aged flies but did not affect average lifespan. At the same time, ELET can also reduce the expression of apoLpp mRNA in aged flies and have a protective effect on the heart, which is similar to the inhibition of apoLpp mRNA. Although treatment of apoLppRNAi and ELET alone had no significant effect on lifespan, the combination of apoLppRNAi and ELET extended the average lifespan of flies. Therefore, we conclude that apoLppRNAi and ELET are sufficient to resist age-induced arrhythmias, which may be related to the decreased expression of apoLpp mRNA, and that apoLppRNAi and ELET have a combined effect on prolonging the average lifespan.
BRIEF REPORT | doi:10.20944/preprints202211.0215.v1
Online: 11 November 2022 (03:53:06 CET)
Aging is a complex biological process, with gradual and progressive decline in structure and function in many organ systems. Our objective is to determine if structural changes produced by aging, vary with sex, in a stressful situation such as dehydration. The expression of Slc12a3 mRNA in renal cortex, α-smooth muscle actin (α-SMA) and fibronectin, was evaluated in male and female rats aged 3 and 18 months submitted or not to water deprivation (WD) for 48 hours. When comparing ages, 18-month-old males showed lower expression of Slc12a3 mRNA than 3-month-old males, and control and WD 18-moth-old male and female rats exhibited higher expression of α-SMA than respective 3-month-old rats. Fibronectin was higher in both control and WD 18-month-old males than respective 3-month-old males. In females, only control 18-month-old rats showed higher fibronectin than control 3-month-old rats. When we compared sex, control and WD 3-month-old female rats had lower expression of Slc12a3 mRNA than re-spective males. WD 18-month-old male rats presented higher expression of fibronectin and α-SMA than WD 18-month-old female rats. When we compared hydric condition, WD 18-month-old males displayed lower relative expression of Slc12a3 mRNA and higher α-SMA expression than control 18-month-old males. Aging, sex, and dehydration lead to alteration in kidney structure.
ARTICLE | doi:10.20944/preprints202111.0082.v1
Online: 3 November 2021 (14:08:46 CET)
PSD-95 (Dlg4) is an ionotropic glutamate receptor scaffolding protein essential in synapse stability and neurotransmission. PSD-95 levels are reduced during aging and in neurodegenerative diseases like Huntington’s disease (HD), and it is believed to contribute to synaptic dysfunction and behavioral deficits. However, the mechanism responsible for PSD-95 dysregulation under these conditions is unknown. The Heat Shock transcription Factor 1 (HSF1), canonically known for its role in protein homeostasis, is also depleted in both aging and HD. Synaptic protein levels, including PSD-95, are influenced by alterations in HSF1 levels and activity, but the direct regulatory relationship between PSD-95 and HSF1 has yet to be determined. Here, we showed that HSF1 chronic or acute depletion in cell lines and mice decreased PSD-95 expression. Furthermore, HSF1(+/-) mice had reduced PSD-95 synaptic puncta that paralleled a loss in thalamo-striatal excitatory synapses, an important circuit disrupted early in HD. We demonstrated that HSF1 binds to regulatory elements present in the PSD-95 gene and directly regulates PSD-95 expression. HSF1 DNA-binding on the PSD-95 gene was disrupted in an age-dependent manner in WT mice and worsened in HD cells and mice, leading to reduced PSD-95 levels. These results demonstrate a direct role of HSF1 in synaptic gene regulation that has important implications in synapse maintenance in basal and pathological conditions.
REVIEW | doi:10.20944/preprints202102.0127.v1
Subject: Life Sciences, Biochemistry Keywords: Osteoporosis; Senescence; SASP; Aging; Radiation; Senotherapeutic
Online: 3 February 2021 (17:00:00 CET)
Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Pharmacological and genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Senescent cells have an altered secretome, which may have an autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton. The review was written following an extensive literature survey of published studies, mostly excluding articles published on pre-print servers. The review discusses potential therapeutics targeting cellular senescence and the senescent secretome as underlying pathogenesis of an aging bone.
ARTICLE | doi:10.20944/preprints202101.0162.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: behaviour; BPSD; cognitive decline; aging; SAMP8.
Online: 8 January 2021 (13:48:22 CET)
Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive and cognitive states as well as molecular alterations and their relationship, demonstrating the AD-like symptoms presented in older SAMP8 males. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in three of the most important neurotrophins, such as NT3, BDNF, and NGF as well as their receptors TrkA and TrkB, were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin alterations, cognitive impairment and neuropsychiatric disorders (ND).
REVIEW | doi:10.20944/preprints202012.0079.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Mitochondria; Alzheimer’s Disease; mitophagy; neurodegeneration; aging
Online: 3 December 2020 (10:36:29 CET)
Stress mechanisms have long been associated with neuronal loss and neurodegenerative diseases. The origin of cell stress and neuronal loss likely stems from multiple pathways. These include (but are not limited to) bioenergetic failure, neuroinflammation, and loss of proteostasis. Cells have adapted compensatory mechanisms to overcome stress and circumvent death. One mechanism is mitophagy. Recent studies have implicated mitophagy in several neurodegenerative diseases and clinical trials are underway which target mitophagy pathways. Here, we review mitophagy pathways, the role of mitophagy in neurodegeneration, potential therapeutics, and the need for further study.
ARTICLE | doi:10.20944/preprints202201.0263.v1
Subject: Life Sciences, Microbiology Keywords: drug resistance; ABC transporter; efflux pump; cryptococcosis; aging
Online: 18 January 2022 (15:56:02 CET)
Cryptococcus neoformans causes meningoencephalitis in immunocompromised individuals, which is treated with Fluconazole (FLC) monotherapy when resources are limited. This can lead to azole resistance, which can be mediated by overexpression of ABC transporters, a class of efflux pumps. ABC pump-mediated efflux of FLC is also augmented in 10-generation old C. neoformans cells. Here, we describe a new ABC transporter Afr3 (CNAG_06909), which is overexpressed in C. neoformans cells of advanced generational age, that accumulate during chronic infection. The delta-afr3 mutant strain showed higher FLC susceptibility by FLC E-Test strip testing and also by a killing test that measured survival after 3 h FLC exposure. Furthermore, delta-afr3 cells exhibited lower Rhodamine 6G efflux compared to the H99 wild type cells. Afr3 was expressed in the Saccharomyces cerevisiae AD-delta strain, which lacks several drug transporters, thus reducing background transport. The AD-delta + Afr3 strain demonstrated a higher efflux with both Rhodamine 6G and Nile Red, even though the FLC MICs were not changed. Characterization of the delta-afr3 mutant revealed unattenuated growth but a prolongation (22%) of the replicative life span. In addition, delta-afr3 exhibited decreased resistance to macrophage killing and attenuated virulence in the Galleria mellonella infection model. In summary, our data indicate that a novel ABC pump Afr3p, which is upregulated in C. neoformans cells of advanced age may contribute to their enhanced FLC tolerance, by promoting drug efflux. Lastly, its role in macrophage resistance may also contribute to the selection of older C. neoformans cells during chronic infection.
ARTICLE | doi:10.20944/preprints202209.0091.v1
Subject: Life Sciences, Molecular Biology Keywords: calorie restriction; aging; inflammation; autophagy; senescence.; skeletal muscle
Online: 6 September 2022 (11:01:40 CEST)
Calorie restriction (CR), defined as a reduction of the total calorie intake of 30% to 60% without malnutrition, is the only nutritional strategy that has proven to extend lifespan, prevent or delay the onset of age-associated diseases, and delay the functional decline in a wide range of species. However, little is known about the effects of CR when started early in life. We sought to analyze the effects of CR in the skeletal muscle of young Wistar rats. For this, 3-month-old male and female rats were subjected to 40% CR or fed ad libitum for 3 months. Gastrocnemius muscles were used to extract RNA and total protein. Western blot and RT-qPCR were performed to evaluate the expression of key markers/pathways modulated by CR and affected by aging. CR decreased body and skeletal muscle weight in both sexes. No differences were found in most senescence, antioxidant, and nutrient sensing pathways analyzed. However, we found a sexual dimorphism in markers of oxidative stress, inflammation, apoptosis, and mitochondrial function in response to CR. Our data show that young female rats treated with CR exhibit similar expression patterns of key genes/pathways associated with healthy aging when compared to old animals treated with CR, while in male rats these effects are reduced. Additional studies are needed to understand how early or later life CR exerts positive effects on health- and lifespan.
REVIEW | doi:10.20944/preprints202105.0372.v1
Subject: Life Sciences, Biochemistry Keywords: Aging; Microbiome; Probiotics; Cellular senescence; SASP; Stress; Immunity
Online: 17 May 2021 (08:51:53 CEST)
The significance of diversity, composition, and functional attributes of the gut microbiota is recognized in human health and disease. Studies have also shown that the gut microbiota is related to human aging, and a causal relationship between gut microflora dysbiosis and chronic age-related disorders is also becoming apparent. Further, emerging evidence indicates that age-associated changes in the gut microbiome are predictors of human survival and longevity. Recent advances in our understanding of the cellular and molecular aspects of biological aging have revealed a cellular senescence-centric view of the aging process. However, the association between gut microbiome and cellular senescence is only beginning to be understood. The present review provides an integrative view of the emerging relationship between the gut microbiome and cellular senescence in aging and disease. Evidence relating to microbiome-mediated modulation of senescent cells, as well as senescent cells-mediated changes in intestinal homeostasis have been discussed. Unanswered questions and future research directions have also been deliberated to truly ascertain the relationship of the gut microbiome and cellular senescence for developing microbiome-based age-delaying and longevity promoting therapies.
BRIEF REPORT | doi:10.20944/preprints202107.0075.v1
Subject: Biology, Anatomy & Morphology Keywords: DNA methylation; epigenetic aging; bottlenose dolphin; chronological age
Online: 5 July 2021 (07:59:15 CEST)
Epigenetics, specifically DNA methylation, allows for estimation of animal age from blood or remotely sampled skin. This multi tissue epigenetic aging clock uses 110 longitudinal samples from 34 Navy bottlenose dolphins (Tursiops truncatus), identifying 195 cytosine-phosphate-guanine sites associated with chronological aging via leave-one-individual-out-cross-validation (R2=0.95). With a median absolute error of 2.5 years this clock improves age estimation capacity in wild dolphins, expanding conservation efforts, enabling better understanding of population demographics.
