Cellular aging has drawn the attention of researchers, scientists, and biotech businesses for the treatment of a number of medical conditions. Cellular aging is primarily defined by consistent cessation of proliferative development in response to internal and external stressors, including DNA damage, telomere shortening, mitochondrial dysfunction, and regulation of the senescence-associated secretory phenotype (SASP). Disturbances involving these factors may contribute to age-related disease development. Therefore, the current review aims to explore anti-aging factors targeting DNA damage response and SASP regulation and their detailed signaling networks. In addition, it provides an opportunity for researchers to identify not only anti-aging targets, but also anti-aging therapeutic strategies based on identified and non-identified targets.

Cellular senescence is characterized by permanent proliferation and migration arrest, senescence-associated secretory phenotype (SASP), and oxidative stress. Senescent vascular smooth muscle cells (VSMCs) contribute to cardiovascular diseases and atherosclerotic plaque instability. To establish and characterize a model of replicative senescence (RS), human aortic VSMCs were serially passaged to represent different stages of RS such as young proliferating cells and old/senescent non-proliferating cells. More than 50% of old cells stained positive for the senescence-associated β-galactosidase compared to 20% of young cells. Old cells have a slower proliferation rate, a migratory activity reduced by 50%, but increased levels of TP53 and of cell cycle inhibitors p21/p16 expression, and accumulate in the G1 phase. Old cells showed a flattened appearance and enlarged and regular nuclei, and downregulation of the expression of LMNB1 and HMGB1. Old cells showed also an increased expression of SASP molecules (IL1β, IL6, IL8, and MMP3). Moreover, among a set of 12 manually selected long non-coding RNAs (lncRNAs), we detected significant upregulation of PURPL and NEAT1. We observed also increased levels of RRAD mRNA. The detection of novel molecular markers of senescence, such as RRAD, PURPL, and NEAT1, could be helpful for future studies on potential anti-aging factors.

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.

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.

One of the most striking findings in biogerontology in the 2010s was the demonstration that elimination of senescent cells delays many late-life diseases and extends lifespan in mice. This implied that accumulation of senescent cells promotes late-life diseases, particularly through action of senescent cell secretions (the senescence-associated secretory phenotype or SASP). But what exactly is a senescent cell? Subsequent to the initial characterization of cellular senescence it became clear that, prior to aging, this phenomenon is in fact adaptive. It supports tissue remodeling functions in a variety of contexts, including embryogenesis, parturition and acute inflammatory processes that restore normal tissue architecture and function, such as wound healing, tissue repair after infection, and amphibian limb regeneration. In these contexts such cells are normal and healthy, and not in any way senescent in the true sense of the word, as originally meant by Hayflick. Thus, it is misleading to refer to them as “senescent”. Similarly, the common assertion that senescent cells accumulate with age due to stress and DNA damage is no longer safe, particularly given their role in inflammation - a process that becomes persistent in later life. We therefore suggest that it would be useful to update some terminology, to bring it into line with contemporary understanding, and to avoid future confusion. To open a discussion of this issue, we propose replacing the term cellular senescence with remodeling activation, and SASP with RASP (remodeling-associated secretory phenotype).

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.

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.

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.

Herbal cosmetics are cosmetics derived from plants. One example is bakuchiol. Bakuchiol is a meroterpene phenol from the seeds of the Psoralea corylifolia plant. Bakuchiol can be derived from Psoralea grandulosa, Pimelea drupaceae, Ulmus davidiana, Otholobium pubescens, and Piper longum. Bakuchiol has antioxidant, anti-inflammatory, and anti-aging activities such as retinol. Bakuchiol will replace retinol with much better safety. Bakuchiol and retinoids share similar cellular pathways, such as the regulation of retinoic acid, the expression of collagen, and extracellular matrix synthesis enzymes. Bakuchiol has many benefits for the skin, so cosmetics and skin therapy can use bakuchiol. This review aims to provide information about the activity of bakuchiol, which has benefits for facial skin, so that this review can be a reference in making cosmetics containing bakuchiol. Bakuchiol has many benefits for skincare such as anti-aging, anti-hyperpigmentation, anti-oxidant, anti-inflammatory, anti-acne, and anti-melanogenesis. Products containing bakuchiol on the market are cleansers, serum, nanoemulsion, and cream.