ARTICLE | doi:10.20944/preprints202007.0021.v2
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: COVID-19; metastasis; lung adenocarcinoma; smoking; aging; ACE2
Online: 6 July 2020 (10:14:03 CEST)
The recent COVID-19 outbreak in China led to a worldwide pandemic associated with a severe acute respiratory illness. A higher incidence of COVID-19 infection was demonstrated in cancer patients, including patients with lung cancer. This study was conducted to get insights into the reasons for this enhanced frequency of COVID-19 infection. Methods: Using different bioinformatic tools, the expression and methylation pattern of ACE2 and TMPRSS2 gene were analyzed in healthy and malignant tissues with a focus on lung adenocarcinoma (LUAD) and correlated to clinical parameters and smoking history. Results: ACE2 and TMPRSS2 were heterogeneously expressed across 36 healthy tissues with the highest expression in digestive, urinary and reproductive organs, while their expression was significantly lower in 36 cancer tissues. In LUAD, ACE2, but not TMPRSS2 was overexpressed, which inversely correlated to the promoter methylation. An age-dependent upregulation of ACE2 expression was found in LUAD compared to normal lung tissues. In a healthy lung, TMPRSS2 expression was dependent on sex and smoking history and downregulated in LUAD of smokers. Cancer progression was associated with decreased TMPRSS2, but unaltered ACE2 expression, while ACE2 expression in lung metastases of different cancers was higher than in metastasis of other sites. TMPRSS2, but not ACE2 expression, was associated with LUAD patients’ survival. Conclusions: Comprehensive molecular analyses revealed a heterogeneous, distinct expression and methylation profile of ACE2 and TMPRSS2 in healthy lung vs LUAD tissues across sex, age and smoking history, which is associated with clinical parameters and might have implications for COVID-19 disease.
ARTICLE | doi:10.20944/preprints202101.0262.v1
Subject: Life Sciences, Biochemistry Keywords: lifespan; aging; radioresistance; ionizing radiation; Agronaute; Piwi; Drosophila melanogaster
Online: 14 January 2021 (08:07:44 CET)
Small RNAs are essential for the coordination of many cellular processes, including the regulation of gene expression patterns, the prevention of genomic instability, and the suppression of mutagenic transposon activity. These processes determine aging, longevity, and sensitivity of cells and an organism to stress factors (particularly, ionizing radiation). The biogenesis and activity of small RNAs are provided by proteins of the Argonaute family. These proteins participate in the processing of small RNA precursors and the formation of an RNA-induced silencing complex. However, the role of Argonaute proteins in the regulation of lifespan and radioresistance remains poorly explored. We studied the effect of knockdown of Argonaute genes (AGO1, AGO2, AGO3, piwi) in various tissues on the Drosophila melanogaster lifespan and survival after the γ-irradiation at a dose of 700 Gy. In most cases, these parameters were reduced or did not change significantly in flies with tissue-specific RNA interference. Surprisingly, piwi knockdown in both the fat body and the nervous system caused a lifespan increase. But changes in radioresistance depended on the tissue in which the gene was knocked out. In addition, analysis of changes in retrotransposon levels and expression of stress response genes allowed us to determine associated molecular mechanisms.
REVIEW | doi:10.20944/preprints202111.0458.v1
Online: 24 November 2021 (13:10:22 CET)
Nicotinamide adenine dinucleotide (NAD+) is an essential molecule involved in various metabolic reactions, acting as an electron donor in the electron transport chain and as a co-factor for NAD+-dependent enzymes. In the early 2000s, reports that NAD+ declines with aging introduced the notion that NAD+ metabolism is globally and progressively impaired with time. Since then, NAD+ became an attractive target for potential pharmacological therapies aiming to boost NAD+ levels to promote vitality and protect against age-related diseases. This review summarizes and discusses a collection of studies that report the levels of NAD+ with aging in different species (i.e., yeast, C. elegans, rat, mouse, monkey, and human) to determine whether the notion that overall NAD+ levels decrease with aging stands true. We find that despite systematic claims of overall changes in NAD+ levels with aging, the evidence to support it is very limited and often restricted to a single tissue or cell type. This is particularly true in humans, where the development of NAD+ levels during aging is still poorly characterized. There is a need for much larger, preferably longitudinal, studies aimed to assess how NAD+ levels develop with aging in various tissues. This will strengthen our conclusions on NAD+ during aging and should provide a foundation for better pharmacological targeting of relevant tissues.
ARTICLE | doi:10.20944/preprints202202.0130.v1
Subject: Physical Sciences, General & Theoretical Physics Keywords: Twin paradox; Relativity; Space-time; Time dilation; Differential aging
Online: 9 February 2022 (10:20:33 CET)
Physicists have employed various approaches to solve the “paradox” and offered a consistent conclusion that the traveller twin is younger than the homebody twin. However, some authors attribute the cause of differential aging to acceleration, while others believe that acceleration should not be regarded as the source of differential aging, but frame switch is. So far there is no agreement on this issue. Actually, acceleration and frame switch should not be regarded as the source of differential aging. The author will introduce a thought experiment in which two very long spacecraft are moving in opposite directions at a speed close to the speed of light to discuss the real cause of differential aging. The author found that the real cause of differential aging in the twin “paradox” is because of the asymmetry of destination choice. People always choose their destinations in the universe rather than in spacecraft. The destinations are always stationary relative to the homebody twin and moving relative to the traveller twin. Once we choose a destination in a reference frame, the distance is the proper length in this reference frame, but the distance will contract in another moving reference frame, thus the recording time will be shorter.
ARTICLE | doi:10.20944/preprints202112.0120.v1
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: aging; NMR spectroscopy; mice; energy metabolism; fat; intestine; metabolomics
Online: 8 December 2021 (12:03:07 CET)
Energy metabolism, including alterations in energy intake and expenditure, is closely related to aging and longevity. Metabolomics studies have recently unraveled changes in metabolite composition in plasma and tissues during aging and have provided critical information to elucidate the molecular basis of aging process. However, the metabolic changes in tissues responsible for food intake and lipid storage have remained unexplored. In this study, we aimed to investigate aging-related metabolic alterations in these tissues. To fill this gap, we employed NMR-based metabolomics in several tissues, including different parts of the intestine (duodenum, jejunum, ileum) and brown/white adipose tissues (BAT, WAT) of young (9-10 weeks) and old (96-104 weeks) wild-type (mixed genetic background of 129/J and C57BL/6) mice. We further included plasma and skeletal muscle of the same mice to verify previous results. Strikingly, we found that duodenum, jejunum, ileum, and WAT do not metabolically age. In contrast, plasma, skeletal muscle, and BAT show a strong metabolic aging phenotype. Overall, we provide first insights into the metabolic changes of tissues essential for nutrient uptake and lipid storage and have identified biomarkers for metabolites that could be further explored to study the molecular mechanisms of aging.
REVIEW | doi:10.20944/preprints202003.0082.v1
Subject: Materials Science, Polymers & Plastics Keywords: ARM-IR; polymers; polymer blends; polymer aging; nanoscale characterization
Online: 5 March 2020 (04:03:23 CET)
Atomic force microscopy (AFM) has been extensively used for the nanoscale characterization of polymeric materials. The coupling of AFM with infrared spectroscope (AFM-IR) provides another advantage to the chemical analyses and thus helps to shed light upon the study of polymers. In this perspective paper, we review recent progress in the use of AFM-IR in polymer science. We describe first the principle of AFM-IR and the recent improvements to enhance its resolution. We discuss then the last progress in the use of AFM-IR as a super-resolution correlated scanned-probe IR spectroscopy for chemical characterization of polymer materials dealing with polymer composites, polymer blends, multilayers and biopolymers. To highlight the advantages of AFM-IR, we report here several results in studying crystallization of both miscible and immiscible blends as well as polymer aging. Then, we demonstrate how this novel technique can be used to determine phase separation, spherulitic structure and crystallization mechanisms at the nanoscale, which have never been achieved before. The review also discusses future trends in the use of AFM-IR in polymer materials, especially in polymer thin film investigation.
ARTICLE | doi:10.20944/preprints202005.0074.v1
Subject: Arts & Humanities, Philosophy Keywords: VR; aging effect; gender difference; control device; wayfinding strategy
Online: 5 May 2020 (11:32:12 CEST)
The application of Virtual Reality in a driving simulation is not novel, yet little is known about the use of this technology by senior populations. The effects of age, sex, control device (joystick or handlebar), and task type on wayfinding proficiency using a virtual reality (VR) driving simulation were explored. The driving experimental model involved 96 randomly recruited participants, including 48 young people and 48 seniors (split evenly by gender in each group). The experimental results and statistical analyses indicate that in a VR driving scenario task type significantly affected VR driving performance. Navigational scores were significantly higher for the straight (easy) task than for the curved (difficult) task. The aging effect was the main reason for significant and interacting effects of sex and control device. It was found that interactions between age and sex difference indicated that the young group exhibited better wayfinding performance than the senior group, and in the young group males had better performance than females. Similarly, interactions between age and control device indicated that the handlebar control device type resulted in better performance than the joystick device in the young group, but no difference was found in the senior group due to age or learning effects. Findings provide an understanding of the evaluation of the interface designs of navigational support systems, taking into consideration any effects of age, sex, control device, and task type within three-dimensional VR games and driving systems. With a VR driving simulator, seniors can test drive inaccessible products, such as electric bicycles or cars, using a computer at home.
HYPOTHESIS | doi:10.20944/preprints202204.0124.v1
Subject: Life Sciences, Molecular Biology Keywords: Senescence; EMT; NF-κB; Inflammation; Epigenetics; Aging
Online: 13 April 2022 (10:22:37 CEST)
The origin of cancer remains one of the most important enigmas in modern biology. This paper presents a hypothesis for the origin of carcinomas in which cellular aging and inflammation enable the recovery of cellular plasticity that may ultimately result in cancer. The process is described as the result of dedifferentiation undergone by epithelial cells in hyperplasia due to replicative senescence towards a mesenchymal cell state with potential cancerous behavior. In support of the hypothesis, the molecular, cellular, and histopathological evidence was critically reviewed and reinterpreted when necessary to postulate a plausible generic model for the origin and progression of carcinomas. In addition, the implications of this theoretical framework for the current strategies of cancer treatment are discussed against recent evidence of the molecular events underlying the epigenetic switches involved in the resistance of breast carcinomas. Subsequently, is proposed an epigenetic landscape for their progression and a potential mechanism to restrain the degree of dedifferentiation and malignant behavior. Finally, is suggested a novel understanding of the involution and carcinogenesis of tissues associated with aging as a perspective that might inspire integrative approaches in the study and management of chronic diseases.
REVIEW | doi:10.20944/preprints202112.0468.v1
Subject: Medicine & Pharmacology, Anesthesiology Keywords: aging; elderly; pain; opioids; dementia; cognitive impairment
Online: 29 December 2021 (13:42:02 CET)
Background: Assessment and management of pain in elderly people with cognitive impairment is particularly challenging. Physiological changes due to aging as well as comorbidities and polypharmacy are responsible for a complex clinical approach. Concomitantly, in cognitive impairment, including advanced dementia, changes in central nervous system along with changes in the peripheral nervous system due to aging have a significant impact in pain perception. Often clinicians decide to prescribe opioids in order to relief pain, also without a clear indication. Aim: This review aims to investigate the effect of opioids in elderly patients with cognitive impairment. Methods: A literature search of PubMed/Medline, Scopus, and Cochrane databases was conducted using keyword searches to generate lists of articles which were screened for relevance by title and abstract to give a final list of articles for full-text review. Further articles were identified by snowballing from the reference lists of the full-text articles. Results: This review discuss the complex physiological and pharmacological changes in elderly as well as the neurological changes that affect pain perception in this population. Additionally, it focuses on cognitive impairment and pain in Alzheimer’s disease and other dementias, the pain assessment in the elderly with cognitive impairment as well as the safety of opioid use in elderly. Information regarding opioid prescription in nursing homes as well as recorded indications for opioids use, type and dosing of opioid and compliance of treatment in advanced dementia are also provided. Conclusions: Opioid prescription in elderly population with cognitive impairment is particularly complex. All healthcare professionals involved in the care of such patients, need to be aware of the challenges and strive to ensure analgesic use is guided by appropriate and accurate pain assessment.
ARTICLE | doi:10.20944/preprints202111.0387.v1
Subject: Medicine & Pharmacology, Other Keywords: Aging; Accidental Falls; Frail Elderly; Postural Balance
Online: 22 November 2021 (11:50:39 CET)
This study aimed to characterize the risk of falling in low, moderate and high risk participants from two different geographical locations using a portable force-plate. A sample of 390 older adults from South and North America were matched for age, sex, height and weight. All participants performed a standardized balance assessment using a force plate. Participants were classified in low, moderate and high risk of falling. No differences were observed between South and North American men, nor comparing North American men and women. South American women showed the significantly shorter center of pressure path length compared to other groups. The majority of the sample was categorized as having low risk of falling (male: 65.69 % and female: 61.87 %), with no differences between men and women. Also, no differences were found between North vs. South Americans, nor for falls risk levels when male and female groups were compared separately. In conclusion, South American women had better balance compatible with the status of the 50-59 years’ normative age-range. The prevalence of low falls risk was ~ 61-65 % and the prevalence of moderate to high risk was ~ 16-19 %. The frequency of fall risk did not differ significantly between North and South Americans, nor between males and females.
REVIEW | doi:10.20944/preprints202102.0491.v1
Subject: Biology, Anatomy & Morphology Keywords: mTORC1; mTORC2; rapamycin; rapalog; aging; lifespan; longevity
Online: 22 February 2021 (15:34:25 CET)
Inhibition of mTORC1 (mechanistic Target Of Rapamycin Complex 1) signaling promotes health and longevity in diverse model organisms. Over the past decade, excitement has built over the possibility that treatment with the mTORC1 inhibitor rapamycin can be utilized to treat or prevent age-related disease in humans. However, concerns over the side effects of rapamycin on immunity and metabolism have precluded the routine use of rapamycin as a geroprotective therapy. Here, we discuss the evidence that these negative side effects of rapamycin are largely mediated by off-target inhibition of a second mTOR Complex (mTORC2). Further, we discuss how intermittent treatment with rapamycin, specific dietary regimens, and new molecules may provide routes to the safer and more selective inhibition of mTORC1. We conclude that the time is ripe for the development of therapies based on the safe and selective inhibition of mTORC1 for the treatment or prevention of diseases of aging.
ARTICLE | doi:10.20944/preprints202011.0336.v1
Subject: Medicine & Pharmacology, Allergology Keywords: behaviour; BPSD; cognitive decline; aging; correlations; SAMP8
Online: 12 November 2020 (09:46:48 CET)
Alzheimer’s disease (AD) is characterized by cognitive impairment and different non-cognitive deficits called “Behavioural and psychological symptoms of dementia” (BPSD) related to neurotrophin alterations, which differ from those presented in normal aging. Mouse models, both transgenics and inbreed mice models of AD, are a useful tool in understanding the underlying mechanisms of the disease. The SAMP8 (senescence-accelerated mouse prone 8) mice line was generated from AKR/J strain by Professor Toshio Takeda at the University of Kyoto. This strain exhibited a particular early-onset and accelerated aging phenotype. The present study characterizes and provides information regarding the non-cognitive, cognitive and neurotrophin alterations and their correlation, demonstrating the AD-like symptoms presented in older males SAMP8. The cognitive impairment presented was accompanied by a reduction in sociability and an increase in aggressive as well as anxiety behaviours. Furthermore, changes in two of the most important neurotrophins, such as brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3) were found. Thus, the present results reveal new insights in this useful inbred mouse model of neurodegeneration and AD, demonstrating the potential relationship between neurotrophin modifications, cognitive impairment and neuropsychiatric disorders (ND).
ARTICLE | doi:10.20944/preprints201808.0025.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: terminology, health, aging, biological age, wellbeing, biomarker
Online: 1 August 2018 (15:00:47 CEST)
Despite increasing research efforts, there is a lack of consensus on defining aging or health. To understand the underlying processes, and to foster the development of targeted interventions towards increasing one’s health, there is an urgent need: (1) to find a broadly acceptable and useful definition of health, based on a list of features (which may or may not be molecular); (2) to operationalize features of health so that it can be measured; (3) to identify predictive biomarkers and (molecular) pathways of health, and (4) to suggest interventions, such as nutrition and exercise, targeted at putative causal pathways and processes. Based on a survey of the literature, we propose to define health as a state of an individual characterized by the core features of (a) physiological function, (b) cognitive function and (c) physical function, amended, specifically in case of humans, by (d) lack of disease, and by (e) reproductive function. Often used concepts such as lack of frailty, allostatic load, or self-reported health (in case of human), and indices such as the Healthy Aging Index can be viewed as projections or surrogates of our definition. We further define aging as the set of all processes in an individual that reduce its “wellbeing”, that is, its health or survival or both. We define biomarkers of health by their attribute of predicting future health better than chronological age. We define healthspan pathways as molecular features of health that relate to each other, specifically by belonging to the same molecular pathway. Our conceptual framework may integrate diverse operationalizations of health and guide precision prevention efforts that are a key to reducing the need for medical and nursing care.
REVIEW | doi:10.20944/preprints201712.0023.v2
Subject: Life Sciences, Endocrinology & Metabolomics Keywords: physical exercise; irisin; neurodegeneration; aging; Alzheimer’s disease
Online: 11 February 2018 (04:28:07 CET)
Irisin, a skeletal muscle-secreted myokine, produced in response to physical exercise, has protective functions in both the central and the peripheral nervous systems, including the regulation of brain-derived neurotrophic factors and modification of telomere length. Such beneficial effects may inhibit or delay the emergence of neurodegenerative diseases, including Alzheimer’s disease (AD). This review is based on the hypothesis that irisin produced by physical exercise helps control AD progression. Herein, we describe the physiology of irisin and its potential role in delaying or preventing AD. Although current and ongoing studies on irisin show promising results, further research is required to clarify its potential as a meaningful therapeutic target for treating human diseases.
ARTICLE | doi:10.20944/preprints202010.0572.v1
Subject: Life Sciences, Biochemistry Keywords: aging; collagen; extracellular matrix; fibroblast; skin; tenascin C; TGF-β
Online: 28 October 2020 (08:49:54 CET)
Tenascin C (TNC) is an element of the extracellular matrix (ECM) of various tissues, including the skin, and is involved in modulating ECM integrity and cell physiology. Although skin aging is apparently associated with changes in the ECM, little is known about the role of TNC in skin aging. Here we found that Tnc mRNA level was significantly reduced in the skin tissues of aged mice compared with young mice, consistent with reduced TNC protein expression in aged human skin. TNC-large (TNC-L; 330-kDa) and -small (TNC-S; 240-kDa) polypeptides were observed in conditional media from primary dermal fibroblasts. Both recombinant TNC polypeptides, corresponding to TNC-L and TNC-S, increased the expression of type I collagen and reduced the expression of matrix metalloproteinase-1 in fibroblasts. Treatment of fibroblasts with a recombinant TNC polypeptide, corresponding to TNC-L, induced phosphorylation of SMAD2 and SMAD3. TNC increased the level of TGF-β1 mRNA and upregulated the expression of type I collagen by activating the TGF-β signaling pathway. In addition, TNC also promoted the expression of type I collagen in fibroblasts embedded in a three-dimensional collagen matrix. Our findings suggest that TNC contributes to the integrity of ECM in young skin and to prevention of skin aging.
REVIEW | doi:10.20944/preprints202210.0248.v1
Subject: Biology, Other Keywords: Trade-off of survival for reproduction; natural selection of aging; regulatory redundancy; aging’s individual benefit; regulatory molecular biology; Darwin’s dilemma; aging-reproduction trade-off; aging declines force of selection; master gene; holistic regulatory mechanism
Online: 18 October 2022 (04:36:09 CEST)
There is scientific consensus that organismal aging did not evolve by natural selection (NS) because it lacks individual benefit. Nonetheless it exists, leading to much speculation about its origins, and when the diminishing force of selection begins. Both concepts are based upon two misconceptions; that aging occurs in and of itself and is caused by the declining strength of NS during the reproductive lifespan. Although lacking individual benefit, aging evolved by NS as a tradeoff of survival for reproduction. Based upon regulatory dynamics that participate in this tradeoff, aging begins once reproductive success has been achieved through offspring nurturing. Thereafter, the strength of NS wanes to exponentially accelerate aging, leading to death. Assumptions of the theory are that: (1) a life-long, “holistic” regulatory mechanism whose genic expression is modified epigenetically, originates in ontogenesis; (2) the regulatory mechanism of the last developmental stage becomes redundantly expressed during “morphostasis”, a non-aging, life interval of peak vitality to ensure completion of reproduction through nurturing, and (3) thereafter, loss of regulatory redundancy causes aging which reduces the strength of natural selection and allows accumulation of randomly occurring somatic damage.
ARTICLE | doi:10.20944/preprints202007.0173.v1
Subject: Materials Science, Other Keywords: Al-Zn-Mg alloy; Retrogression re-aging treatment; Corrosion; Electrochemistry
Online: 9 July 2020 (07:34:27 CEST)
The effect of retrogression re-aging treatment (RRA) on corrosion behavior of 7055 Al-Zn-Mg alloy were studied. Results provides the corrosion resistance could be greatly improved by RRA. After the RRA treatment, the isolated precipitates occurred on grain boundaries (GBs) and the low angle grain boundaries (LAGBs) presented a larger fraction compared to the single-stage peaking aging. The samples after RRA treatment also show better corrosion resistance than the single-stage peak aging. The results of electrochemical impedance spectroscopy (EIS) show that impedance spectrum is consisted of semi-infinite layer diffusion impedance and stagnant Weber impedance. The semi-infinite layer diffusion impedance corresponded a limited retention layer on the electrode surface. In corrosion process, Weber impedance corresponded to stagnant layer of corrosion products generated by the anode branches. The RRA sample has the high Rf and low Cf, Cp values, and the corrosion current density of the RRA samples is ten times less than the single-stage peak aging samples with the 10% hardness losing.