Inotodiol, a lanostane-type triterpenoid, and many phytochemicals from Chaga mushroom have been investigated for various allergic diseases. However, antiaging and anti-inflammatory activities of inotodiol under different types of oxidative stress and impact of inotodiol on collagen and hyaluronan synthesis are not sufficiently studied. Lanostane triterpenoids-rich concentrate, which contained 10% inotodiol as major (the inotodiol concentrate), was prepared from Chaga and compared with pure inotodiol in terms of anti-inflammatory activities on a human keratinocyte cell line, HaCaT cells, under various stimulation such as stimulation with ultraviolet (UV) B or tumor necrosis factor (TNF)-α. In stimulation with TNF-α, interleukin (IL)-1β, IL-6, and IL-8 genes were significantly repressed by 0.44~4.0 μg/mL of pure inotodiol. UVB irradiation induced overexpressions of pro-inflammatory cytokines, but those genes were significantly suppressed by pure inotodiol or inotodiol concentrate. Moreover, pure inotodiol/inotodiol concentrate could also modulate synthesis of collagen and hyaluronic acid by controlling COL1A2 and HAS2/3 expression, which implies a crucial role of pure inotodiol/inotodiol concentrate in prevention of skin aging. These results enlighten anti-inflammatory and anti-aging effect of pure inotodiol/inotodiol concentrate, and it is highly conceivable that pure inotodiol and inotodiol concentrate could be promising natural bioactive substances to be incorporated in therapeutic and beautifying applications.

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.

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.

Across different cultures around the globe, human beings have historically depended largely on medicinal plants for managing diseases that have hitherto threatened their optimal health, survival, and longevity. Evidently, the health-derived benefits of medicinal plants can be strongly attributed to the presence of secondary metabolites, particularly polyphenols. The health-promoting effects of Sorghum bicolor supplement Jobelyn® (SBSJ) —a unique supplement derived from the leaf sheaths of a West African variety of Sorghum bicolor (L.) Moench—have also been ascribed to its high levels of polyphenols. This review seeks to gather and synthesize findings from various experimental and clinical studies on the health benefits of SBSJ in arthritis, cancer, chronic viral infections, stroke, anaemia, and aging. SBSJ has been reported to contain potent bioactive polyphenolic compounds with polyvalent biological activities, including antioxidant, anti-inflammatory, immunomodulatory, chemopreventive, and neuroprotective activities. Moreover, the probable benefits of SBSJ in chronic viral infections (e.g., HIV/AIDS and COVID-19) have been attributed to its potent anti-inflammatory and immunomodulatory activities. As this supplement is increasingly becoming one of the fastest-selling herbal medicines in Nigeria, there is a need for more robust studies (including clinical trials) in order to replicate and validate the prior insights gleaned from experimental studies.

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 may to some extent exacerbate every other kind of age-related damage. 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 a method of removing it from single cells in vitro.

The enhancement of human living conditions has resulted in an increase in average life expectancy, giving rise to a novel social and medical challenge: aging, which diminishes the overall quality of human life. The aging process of the body begins through the activation of effector signaling pathways of aging in cells, loss of their normal functions and deleterious effects on the microenvironment, which leads to chronic inflammation and similar transformation of neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated mortality risk. Among the most encouraging methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. The review explores the strategies and advancements in the field of anti-aging therapies that are currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches.

Nonalcoholic fatty liver disease (NAFLD) is a liver metabolism-associated steatohepatitis caused by non-alcoholic factors. NAFLD is currently the most prevalent liver disease in the world, affecting one-fourth of the world's population, and its prevalence increases with age. There are no approved drugs specifically for the treatment of NAFLD, and one important reason hindering drug development is the lack of effective biomarkers. C-reactive protein (CRP), a marker of inflammation, has been linked to NAFLD and aging in recent studies. Coincidentally, hepatocytes are responsible for the major CRP production, and the levels of CRP increase with age. Therefore, CRP is not only a potential marker, but also acts as a key factor driving liver aging and NAFLD. Herein, we reviewed the biological function and production mechanism of CRP and the relationship between CRP and NAFLD. We also comprehensively described the potential molecular mechanisms of CRP-mediated signaling in aging-associated NAFLD. Finally, we proposed possible therapeutic approaches based on the mechanism of CRP signaling in the pathogenesis of NAFLD. We hope this study can provide new insights into the development of aging associated NAFLD biomarkers and suggest that modulation of CRP signaling is a potential therapeutic target.

Multidrug resistance protein 4 (MRP4) is an energy-dependent membrane transporter that is responsible for cellular efflux of a broad range of xenobiotics and physiological substrates. In this trial, we aimed to investigate the co-effects of aging and MRP4 deficiency using gene expression microarray and morphological and electrophysiological analyses of the mouse retina. Mrp4-knockout (null) mice and wild-type (WT) mice were reared in the same condition to 8–12 wk (young) or 45–55 wk (aged). Microarray analysis identified 186 differently expressed genes from the retinas of aged Mrp4-null mice as compared to that from aged WT mice, and subsequence gene ontology and KEGG pathway analyses showed that differently expressed genes were related to lens, eye development, vision, and transcellular barrier function that are involved in metabolic pathways or viral infection pathways. No significant change in thickness was observed for each retinal layer among young/aged WT mice and young/aged Mrp4-null mice. Moreover, immunohistochemical analyses of retinal cell type did not exhibit an overt change in the cellular morphology or distribution among the 4 age/genotype groups, and the electroretinogram responses showed no significant differences in the amplitude or the latency between aged WT mice and aged Mrp4-null mice. Aging would be an insufficient stress to cause some damage to the retina in the presence of MRP4 deficiency.

Smoking is a pervasive global health concern associated with a myriad of diseases, but its impact on cellular aging, particularly in relation to telomeres, is increasingly recognized. Telomeres, protective caps at the ends of chromosomes, play a crucial role in maintaining genomic integrity. This review critically examines the existing evidence on the association between smoking and telomere atrophy, exploring the molecular mechanisms involved and the implications for accelerated aging and heightened disease risk. The comprehensive analysis encompasses both cross-sectional and longitudinal studies, elucidating potential gender and age disparities. Insights into the molecular pathways linking smoking to telomere shortening are discussed, along with the broader implications for public health. The review concludes by outlining potential interventions and suggesting future research directions in this critical area.

Prediabetes, a pivotal phase in glucose metabolism between normalcy and diabetes, exerts a profound influence on the aging process and the risk of age-related diseases. This comprehensive review delves into the intricate web of blood-based biomarkers that collectively expedite senescence, marking the transition from a state of health to age-related complications. Key findings underscore the significance of diverse biomarkers, such as telomere length, p16INK4a, senescence-associated secretory phenotype (SASP) factors, DNA methylation clocks, advanced glycation end products (AGEs), inflammatory and oxidative stress markers, circulating hormones, and additional factors like folate, B12, osteocalcin, and more. Not only do these biomarkers serve as indicators of senescence, but they actively fuel chronic inflammation, oxidative stress, and metabolic dysregulation, all of which contribute to accelerated aging. The implications of this understanding are profound, as prediabetes emerges as a critical period in an individual's life, influencing various physiological systems, including the vascular and neural systems, metabolic functions, hormonal regulation, and bone health. Recognizing the profound influence of prediabetes on senescence provides a foundation for personalized intervention strategies to mitigate age-related complications and promote healthy aging. Future research directions call for a more diverse array of biomarkers, in-depth exploration of their roles, and the development of tailored precision medicine strategies to ensure a holistic understanding and effective management of prediabetes-induced senescence and its implications for aging. This knowledge has far-reaching implications for public health and clinical practice, emphasizing the need for early detection and intervention in prediabetic individuals to enhance the quality of life in an aging population with diverse needs.

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.