REVIEW | doi:10.20944/preprints202005.0388.v1
Subject: Biology, Other Keywords: GDNF; SOX1; CAFs; senescence; aging cell; methylation; tumour; glioma
Online: 24 May 2020 (16:53:56 CEST)
The extrinsic and intrinsic factors are essential in glioma initiation. Many extrinsic factors (UV, radiation, food, etc.) and intrinsic factors (proteins, hormones, ageing, DNA and RNA damages, etc.) was reported to being responsible for glioma initiation and progression. However, the cell responsible for glioma origin is still unknown. Many research papers have reported that glioma stem cells, senescent cells, injured cells, and death neurons are the cells of glioma origin. However, gene mutation and oncogene protein overexpression doesn’t occur only in cancer but during life evolution. The source of genetic mutations has become a fundamental issue in understanding its role in the initiation of glioma. The glioma is the precise coordination of several distant factors that work together in the initiation and development of glioma. However, the role and effects of the genes (GDNF and SOX1) on cancer cells are well known, but their gene mutation origin is controversial. Several models and theories have been proposed to explain the origins of GDNF and SOX1 genetic mutations and epigenetic modification related to cancer. Our aim in this review is to clear that incertitude about glioma origin (gene mutation and epigenetic modifications) and those factors involved in glioma initiation and recurrence.
ARTICLE | doi:10.20944/preprints201812.0359.v1
Subject: Materials Science, Metallurgy Keywords: Inconel; high temperature; tensile test; creep; serrated; dynamic strain aging
Online: 31 December 2018 (09:41:56 CET)
Abstract: The Inconel 625 is a nickel-based alloy has been widely used in the high-temperature application. The Inconel 625 exhibits unstable plastic flow at elevated temperature characterized by serrated yielding, known as Portevin-Le Chatelier effect. The aim of this work is to evaluate the mechanical properties at high temperatures of the Inconel 625. The tensile tests were performed in the temperature range of room temperature until 1000 °C and strain rate of 2x10^-4 to 2x10^-3 s^-1. The creep tests were performed in the temperature range of 600-700 °C, in the stress range of 500-600 MPa in a constant load mode. The surface fracture was observed by optical and scanning electron microscopy. Serrated stress-strain behavior was observed in the curves obtained at 200 to 700 °C, which was associated with the dynamic strain aging effect. The yield strength and the elongation values show an anomalous behavior as a function of the test temperature. An intergranular cracking was observed specimen tensile tested at 500 °C that can be attributed to the decohesion of the carbides along the grain boundaries. The fracture surface of the specimen tensile tested at 700 °C showed the predominance of transgranular cracking with tear dimples with a parabolic shape.
ARTICLE | doi:10.20944/preprints201904.0120.v1
Subject: Medicine & Pharmacology, Sport Sciences & Therapy Keywords: mixed reality headset; mobility assessment; wearable sensor; fall risk; aging
Online: 10 April 2019 (08:33:16 CEST)
Functional mobility assessments (i.e., Timed Up and Go) are commonly used clinical tools for mobility and fall risk screening in the aging population. In this work, we proposed a new Mixed Reality (MR)-based assessment that utilized a Microsoft HoloLensTM headset to automatically lead and track the performance of functional mobility tests, and subsequently evaluated its validity in comparison with reference inertial sensors. Twenty-two healthy adults (10 older, 12 young) participated in this study. An automated functional mobility assessment app was developed based on the HoloLens platform. Mobility performance was recorded with the headset built-in sensor and validated with reference inertial sensor (Opal, APDM) taped on the headset and lower back. Results indicate vertical kinematic measures by HoloLens was in good agreement with the reference sensor (Normalized RMSE ~ 10%). Additionally, the HoloLens-based test completion time was in perfect agreement with clinical standard stopwatch measure. Overall, our preliminary investigation indicates that it is possible to use an MR headset to automatically guide users to complete common mobility tests with good measurement accuracy, thus it has great potential to provide objective and efficient sensor-based mobility assessment.
ARTICLE | doi:10.20944/preprints201904.0163.v1
Subject: Materials Science, Polymers & Plastics Keywords: polymer aging; swelling behavior; protective glove materials; elastomers; composites; rubber
Online: 15 April 2019 (11:29:10 CEST)
Butyl rubber-based composite (BRC) is one of the most popular materials for the fabrication of protective glove against chemical and mechanical risks. However, in many working places such as metal manufacturing or automotive mechanical services, its mechanical hazards usually appear together with metalworking fluids (MWFs). The presence of these contaminants, particularly at high temperature, could modify its properties due to the scission, the plasticization, the crosslinking of polymer network and thus led to severe modification of mechanical and physicochemical properties of material. This work aims to determine the effect of temperature and a metalworking fluid on mechanical behavior of butyl rubber composite dealing with crosslinking density, cohesion forces and elastic constant of BRC on the based on Mooney-Rivlin’s theory. The effect of temperature with and without MWFs on thermo dynamical properties and morphology of butyl membranes is also investigated. The prediction of service lifetime is then evaluated from extrapolation of Arrhenius plot at different temperatures.
ARTICLE | doi:10.20944/preprints202012.0683.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: transcranial direct current stimulation; true recognition; false recognition; aging; experiment.
Online: 28 December 2020 (11:15:38 CET)
Background. False memories tend to increase in healthy and pathological aging, and their reduction could be useful in improving cognitive functioning. The objective was to use an active-placebo method to verify whether the application of tDCS in improving true recognition and reducing false memories in healthy older people. Method. Participants were 29 healthy older adults (65-78 years old) assigned to active or placebo group; active group received anodal stimulation at 2mA for 20 min over F7. An experimental task was used to estimate true and false recognition. The procedure took place in two sessions on two consecutive days. Results. A mixed ANOVA of true recognition showed a significant main effect of session (p = .004), indicating an increase from before treatment to after it. False recognition showed a significant main effect (p = .004), indicating a decrease from before treatment to after it and a significant session x group interaction (p < .0001). Conclusions. Overall, our results show that tDCS is an effective tool for increasing true recognition and reducing false recognition in healthy older people, and suggest that stimulation improves recall by increasing the number of items a participant can recall and reducing the number of memory errors.
TECHNICAL NOTE | doi:10.20944/preprints202009.0168.v1
Subject: Mathematics & Computer Science, General & Theoretical Computer Science Keywords: lung function; epigenetic aging; machine learning; feature selection; hyperparamter tuning
Online: 8 September 2020 (03:15:28 CEST)
Epigenetic aging has been found associated with a number of phenotypes and diseases. Few studies investigated its effect on lung function in relatively older people. However, this effect has not been explored in younger population. This study examines whether lung function at adolescent can be predicted with epigenetic age accelerations (AAs) using machine learning techniques. DNA methylation based AAs were estimated in 326 matched samples at two time points (at 10 years and 18 years) from the Isle of Wight Birth Cohort. Five machine learning regression models (linear, lasso, ridge, elastic net, and Bayesian ridge) were used to predict FEV1 (Forced Expiratory Volume in one second) and FVC (Forced Vital Capacity) at 18 years from feature selected predictor variables (based on mutual information) and AA changes between the two time points. The best models were ridge regression (R2 = 75.21% ± 7.42%; RMSE = 0.3768 ± 0.0653) and elastic net regression (R2 = 75.38% ± 6.98%; RMSE = 0.445 ± 0.069) for FEV1 and FVC, respectively. This study suggests that the application of machine learning in conjunction with tracking changes in AA over life span can be beneficial to assess the lung health in adolescence.
HYPOTHESIS | doi:10.20944/preprints202108.0267.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: Cancer dormancy; Low-grade chronic inflammation; Healthy aging; Physical exercise
Online: 11 August 2021 (17:57:09 CEST)
The paradigm of the Somatic Mutation Theory (SMT) is failing and a new paradigm is in the making but not yet established. What is being challenged is a conceptual approach that involves the entire human biology and the development of chronic diseases. The behavior of breast cancer is well compatible with the concept that the primary tumor is able to control its microscopic metastases, in the same way that an organ (e.g., the liver) is able to control its physiological size. This finding suggested that breast cancer and its metastases may behave as an organoid. The new paradigm under construction considers the origin of tumors as a disturbance in the communication network between tissue cell populations and between cells and extracellular matrix, and supports a systemic approach to the study of both healthy and pathologic tissues. The commentary provides a rationale for the role of physical exercise in the control of tumor dormancy according to a human evolutionary perspective.
ARTICLE | doi:10.20944/preprints201912.0338.v2
Subject: Materials Science, General Materials Science Keywords: aluminum alloys; artificial aging; drilling; surface quality; cutting fluid; burr formation
Online: 27 March 2020 (02:54:29 CET)
This article discuss the effects of heat treatment and lubrication modes on the machinability of an A356 alloy (Al-Si-Mg); the alloy is studied as-received, with solution heat-treated alloy (SHT) as well as with an alloy that is solution heat-treated and then aged at 155, 180 and 220 °C. In the course of machinability evaluation, several criteria including cutting force, surface roughness, tool wears and burr analysis (chip) were studied. The results and analysis in this work indicated that the selected machinability criteria are important and necessary to effectively evaluate the machinability of A356 alloys. The machinability of both materials and tools were estimated in terms of cutting force, chip thickness ratio and burr formation, flank wear and roughness. The effects of different cutting parameters (cutting speed and feed rate) and lubrication modes (dry, mist and wet) on the machinability of the A356 cast alloy were also examined. The influence of heat treatments on the burr formation and surface quality was clearly revealed by the experimental results. Experimental work revealed that cutting forces were influenced significantly by aging and cutting speed. However, the different aging at 155, 180, and 220 °C and the cutting speed significantly affected the machinability of the A356 cast alloy. The results obtained show that a better drilling performance in terms of surface quality occurs at a high feed rate, with dry drilling and artificial aging at T6.