The problem of increasing life expectancy is solved with the help of many medical and social areas. It has been established that piRNAs and miRNAs can significantly modify the expression of protein-coding genes by suppressing the translation process. The aim of this work was to establish the possibility of binding piRNAs and miRNAs with mRNA of the KLOTHO and FGF23 genes, which promote health and increase life expectancy through participation in key metabolic processes. We used the MirTarget program, which determines the quantitative characteristics of complementary interactions of all piRNAs and miRNAs nucleotides with mRNA of the genes. piR-44682, piR-1940042, piR-3008660, piR-3215034, piR-6885965, piR-7980636 and one miRNA (ID00756.3p-miR) binding to the mRNA of the KLOTHO gene were found in one cluster of binding sites (BSs). piRNA-6890096 interacted with the mRNA of KLOTHO gene in a fully complementary manner using only canonical nucleotides. Among 17494 human genes, target genes interacting with five piRNAs that bind to the mRNA of KLOTHO gene were identified. mRNA of the AFF2, BCL2L11, CPT1A, DAZAP1, NDRG3, SKIDA1, WBP4, ZIC5, ZSWIM6 genes interacted with piR-3215034 and piR-6885965, which formed clusters of BSs located in 5'UTR, CDS and 3'UTR. The piR-576442, piR-1501557, piR-1845735, piR-2069834, and piR-3029987 had BSs in the mRNAs of the FGF23 gene, located only in the 3'UTR. It is proposed to use piRNAs and miRNAs as regulators of the expression of KLOTHO and FGF23 anti-aging genes.

Oligonol is a low-molecular-weight polyphenol derived from lychee fruit. This study was conducted to examine whether oligonol has an ameliorative effect on diabetes-induced pancreatic damage via oxidative stress-induced inflammation. Oligonol was orally administered at 10 or 20 mg/kg body weight/day for 10 days to streptozotocin-induced diabetic rats, and changes in serum glucose, C-peptide, insulin, reactive oxygen species (ROS), and thiobarbituric acid-reactive substance (TBARS) levels as well as body weight and food and water consumption were assessed. Furthermore, rat pancreases were analyzed for weight, ROS generation, TBARS level, insulin content, and protein expressions of phosphor (p)-p38, p-extracellular-signal regulated kinase 1/2, p-inhibitor of nuclear factor kappa Bα, nuclear factor-kappa Bp65, cyclooxygenase-2, inducible nitric oxide synthase, tumor necrosis factor-α, and interleukin-6. Markers of diabetes were shown to be decreased by oligonol administration and histological damage in the pancreas was also ameliorated. These results indicate that oligonol exerts antidiabetic activities, which may be mediated via antioxidative, stress-related, anti-inflammatory signaling.

Neural electrode insertion trauma impedes the recording and stimulation capabilities of numerous diagnostic and treatment avenues. Implantation leads to the activation of inflammatory markers and cell types, which is detrimental to neural tissue health and recording capabilities. Oxidative stress and inflammation at the implant site have been shown to decrease with chronic administration of antioxidant melatonin at week 16, but its effects on the acute landscape have not been studied. To assess the effect of melatonin administration in the acute phase, specifically the first week post-implantation, we utilized histological and q-PCR methods to quantify cellular and molecular indicators of inflammation and oxidative stress as well as two-photon microscopy to track the microglial responses in real-time. Histological results indicate that melatonin effectively maintained neuron density surrounding the electrode, inhibited accumulation and activation of microglia, astrocytes, and reduced oxidative tissue damage. The expression of the pro-inflammatory cytokines, TNF-α and IL-6, were significantly reduced in melatonin-treated animals. Additionally, microglia encapsulation of the implant surface was inhibited by melatonin as compared to control animals following implantation. Our results combined with previous research suggest that melatonin is a particularly suitable drug for modulating inflammatory activity around neural electrode implants both acutely and chronically, translating to more stable and reliable interfaces.

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.

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.