ARTICLE | doi:10.20944/preprints202209.0377.v1
Subject: Biology, Physiology Keywords: aging; immunosenescence; physical fitness; physical activity; obesity; sex
Online: 26 September 2022 (05:00:15 CEST)
Cardiorespiratory fitness (CRF) is essential for sustained work ability in good health, but declines with aging as does the functionality of the immune system, the latter process commonly referred to as immunosenescence. This study aimed to compare the capacity of immunosenescence biomarkers with chronological age for predicting low CRF in a cross-sectional sample recruited from the regional working population. CRF was determined by submaximal bicycle ergometer testing in a cross-sectional sample of 597 volunteers aged 20–70 years from the ’Dortmund Vital Study’ (DVS, ClinicalTrials.gov Identifier: NCT05155397). Low CRF was scored, if the ergometer test was not completed due to medical reasons or if the power output projected to a heart rate of 130 bpm divided by body mass was below sex-specific reference values of 1.25 W/kg for females and 1.5 W/kg for males, respectively. In addition to established biomarkers of immunosenescence, we calibrated a comprehensive metric of immune age to our data and compared its predictive capacity for low CRF to chronological age while adjusting our analysis for the influence of sex, obesity, and level of regular physical activity by applying univariate and multiple logistic regression. While obesity, low physical activity, chronological and immune age were all associated with increased probability for low CRF in univariate analyses, multiple logistic regression revealed that obesity and physical activity together with immune age, but not chronological age, were statistically significant predictors of low CRF outcome. Sex was non-significant due to the applied sex-specific reference values. These results demonstrate that biological age assessed by our immunological metric can outperform chronological age as a predictor for CRF and indicate a potential role for immunosenescence in explaining the inter-individual variability of the age-related decline in cardiorespiratory fitness.
ARTICLE | doi:10.20944/preprints202202.0208.v1
Subject: Biology, Physiology Keywords: aging; intestinal microbiota; dysbiosis; probiotics; microbial co-occurrences
Online: 17 February 2022 (10:59:55 CET)
Age-related alterations in the gut microbiome composition and its impacts on the host’s health have been well described; however, detailed analyses of the gut microbial structure defining ecological microbe-microbe interactions is limited. One of the ways to determine these interactions is by understanding microbial co-occurrence patterns. We previously showed promising abilities of Lactobacillus acidophilus DDS-1 on the aging gut microbiome and immune system. However, the potential of the DDS-1 strain to modulate microbial co-occurrence patterns is unknown. Hence, we aimed to investigate the ability of L. acidophilus DDS-1 to modulate the fecal, mucosal and cecal-related microbial co-occurrence networks in young and aging C57BL/6J mice. Our Kendall’s tau correlation measures of co-occurrence revealed age-related changes in the gut microbiome, which were characterized by reduced number of nodes and associations across sample types when compared to younger mice. After four-week supplementation, L. acidophilus DDS-1 differentially modulated the overall microbial community structure in fecal and mucosal samples as compared to cecal samples. Beneficial bacteria such as Lactobacillus and Akkermansia acted as connectors in aging networks in response to L. acidophilus DDS-1 supplementation. Our findings provided the first evidence of the DDS-1-induced gut microbial ecological interactions revealing the complex structure of microbial ecosystems with age.
ARTICLE | doi:10.20944/preprints202104.0542.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: action unit; aging; emotion; facial expression; facial recognition
Online: 20 April 2021 (12:47:43 CEST)
The ability to express and recognize emotion via facial expressions is well known to change with age. The present study investigated the differences in the facial recognition and facial expression of the elderly (n = 57) and the young (n = 115) and measure how each group uses different facial muscles for each emotion with Facial Action Coding System (FACS). In facial recognition task, the elderly did not recognize facial expressions better than young people and reported stronger feelings of fear and sad from photographs. In making facial expression task, the elderly rated all their facial expressions as stronger than the younger, but in fact, they expressed strong expressions in fear and anger. Furthermore, the elderly used more muscles in the lower face when making facial expressions than younger people. These results help to understand better how the facial recognition and expression of the elderly change, and show that the elderly do not effectively execute the top-down processing concerning facial expression.
ARTICLE | doi:10.20944/preprints201910.0305.v1
Online: 27 October 2019 (11:04:31 CET)
Collagen type I production decreases with aging, leading to wrinkles and impaired skin function. Prostaglandin E2 (PGE2), a lipid-derived signaling molecule produced from arachidonic acid by cyclo-oxygenase, inhibits collagen production and induces matrix metallopeptidase 1 (MMP1) expression by fibroblasts in vitro. PGE2-induced collagen expression inhibition and MMP1 promotion are aging mechanisms. This study investigated the role of E-prostanoid 1 (EP1) in PGE2 signaling in normal human dermal fibroblasts (NHDFs). When EP1 expression was inhibited by EP1 small interfering RNA (siRNA), there were no significant changes in messenger RNA (mRNA) levels of collagen, type I, alpha 1 (COL1A1)/MMP1 between siRNA-transfected NHDFs and siRNA-transfected NHDFs with PGE2. This result showed that EP1 is a PGE2 receptor. Extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation after PGE2 treatment significantly increased by ~2.5 times. In addition, PGE2 treatment increased the intracellular Ca2+ concentration in NHDFs. These results indicated that PGE2 is directly associated with EP1 pathway–regulated ERK1/2 and inositol trisphosphate (IP3) signaling in NHDFs.
Subject: Behavioral Sciences, Cognitive & Experimental Psychology Keywords: eyetracking, eye movements, gaze, memory, retrieval, vision, aging
Online: 20 May 2019 (12:25:44 CEST)
Eye movements support memory encoding by binding distinct elements of the visual world into coherent representations. However, the role of eye movements in memory retrieval is less clear. We propose that eye movements play a functional role in retrieval by reinstating the encoding context. By overtly shifting attention in a manner that broadly recapitulates the spatial locations and temporal order of encoded content, eye movements facilitate access to, and reactivation of, associated details. Such mnemonic gaze reinstatement may be obligatorily recruited when task demands exceed cognitive resources, as is often observed in older adults. We review research linking gaze reinstatement to retrieval, describe the neural integration between the oculomotor and memory systems, and discuss implications for models of oculomotor control, memory, and aging.
ARTICLE | doi:10.20944/preprints202102.0091.v1
Subject: Medicine & Pharmacology, Nursing & Health Studies Keywords: Frailty; Social Isolation; Social Networks; Social Support; Social Participation; Aging
Online: 2 February 2021 (14:32:33 CET)
This research investigated the effects of social isolation on frailty and health outcomes and tested whether these associations varied across different levels of frailty. We performed a multivariate analysis of data from the first wave of the FRéLE study among 1,643 Canadian older adults aged 65 years and over. We assessed social isolation using social participation, social networks, and support from various social ties, namely, friends, children, extended family, and partner. Frailty predicted disability, comorbidity, depression, and cognitive decline. Less social participation was associated with IADLs, depression, and cognitive decline. The absence of friends was associated with depression and cognitive impairment. Less social support from children and partner was related to comorbidity, depression, and cognitive decline. Overall, social isolation is linked to mental health, rather than physical health. The associations of having no siblings, receiving less support from friends, and participating less in social activities with ADL limitations, depression, and cognitive decline were higher among frail than pre-frail and robust older adults. This study corroborates the pivotal role of social connectedness, particularly the quality of relationships, on the mental health of older adults. Public health policies on social relationships are paramount to ameliorate the health status of frail older adults.
ARTICLE | doi:10.20944/preprints202301.0374.v1
Subject: Medicine & Pharmacology, Other Keywords: Telomerase; leukocyte telomere length; vitamin D; aging; serum levels; geroscience
Online: 22 January 2023 (03:36:34 CET)
Background: Shorter leukocyte telomere length (LTL) is observed in multiple age-related diseases, which are also associated with vitamin D deficiency (i.e., osteosarcopenia, neurocognitive disorders, cancer, osteoarthritis, etc.), which suggests a close association. In this study, we examined the relationship between vitamin D levels and LTL in older participants of the UK Biobank. Methods: Data were collected from the UK Biobank. Participants aged 60 and older (n=148,321) were included. Baseline LTL was measured using a multiplex qPCR technique and expressed as the ratio of the telomere amplification product (T) to that of a single-copy gene (S) (T/S ratio). Se-rum 25-hydroxyvitamin D (25OHD) was stratified by z score and linked to LTL in a linear regression model adjusting for covariates. Results: Compared to the medium level, a low (in the range of 16.6 nmol/L, 29.7 nmol/L) or extremely low (≤ 16.6 nmol/L) level of serum 25OHD was associated with shorter LTL: 0.018 SD (standardized β= -0.018, 95% CI -0.033 to -0.003, P=0.022) and 0.048 SD (standardized β= -0.048, 95% CI -0.083 to -0.014, P=0.006), respectively. Additionally, the high serum 25OHD groups (> 95.9 nmol/L) had 0.038 SD (standardized β= -0.038, 95% CI -0.072 to -0.004, P=0.030) shorter mean LTL than the group with medium 25OHD levels. The associations above were adjusted for multiple variables. Conclusion: In this population-based study, we identified an inverted U-shape relationship between LTL and vitamin D status. Whether high or low vitamin D-associated shorter LTL is mechanistically related to age-related conditions remains to be elucidated.
ARTICLE | doi:10.20944/preprints202212.0332.v1
Subject: Materials Science, Biomaterials Keywords: Biomechanics; Orthodontic force; Torque; Tooth Movement; Removable Thermoplastic Appliance; Aging; Aligners
Online: 19 December 2022 (09:10:51 CET)
The aim of this study is to study the effect of aging in different media (deionized water and artificial saliva) on the force/torque generation by thermoplastic orthodontic aligners. Ten thermoformed aligners made of Essix ACE® thermoplastic sheets were aged in deionized water and in artificial saliva over two weeks at 37 C, five in each medium. The force/torque generated on upper second premolar (Tooth 25) of a resin model was measured at day 0 (before aging), 2, 4, 6, 10, and 14, using a biomechanical test set-up. The results showed that the thermocycling of aligners has no significant impact on their force/torque decay. No significant differences were also found in force/torque between the aligners stored in deionized water nor artificial saliva. The vertical extrusion-intrusion forces were measured in the range of 1.4 to 4.6 N, the horizontal oro-vestibular forces were 1.3 to 2.5 N, while the torques on mesio-distal rotation were 5.4 to 41.7 Nmm. It could be concluded that the influence of saliva on the mechanical properties can be classified as insignificant, and no significant difference between artificial aging in deionized water or artificial saliva was observed.
ARTICLE | doi:10.20944/preprints202202.0153.v2
Subject: Life Sciences, Other Keywords: winter mortality; trends; season; estimated influenza mortality; pandemic influenza; aging
Online: 25 February 2022 (14:24:30 CET)
Trends in excess winter mortality (EWM) were investigated from the winter of 1900/01 to 2019/20. During the 1918-1919 Spanish flu epidemic a maximum EWM of 100% was observed in both Denmark and the USA. During the Spanish flu epidemic in the USA 70% of excess winter deaths were coded to influenza. EWM steadily declined from the Spanish flu peak to a minimum around the 1970’s to 1980’s. There is evidence that this decline was accompanied by a shift in deaths away from the winter, and that the EWM calculation shifted from a maximum around April to June in the early 1900’s to around March since 1967. EWM has a good correlation with the number of estimated influenza deaths, but in this context influenza pandemics after the Spanish flu only had an EWM equivalent to that for seasonal influenza. Using data from 1980 onward the effect of influenza vaccination on EWM was examined using a large international data set. No effect of increasing influenza vaccination could be discerned; however, there are multiple competing forces influencing EWM which will obscure any underlying trend, e.g., increasing age at death, multimorbidity, dementia, polypharmacy, diabetes, and obesity – all of which either interfere with vaccine effectiveness or are risk factors for influenza death. After adjusting the trend in EWM in the USA influenza vaccination can be seen to be masking higher winter deaths among a high morbidity US population. Winter deaths are clearly the outcome of a complex system of competing long-term trends.
REVIEW | doi:10.20944/preprints202211.0255.v1
Subject: Medicine & Pharmacology, Other Keywords: Anti-aging therapy; lipofuscin; SENS; oncolytic vector; telomerase; TFEB; intracellular microbe
Online: 14 November 2022 (11:05:02 CET)
Aging kills 100,000 people a day - more than any other cause of death combined. The exact causes of aging have been much discussed, but the most pressing issue with regard to aging appears to me to be lipofuscin accumulation. That is, the accumulation of indigestible cellular garbage that needs to be removed from our cells, then the body. In this piece, I will explain why I think “getting rid of the garbage” should be at least one of our main goals with regard to longevity research for now.
REVIEW | doi:10.20944/preprints202204.0055.v1
Subject: Life Sciences, Molecular Biology Keywords: cell; biology; aging; medicine; transcription; activity; neurons; brain; immune system; muscle
Online: 7 April 2022 (04:24:23 CEST)
In several mammalian species including humans, complex stimulation patterns such as cognitive challenge and physical exercise lead to improvements in organ function, organism health and performance, as well as possibly longer lifespans. The hypothesis is presented here that activity-dependent transcriptional programs, induced by these environmental stimuli, temporarily and lightly de-differentiate somatic cells such as neurons and muscle cells into a state that resembles functionally younger cells to allow cellular remodeling and adaptation of the organism to environmental change. This cellular adaptation program targets several process classes that are heavily implicated in aging, such as mitochondrial metabolism, cell-cell communication, intracellular signaling and epigenetic information processing and leads to functional improvements in these areas. I reverse engineer these activity-dependent gene programs, identify critical molecular nexus points such as CREB, MEF2 and cFos and speculate as to how one might leverage them to prevent and attenuate human aging-related decline of body function, enhance human performance and restore more youthful levels of function and morphology. The findings presented here can serve as a basis for the study and development of effective longevity efforts as the underlying gene programs could be used as markers for treatment success and as targets for therapy development.
ARTICLE | doi:10.20944/preprints202205.0061.v1
Subject: Social Sciences, Other Keywords: sustainability; digital transformation; suitable for aging; service ecological theory; health service
Online: 6 May 2022 (07:45:20 CEST)
The ageing transformation of digital health services faces issues of how to distinguish influencing factors, redesign services, and effectively promote measures and policies. In this study, in-depth interviews are conducted and grounded theory applied to open coding, main axis coding, and selective coding to form concepts and categories. Trajectory equifinality modeling clarified the evolution logic of digital transformation. Based on the theory of service ecology, a digital health service ageing model is constructed from the "macro-medium-micro" stages and includes governance, service, and technology transformation paths. The macro stage relies on organizational elements to promote the institutionalization of management and guide the transformation of governance for value realization, including the construction of three categories: mechanism, indemnification, and decision-making. The meso stage relies on service elements to promote service design and realize service transformation suitable for aging design, including the construction of three categories: organization, resources, and processes. The micro stage relies on technical elements to practice experiencing humanization, including the construction of three categories: target, methods, and evaluation. These results deepen the understanding of the main behaviors and roles of macro-organizational, meso-service, and micro-technical elements in digital transformation practice and have positive significance for health administrative agencies to implement action strategies.
REVIEW | doi:10.20944/preprints202111.0043.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: Skin Aging; Rejuvenation; Skin Cream; Retinoid formulation; RetileX-A; Vercilex
Online: 2 November 2021 (10:55:27 CET)
Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.
ARTICLE | doi:10.20944/preprints201811.0135.v1
Subject: Life Sciences, Biotechnology Keywords: iron oxide nanoparticles; multimodal nanoparticles; biodistribution; magnetic resonance imaging; aging; coating degradation
Online: 6 November 2018 (10:37:57 CET)
Medical imaging is an active field of research that fosters the necessity for novel multimodal imaging probes. In this line, nanoparticle-based contrast agents are of special interest, since those can host functional entities either within their interior, reducing potential toxic effects of the imaging tracers, and on their surface, providing high payloads of probes, due to their large surface-to-volume ratio. The long-term stability of the particles in solution is an aspect usually under-tackled during probe design in research laboratories, since their performance is generally tested briefly after synthesis. This may jeopardize a later translation into practical medical devices, due to stability reasons. To dig into the effects of nanoparticle aging in solution, respect to their behavior in vivo, iron oxide stealth nanoparticles were used at two stages (3 weeks vs. 9 months in solution), analyzing their biodistribution in mice. Both sets of nanoprobes showed similar sizes, zeta potentials and morphology, as observed by DLS and TEM but, fresh nanoparticles accumulated in the kidneys after systemic administration, while aged ones accumulated in liver and spleen, confirming an enormous effect of particle aging on their in vivo behavior, despite barely noticeable changes perceived on a simple inspection of their structural integrity.
ARTICLE | doi:10.20944/preprints201709.0082.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: tyrosine; dose-response; aging; working memory; plasma amino acids; catecholamines; dopamine
Online: 18 September 2017 (15:48:07 CEST)
The effects of tyrosine on plasma response and cognition in aging are unknown. We assessed the dose-dependent response to tyrosine administration in older adults in both plasma tyrosine concentrations and working memory performance. In this double blind randomized cross-over trial 17 older adults (aged 60-75 years) received a single administration of 100, 150 or 200 mg/kg body weight of tyrosine. For comparison, 17 young adults (aged 18-35 years) received a dose of 150 mg/kg body weight of tyrosine. Tyrosine plasma concentrations were determined before and 90, 120, 150, 180, 210 and 240 minutes after tyrosine intake. Working memory was assessed using the N-back task at 90 minutes after tyrosine administration. Older adults showed a dose-dependent increase in plasma tyrosine concentrations (p<.001), and the plasma response was higher than for young adults with the same dose (p<.001). Load-dependent working memory performance decreased with higher doses of tyrosine (p=.048), especially in older adults with greater dose-dependent plasma tyrosine responses (p=.035). Our results show an age-related increase in plasma tyrosine response, which was associated with a dose-dependent decline in cognitive functioning in older adults.
REVIEW | doi:10.20944/preprints202208.0229.v5
Subject: Medicine & Pharmacology, Other Keywords: Anti-aging therapy; lipofuscin; SENS; TFEB; intracellular microbe; and synthetic chemotaxis
Online: 2 November 2022 (03:41:32 CET)
Lipofuscin is indigestible garbage that accumulates in the autophagic vesicles and cytosol of post-mitotic cells with age. Drs. Brunk and Terman postulated that lipofuscin accumulation is the main or at least a major driving factor in aging. They even posited that the evolution of memory is the reason why we get lipofuscin at all, as stable synaptic connections must be maintained over time, meaning that the somas of neurons must also remain in the same locale. In other words, they cannot dilute out their garbage over time through cell division. Mechanistically, their position certainly makes sense given that rendering a large percentage of a post-mitotic cell’s lysosomes useless must almost certainly negatively affect that cell and the surrounding microenvironment. Here, I explore the possibility that the accumulation of lipofuscin to some extent underlies all other categories of age-related damage as defined by Dr. Aubrey de Grey. I do not think that lipofuscin removal will reverse/prevent all forms of aging, just the major component facing us currently. In this piece, I will review what is known about lipofuscin accumulation from evolutionary and mechanistic standpoints and discuss ways of removing it from non-dividing (or slowly-dividing) cells.
ARTICLE | doi:10.20944/preprints202207.0027.v1
Subject: Materials Science, Polymers & Plastics Keywords: glass fibers; composites; environmental aging; modeling; kinetics; water; pH; temperature; orientation; durability
Online: 4 July 2022 (03:44:24 CEST)
Glass fibers slowly dissolve and age when exposed to water molecules. Such a phenomenon also occurs when glass fibers are inside fiber-reinforced composites protected by the matrix. This en-vironmental aging results in the deterioration of the mechanical properties of the composite. In structural applications, GFRPs are continuously exposed to water environments for decades (typically design lifetime is around 25 years or even more). During their lifetime, these materials are affected by various temperatures, pH acidity levels, mechanical loads, and the synergy of these factors. The rate of the degradation process depends on the nature of glass, sizing, fiber orientation, and environmental factors such as acidity, temperature, and mechanical stress. In this work, degradation of typical industrial grade R-glass fibers, when inside an epoxy fiber-reinforced composite, is studied experimentally and computationally. A Dissolving Cylinder Zero-Order Kinetic (DCZOK) model was applied and could describe the long-term dissolution of glass composites, considering the influence of fiber orientation (hoop vs transverse), pH (1.7, 4.0, 5.7, 7.0, and 10.0), and temperature (20, 40, 60, and 80 °C). The limitations of the DCZOK model and effects of sizing protection, accumulation of degradation products inside the composite, and water availability were discussed. Experimentally dissolution was measured using ICP-MS. Like for the fibers, for GFRPs also, the temperature showed an Arrhenius-type influence on the ki-netics, increasing the rate of dissolution exponentially with increasing temperature. Similar to fibers, GFRPs showed a hyperbolic dependence on pH. The model was able to capture all of these effects, and the limitations were addressed.
ARTICLE | doi:10.20944/preprints202112.0360.v2
Subject: Engineering, Civil Engineering Keywords: earthen buildings; 3D printing; sustainability; biocomposites; aging; mechanical properties; lime carbonation; vulcanization
Online: 11 January 2022 (12:14:21 CET)
This paper is part of a study of earthen mixtures for 3D printing of buildings. To meet the ever-growing environmental needs, the focus of the paper is on a particular type of biocomposite for the stabilization of earthen mixtures—the rice husk-lime biocomposite—and on how to enhance its effect on the long-term mechanical properties of the hardened product. Having assumed that the shredding of the vegetable fiber is precisely one of the possible ways to improve the mechanical properties, we compared the results of uniaxial compression tests performed on cubic specimens made with both shredded and unaltered vegetable fiber, for three curing periods. The results showed that the hardened earthen mixture is not a brittle material in the strict sense, because it exhibits some peculiar behaviors, anomalous for a brittle material. However, being a “designable” material, its properties can be varied with a certain flexibility to get as close as possible to the desired ones. One of the peculiar properties of the hardened earthen mixture deserves further investigation, rather than corrections. This is the vulcanization that occurs (in a completely natural way) in the long term, thanks to the mineralization of the vegetable fiber by carbonation of the lime.