Multiple sclerosis (MS) is a chronic autoimmune inflammatory disease that affects the nervous system. Peripheral blood leukocyte telomere length (LTL) and mitochondrial DNA copy number (mtDNA-CN) are potential biomarkers of disability and neurological damage. The present work evaluated LTL and mtDNA-CN in 75 relapsing-remittent MS (RRMS) patients 50 of whom had an Expanded Disability Status Scale (EDSS) 0 to 3 (mild-moderate disability), and 25 had an EDSS of 3.5 to 7 (severe disability). Absolute LTL and absolute mtDNA-CN were measured via real-time polymerase chain reaction (qPCR). The LTL and mtDNA-CN were significantly lower in RRMS severe disability than in RRMS mild-moderate disability (3.924 ± 0.124 vs 2.854 ± 0.092, p<00001; 75.14 ± 1.77 vs 68.06 ± 1.608, p<0.00001, respectively). The LTL and mtDNA-CN showed a linear correlation in RRMS with mild-moderate disability (r=0.2986, p=0.0351). In addition, in a binary logistic regression model the LTL can predict severe disability (AUC=0.697, p=0.0031, cutoff ≤ 3.0875 Kb, sensitivity= 73.1%, specificity=62.5%), the prediction is improved by including age to the model (AUC=0.765, <0.0001, sensitivity=78.26%, specificity=81.25%). Aging is closely linked to the development of disability in RRMS and can be evaluated through LTL and mtDNA-CN absolute quantification.

Epigenetic modifications, mainly aberrant DNA methylation, have been shown to silence the ex-pression of genes involved in epigenetic diseases, including cancer suppression genes. Almost all conventional cancer therapeutic agents, such as the DNA hypomethylation drug, 5-aza-2-deoxycytidine, have insurmountable side effects. To investigate the role of ectoine in skin cell DNA methylation and cancer cell proliferation, comprehensive methylome sequence analysis, 5-methyl cytosine (5mC) analysis, proliferation and tumorigenicity assays, and DNA methyla-tion-related gene and marker analysis were performed. The results showed that ectoine hypo-methylation in skin cells, especially in the CpG island (CGIs) element and 5mC, was significantly reduced. Moreover, ectoine mildly inhibited skin cell proliferation, but did not induce tumorigenicity in HaCaT cells injected into athymic nude mice. HaCaT cells treated with ectoine for 24 weeks modulated the mRNA expression levels of Dnmt1, Dnmt3a, Dnmt3b, Dnmt3i, Hdac1, Hdac2, Kdm3a, Mettl3, Mettl14, Igf2, Snrpn, and Mest. Overall, ectoine, an excellent DNA protectant, mildly de-methylates DNA in skin cells, modulates the expression of methylation-related genes, and reduces cell proliferation. This evidence suggests that ectoine is a potential anti-aging agent that prevents DNA hypermethylation and subsequently activates cancer-suppressing genes.

Functional magnetic resonance imaging (fMRI) is an indirect measure of neural activity with the hemodynamic response function (HRF) coupling it with unmeasured neural activity. The HRF, modulated by several non-neural factors, is variable across brain regions, individuals and populations. Yet, a majority of resting-state fMRI connectivity studies continue to assume a non-variable HRF. In this article, with supportive prior evidence, we argue that HRF variability cannot be ignored as it substantially confounds within-subject connectivity estimates and between-subjects connectivity group differences. We also discuss its clinical relevance with connectivity impairments confounded by HRF aberrations in several disorders. We present limited data on HRF differences between women and men, which resulted in a 15.4% median error in functional connectivity estimates in a group-level comparison. We also discuss the implications of HRF variability for fMRI studies in the spinal cord. There is a need for more dialogue within the community on the HRF confound, and we hope that our article is a catalyst in the process.

A frequent co-morbidity of cerebrovascular pathology and Alzheimer's disease pathology has been observed over past decades. Accordingly, much evidence has been reported which indicates that microvascular endothelial dysfunction, due to cerebrovascular risk factors (e.g., atherosclerosis, obesity, diabetes, smoking, hypertension, aging), precedes cognitive decline in Alzheimer's disease and contributes to its pathogenesis. By incorporating appropriate drug(s) into biomimetic (lipid cubic phase) nanocarriers, one obtains a multitasking combination therapeutic which targets certain cell-surface scavenger receptors, mainly class B type I (i.e., SR-BI), and crosses the blood-brain barrier (BBB). Such targeting allows for various Alzheimer's-related cell types to be simultaneously searched out, in vivo, for localized drug treatment. This in vivo targeting advantage may be particularly important for repurposing an FDA-approved drug, especially one which has shown the added ability to restore some cognitive functions in certain animal models of Alzheimer's disease (e.g., the anticancer drug bexarotene); this (candidate repurposing) drug up to now, by itself (i.e, without nanocarrier), displayed poor CNS penetration in human subjects.