ARTICLE | doi:10.20944/preprints202107.0158.v1
Subject: Behavioral Sciences, Applied Psychology Keywords: Attention; Attentional Networks; Alerting; Orienting; Executive Control; Aging; Lateralization
Online: 6 July 2021 (14:52:33 CEST)
Many cognitive functions face a decline in the healthy elderly. Within the cognitive domains, both attentional processes and executive functions are impaired with aging. Attention includes three attentional networks, i.e., alerting, orienting, and executive control that showed a hemispheric lateralized pattern in adults. This lateralized pattern could have a role in modulating the efficiency of attentional networks. For these reasons could be relevant to analyze the age-related change of hemispheric specialization of attentional networks. This study aims to clarify this aspect with a lateralized version of the ANTI-Fruit. One hundred sixty-seven participants took part in this study. They are divided in three age groups: early adulthood (N=57; Range: 20-30); late adulthood (N=57; Range 31-64) and elderly/older people (N=57; Range: 65-87). Results confirm the previous outcomes on the efficiency and interactions among attentional networks. Moreover, an age-related generalized slowness was evidenced. These findings also support the hypothesis of a hemispheric asymmetry reduction in elderly/older adults. This pattern could partially explain the decrease in attentional functioning in elderly/older age.
ARTICLE | doi:10.20944/preprints202012.0115.v1
Subject: Life Sciences, Biochemistry Keywords: cognitive decline; epigenetics; HFD; aging; SAM0P8; m6A, multigenerational inheritance.
Online: 4 December 2020 (14:54:58 CET)
Environmental factors as maternal high-fat diet (HFD) intake can increase the risk of age-related cognitive decline in adult offspring. The epigenetic mechanisms are a possible link between diet effect and neurodegeneration across generations. Here, we found a significant decrease in triglyceride levels in a high-fat diet with resveratrol HFD+RV group and the offspring. Firstly, we obtained better cognitive performance in HFD+RV groups and their offspring. Molecularly, a significant increase in 5-mC levels, as well as increased gene expression of Dnmt1 and Dnmt3a in HFD+RV F1 group, were found. Furthermore, a significantly increased of m6A levels in HFD+RV F1 were found, and there were changes in gene expression of its enzymes (Mettl3 and Fto). Moreover, we found a decrease in gene expression levels of pro-inflammatory markers such as Il1-β, Il-6, Tnf-α, Cxcl-10, Mcp-1 and Tgf-β1 in HFD+RV and HFD+RV F1 groups. Moreover, there was increased gene expression of neurotrophins such as Ngf and Nt3 and its receptors TrkA and TrkB. Likewise, an increase in protein levels of BDNF and p-Akt in HFD+RV F1 was found. These results suggest that maternal RV supplementation under HFD intake prevents cognitive decline in SAMP8 adult offspring, promoting a reduction in triglycerides and leptin plasma levels, changes in the pro-inflammatory profile, restoring the epigenetic landscape as well as synaptic plasticity.
ARTICLE | doi:10.20944/preprints201904.0240.v1
Subject: Medicine & Pharmacology, General Medical Research Keywords: sarcopenia; slow gait speed; cognitive impairment; older adult; aging
Online: 22 April 2019 (11:28:59 CEST)
Cognitive impairment and sarcopenia may share common risk factors and pathophysiological pathways. This study was performed to examine the association between impairments in specific cognitive domains and sarcopenia (and its defining components) in a large group of community-dwelling older adults. Cross-sectional analysis was performed on the baseline data of 3,014 adults aged 70–84 years enrolled in the Korean Frailty and Aging Cohort Study (KFACS). The final analysis included 1,887 adults underwent dual-energy X-ray absorptiometry and cognitive function assessments. Those with disability in activities of daily living, dementia, severe cognitive impairment, Parkinson’s disease, musculoskeletal complaints, neurological disorders, or who were illiterate were excluded. Cognitive function was assessed using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet, the Frontal Assessment Battery. For sarcopenia, we used the diagnostic criteria of the Asian Working Group for Sarcopenia. The prevalence of sarcopenia was 9.6% for men and 7.6% for women. Sarcopenia (odds ratio [OR] 1.76, 95% confidence interval [CI] 1.04–2.99) and slow gait speed (OR 2.58, 95% CI 1.34–4.99) were associated with cognitive impairment in men. Only slow gait speed (OR 1.88, 95% CI 1.05–3.36) was associated with cognitive impairment in women. Sarcopenia is associated with cognitive impairment mainly due to slow gait speed. Our results suggested that cognitive impairment domains, such as processing speed and executive function, are associated with sarcopenia-related slow gait speed.
ARTICLE | doi:10.20944/preprints201810.0563.v1
Subject: Life Sciences, Biochemistry Keywords: mitochondrial metabolism; aging; monoacylglyceride; polyunsaturated fatty acids; oxidative stress
Online: 24 October 2018 (09:40:31 CEST)
During the last decade, essential polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) derived from marine sources have been investigated as nonpharmacological dietary supplements to improve different pathological conditions, as well as aging. The aim of this study was to determine the effects of dietary n-3 PUFA monoacylglycerides (MAG, both EPA and DHA) on the mitochondrial metabolism and oxidative stress of a short-lifespan model, Drosophila melanogaster, sampled at five different ages. Our results showed that diets supplemented with MAG-EPA and MAG-DHA increased median lifespan by 14.6% and decreased mitochondrial proton leak resulting in an increase of mitochondrial coupling. The flies fed on MAG-EPA also had higher electron transport system capacity and mitochondrial oxidative capacities. Moreover, both n-3 PUFAs delayed the occurrence of lipid peroxidation, but only flies fed the MAG-EPA diet showed maintenance of superoxide dismutase activity during aging. Our study therefore highlights the potential of n-3 PUFA monoacylglycerides as nutraceutical compounds to delay the onset of senescence by acting directly or indirectly on the mitochondrial metabolism, and suggests that Drosophila could be a relevant model for the study of the fundamental mechanisms linking the effects of n-3 PUFAs to aging.
ARTICLE | doi:10.20944/preprints201803.0123.v1
Subject: Engineering, Electrical & Electronic Engineering Keywords: light-emitting diodes; failure mechanisms; current-stress aging; reliability
Online: 15 March 2018 (16:32:48 CET)
We have experimentally analyzed multi-azimuth degradation mechanisms that govern failures of commercially-available high-power (1 Watt) phosphor-coated white (hppc-W) light-emitting diodes (LEDs) covered with peanut-shaped lens under three current-stress aging (CSA) conditions. Comprehensive analyses focus on photometric, chromatic, electrical, thermal, and packaging characteristics. At the packaging level, (a) the decrease of the phosphor-conversion efficiency, (b) the yellow-browning of the optical lens, and (c) the darkening of the silver-coated reflective layer deposited with extraneous chemical elements (e.g., C, O, Si, Mg, and Cu, respectively) contribute collectively to the integral degradation of the optical power. By contrast, Ohmic contacts, thermal properties, and angles of maximum intensity remain unchanged after 3840 h aging in three cases. Particularly at the chip level, the formation of point defects increases the number of non-radiative recombination centers, and thus decreases the optical power during aging stages. Nevertheless, in view of the change of the ideality factor, the dopant activation and the annealing effect facilitate the increase of the optical power in two specific aging stages (192 h∼384 h and 768 h∼1536 h), respectively. This work offers a systematic guidance for the development of reliable LED-based light sources in general-lighting areas.
ARTICLE | doi:10.20944/preprints201802.0048.v1
Subject: Biology, Anatomy & Morphology Keywords: Aging, Nutrition, Diet, Muscle atrophy, Body wasting, Food choice
Online: 5 February 2018 (23:43:16 CET)
Inadequate protein intake can impair protein balance and lead to skeletal muscle atrophy, impaired body growth, and functional decline. Foods provide both non-essential (NEAAs) and essential amino acids (EAAs) that may convey different metabolic stimuli to specific organs and tissues. In this study, we sought to evaluate the impact of six diets with various EAA/NEAA blends on body composition and the risk of developing tissue wasting in late middle-aged male mice. Mice consuming NEAA-based diets, although showing increased food and calorie intake, suffered the most severe weight loss. Interestingly, even moderate NEAAs prevalence was able to induce inflammatory catabolic stimuli, generalized body wasting and systemic metabolic alterations. Complete depletion of retroperitoneal white adipose tissue and a severe loss (>75%) of brown adipose tissue were observed together with muscle wasting. Conversely, EAA-based diets induced significant decreases in weight by reducing primarily fat reserves, but improved clinical parameters. Tissue wasting was caused by altered AA quality, independent of reduced nitrogen or caloric intake. Our results indicate that an optimized balance of AA composition is necessary for preserving overall bodily energy status. These findings are particularly relevant in the context of aging and may be exploited for contrasting its negative correlates including body wasting.
ARTICLE | doi:10.20944/preprints201810.0133.v2
Subject: Biology, Other Keywords: aging; angiotensin-converting enzyme inhibitors; nutrient metabolism; genetic background; nutritional stress
Online: 29 October 2018 (10:33:59 CET)
The angiotensin-converting enzyme (ACE) is a peptidase that is involved in the synthesis of Angiotensin II, the bioactive component of the renin-angiotensin system. A growing body of literature argues for a beneficial impact of ACE inhibitors (ACEi) on age-associated metabolic disorders, mediated by cellular changes in reactive oxygen species (ROS) that improve mitochondrial function. Yet, our understanding of the relationship between ACEi therapy and metabolic parameters is limited. Here, we used three genetically diverse strains of Drosophila melanogaster to show that Lisinopril treatment reduces thoracic ROS levels and mitochondrial respiration in young flies, and increases mitochondrial content in middle-aged flies. Using untargeted metabolomics analysis, we also showed that Lisinopril perturbs the thoracic metabolic network structure by affecting metabolic pathways involved in glycogen degradation, glycolysis, and mevalonate metabolism. The Lisinopril-induced effects on mitochondrial and metabolic parameters, however, are genotype-specific and likely reflect the drug’s impact on nutrient-dependent fitness traits. Accordingly, we found that Lisinopril negatively affects survival under nutrient starvation, an effect that can be blunted by genotype and age in a manner that partially mirrors the drug-induced changes in mitochondrial respiration. In conclusion, our results provide novel and important insights into the role of ACEi in cellular metabolism.
ARTICLE | doi:10.20944/preprints202212.0364.v1
Subject: Medicine & Pharmacology, Dermatology Keywords: Phaseolus angularis seed extract (PASE); anti-aging; health skin, cosmetic products
Online: 20 December 2022 (09:03:36 CET)
Skin photoaging is caused by prolonged exposure to ultraviolet (UV) radiation from sunlight. UV-exposed skin appears rough, thick, dry, loose, and shows deep wrinkles, and thickening. Our previous research showed that a Phaseolus angularis seed extract (PASE) effectively inhibits photoaging through UVB protection in HaCaT cells. However, its efficacy has not been evaluated in clinical trials so far. In this single-centered, randomized, double-blind study, we investigated the anti-aging effect of PASE in eye wrinkle areas. To these 21 healthy adult women aged 30 to 65, a PASE cream was applied to the right eye wrinkle area and a placebo to the left eye wrinkle area twice a day (morning and evening) for 12 weeks. The change in thick, deep crease wrinkles around the eyes was confirmed by visual evaluation, skin measurements, and a questionnaire. As a result, the R1 (surface roughness), R2 (maximum roughness), R3 (average roughness), R4 (smoothness depth), and R5 (arithmetic mean roughness) values in the group using the PASE cream all decreased. Particularly, R1, R4, and R5 significantly decreased by 18.1%, 18.6%, and 25.0%. In addition, no participants reported side effects. Our study showed that PASE led to clinically significant levels of wrinkle improvement. In conclusion, as PASE is a natural food, safe, and with few side effects, it can be a good resource for natural anti-wrinkle cosmetics in the future.
ARTICLE | doi:10.20944/preprints201908.0032.v1
Subject: Life Sciences, Molecular Biology Keywords: aging; skeletal muscle; sarcopenia; frailty; chromatin; epigenetic changes; histone modifications; Nothobranchius furzeri
Online: 2 August 2019 (12:17:03 CEST)
Aging associates with progressive loss of skeletal muscle function leading up to sarcopenia, a process characterized by impaired mobility and weakening of muscle strength. Molecular mechanisms underpinning sarcopenia are still poorly characterized. Since aging associates with profound epigenetic changes, epigenetic landscape alteration analysis in the skeletal muscle promises to highlight molecular mechanisms of age-associated sarcopenia. The study was conducted exploiting the short-lived turquoise killifish Nothobranchius furzeri (Nfu), a relatively new model for aging studies. The epigenetic analysis suggested for a less accessible and more condensed chromatin in old Nfu skeletal muscle. Specifically, an accumulation of heterochromatin regions was observed as consequence of increased levels of H3K27me3, HP1alpha, polycomb complex subunits and senescence associated heterochromatic foci (SAHFs). Consistently, euchromatin histone marks, including H3K9ac, decreased. The integrative bioinformatics analysis of RNASeq and ChIPSeq, related to skeletal muscle of Nfu at different ages, revealed a down-modulation of genes involved in cell cycle, differentiation and DNA repair and an up-regulation of inflammation and senescence genes. Undoubtedly, more studies are needed to disclose the detailed mechanisms, but this approach revealed an unprecedented specific features of Nfu skeletal muscle aging, potentially associated with sarcopenia onset and consequent impairment of swimming and mobility typical of old Nfu.
ARTICLE | doi:10.20944/preprints201704.0094.v1
Subject: Engineering, Civil Engineering Keywords: alkali silica reaction; lattice discrete particle model; concrete; creep; shrinkage; aging; deterioration
Online: 17 April 2017 (06:12:48 CEST)
Alkali Silica Reaction (ASR) is known to be a serious problem for concrete worldwide, especially in high humidity and high temperature regions. ASR is a slow process that develops over years to decades and it is influenced by changes in environmental and loading conditions of the structure. The problem becomes even more complicated if one recognizes that other phenomena like creep and shrinkage are coupled with ASR. This results in synergistic mechanisms that can not be easily understood without a comprehensive computational model. In this paper, coupling between creep, shrinkage and ASR is modeled within the Lattice Discrete Particle Model (LDPM) framework. In order to achieve this, a multi-physics formulation is used to compute the evolution of temperature, humidity, cement hydration, and ASR in both space and time, which is then used within physics-based formulations of cracking, creep and shrinkage. The overall model is calibrated and validated on the basis of experimental data available in the literature. Results show that even during free expansions (zero macroscopic stress), a significant degree of coupling exists because ASR induced expansions are relaxed by meso-scale creep driven by self-equilibriated stresses at the meso-scale. This explains and highlights the importance of considering ASR and other time dependent aging and deterioration phenomena at an appropriate length scale in coupled modeling approaches.
ARTICLE | doi:10.20944/preprints202012.0412.v1
Subject: Materials Science, Biomaterials Keywords: Hydronium jarosite; potassium jarosite; micro particles; pH; aging time; energy storage; euhedral morphology
Online: 16 December 2020 (13:41:15 CET)
Structural and morphological properties of the hydronium-potassium jarosite microstructures were investigated in this work, and their electrical properties were evaluated. All microstructures were synthesized at a reasonable temperature of 343 K with a reduced reaction time of 3 hours. Increase in the pH from 0.8 to 2.1 decreased the particle sized from 3 µm to 200 nm and increasing the aging time from 0, 3 to 7 days resulted in semispherical, spherical and euhedreal jarosite structures, respectively. A Rietveld analysis also was done, finding that increasing pH, the amount of hydronium substitution by potassium in the cationic site also increases, having a 77.72 % of hydronium jarosite (JH) plus 22.29 % potassium jarosite (JK) at pH 0.8; 82.44 % (JH) and 17.56 % (JK) at pH 1.1, and 89.98 % (JH) plus 10.02 % (JK) at pH 2.1. The results obtained in this work show that the obtained hydronium potassium jarosite microstructures with reduced particle size and euhedreal morphology can be used as anode materials for improving the life time of lithium ion batteries, due that during the analysis of the voltage obtained using electrodes made with this particles and graphite, this ranged from 0.89 to 1.36 V.
ARTICLE | doi:10.20944/preprints201909.0028.v3
Subject: Biology, Plant Sciences Keywords: Chenopodium formosanum; human dermal fibroblast; UV exposure; antioxidant activity; anti-aging; red djulis
Online: 13 November 2019 (11:02:35 CET)
Red djulis (Chenopodium formosanum) is a native cereal plant in Taiwan; it contains abundant polyphenols, betalian and dietary fiber. The appearance of red djulis is bright red. Therefore, it is also called the “ruby of cereals”. The antioxidative activity of red djulis extract is well-understood. However, the antiaging function still remains unclear. This study examined the potential of red djulis extract for enhancing collagen secretion and preventing cutaneous aging using red djulis extracts. The red djulis extracts are comprised of an abundant active component that can effectively enhance the ability of collagen secretion of dermal fibroblasts, prevent the glycation of collagen and resist the damage of ultraviolet light exposure. After fibroblast treatment with red djulis extracts, TGM1, KRT1, KRT10 and SOD2 genes were up-regulated significantly by 2.3, 4.3, 4.4 and 27.3 times, respectively, compared to those of the control group. Additionally, it can increase COL1A2 gene expression by 43% and decrease MMP9 gene expression 33%. Therefore, it was demonstrated that red djulis extracts affect gene expressions related to the skin barrier, antioxidation and collagen. Moreover, we found positive effects on skin barrier integrity, endogenous antioxidant activity and skin collagen-preservation. The preparation of the red djulis extracts is environmental friendly and can promote the economic value of Chenopodium formosanum; thus, the proposed extract is suitable for applications in the development of food products, especially beverages, skin care and cosmetic products.
ARTICLE | doi:10.20944/preprints201809.0224.v1
Subject: Medicine & Pharmacology, Other Keywords: aging; muscle; protein; metabolism; metabolomics; profiling; biomarkers; multi-marker; physical performance; multivariate
Online: 12 September 2018 (17:11:33 CEST)
Physical frailty and sarcopenia (PF&S) are hallmarks of aging that share a common pathogenic background. Perturbations in protein/amino acid metabolism may play a role in the development of PF&S. In this preliminary study, 68 community-dwellers aged 70 years and older, 38 with PF&S and 30 non-sarcopenic, non-frail controls (nonPF&S), were enrolled. A panel of 37 serum amino acids and derivatives was assayed by UPLC-MS. Partial Least Squares Discriminant Analysis (PLS-DA) was used to characterize the amino acid profile of PF&S. The optimal complexity of the PLS-DA model was found to be three latent variables. The proportion of correct classification was 76.6 ± 3.9% (75.1 ± 4.6% for enrollees with PF&S; 78.5 ± 6.0% for controls). Older adults with PF&S were characterized by higher levels of asparagine, aspartic acid, citrulline, ethanolamine, glutamic acid, sarcosine, and taurine. The profile of nonPF&S individuals was defined by higher levels of α-aminobutyric acid and methionine. Distinct profiles of circulating amino acids and derivatives characterize older individuals with PF&S. The dissection of these patterns may provide novel insights into the role played by protein/amino acid perturbations in the disabling cascade and possible new targets for interventions.
ARTICLE | doi:10.20944/preprints202002.0457.v1
Subject: Engineering, Industrial & Manufacturing Engineering Keywords: diffusion welding; diffusion bonding; cross section width; aspect ratio; material thickness; thermocouple aging
Online: 29 February 2020 (09:01:14 CET)
Diffusion bonding is often used on pre-machined parts to generate internal cavities, e.g. for cooling injection molding tools close to the mold cavity. Only then, the workpieces are finished to their final dimensions. In the case of micro-process devices, however, it is essential to precisely control the deformation, as otherwise uncontrollable pressure losses will occur with channel cross-sections in the sub-millimeter range. Post-processing is not possible. The most important process parameters for diffusion bonding are temperature, dwell time and contact pressure, with the bonding temperature and contact pressure acting in opposite directions and showing a strong non-linear dependence on deformation. In addition, the deformation is influenced by a number of other factors such as the absolute size of the cross-section and the aspect ratio of the parts, the dimensions and distribution of the internal cross sections and the overall percentage of the cross-section to be bonded. In micro process engineering, small material cross-sections in the range of the materials microstructure can facilitate additional deformation mechanisms such as grain boundary sliding, which are not relevant at all for larger structures. For parts consisting of multiple layers, tolerances in thickness and roughness of multiple surfaces must be levelled, contributing to the percentaged deformation. This makes it difficult, especially in micro process engineering and in single or small series production, to determine suitable joining parameters in advance, which on the one hand do not cause unforeseen large deformations, but on the other hand reliably produce highly vacuum-tight components. Hence, a definition of a fixed percentaged deformation does not work for all kinds of components. This makes it difficult to specify parameters for surely obtain high-vacuum tight parts. For successful diffusion bonding, atoms must diffuse over the bonding planes, forming a monolithic part in which the original layers are no longer visible. Only then, mechanical properties identical to those of the base material, which has been subjected to identical heat treatment, can be achieved. In this paper, the impacts of different material cross section widths as well as of the aspect ratio on deformation were investigated. By accident, it was found that also accuracy of the temperature measurement may have a serious impact in terms of deformation.