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.

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.

Anti-DNA antibodies are hallmark autoantibodies produced in systemic lupus erythematosus (SLE), but their pathogenetic roll is not fully understood. Accumulating evidence suggests that some anti-DNA antibodies enter different types of live cells and affect the pathophysiology of SLE by stimulating or impairing these cells. Circulating neutrophils in SLE are activated by type I interferon or other stimuli and primed to release neutrophil extracellular traps (NETs) on additional stimulation. Anti-DNA antibodies are also involved in this process and may induce NET release. Thereafter, they bind and protect extracellular DNA in the NETs from digestion by nucleases, resulting in increased NET immunogenicity. This review discusses the pathogenetic role of anti-DNA antibodies in SLE, mainly focusing on recent progress in the two research fields concerning antibody penetration into live cells and NETosis.

Background: Sulforaphane (SFN) is an isothiocyanate of vegetables origin with potent antioxidant and immunomodulatory properties. The pleiotropic activities characterization in human dendritic cells (DCs) is poorly summarized. The aim of this work was the study of the immunomodulatory power of SFN in response to an inflammatory microenvironment on human monocyte derived DCs (moDCs). Methods: The immunological response induced by SFN was studied, evaluating apoptosis and autophagy assays by flow cytometry in moDCs and cancer cell line (THP-1), including moDCs maturation, lymphocyte proliferation and cytokines production under different experimental conditions associated or not with an inflammatory microenvironment, which was induced by lipopolysaccharide (LPS). Results: Our results demonstrated that SFN can interact with moDCs, significantly reducing autophagy process and enhancing apoptosis, such as THP-1 cells, in chronic inflammatory microenvironment. Under this chronic inflammation, SFN modulated the phenotypical characteristics of moDCs, which reduction the expression of all markers (CD80, CD83, CD86, HLA-DR and PD-L1), and significantly reduced the Th2 proliferative response together with the reduction of the IL-9 and IL-13 levels. Although we did not find changes in the regulatory proliferative response, we observed an increase in IL-10 levels. Conclusion: These findings demonstrate that SFN exerts protective effects against LPS-induced inflammation through moDCs/T-cells modulation towards a regulatory profile. Therefore, SFN may be a potential candidate for use in the treatment of pathologies with an inflammatory profile.

Caseinolytic peptidase P (CLPP) plays a central role in mitochondrial unfolded protein response (mtUPR) by promoting the breakdown of misfolded proteins and setting in motion a cascade of reactions to re-establish protein homeostasis. Global germline deletion of Clpp in mice results in female infertility and accelerated follicular depletion. Telomeres, on the other hand, are tandem repeats of 5’-TTAGGG-3’ sequences found at the ends of the chromosomes. Telomeres are essential for maintaining chromosome stability during somatic cell division and their shortening is associated with cellular senescence and aging. In this study, we asked whether the infertility and ovarian aging phenotype caused by global germline deletion of Clpp is associated with somatic aging, and tested telomere length in tissues of young and aging mice. We found that impaired mtUPR caused by the lack of CLPP is associated with accelerated telomere shortening in both oocytes and somatic cells of aging mice. In addition, expression of several genes that maintain telomere integrity were decreased, and double strand DNA breaks were increased in telomeric regions. Our results highlight how impaired mtUPR can affect telomere integrity and demonstrate a link between loss of mitochondrial protein hemostasis, infertility, and somatic aging.

We previously showed that mice with knockout in the peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PPARGC1A) gene encoding the PGC-1a protein and nuclear factor erythroid 2 like 2 (NFE2L2) gene, showed some features of the age-related macular degeneration (AMD) phenotype. To further explore the mechanism behind the involvement of PGC-1a in AMD pathogenesis we used young (3-month) and old (12-month) mice with knockout in the PPARGC1A gene and age-matched wild-type (WT) animals. An immunohistochemical analysis showed age-dependent different expression of markers of oxidative stress defense, senescence and autophagy in the retinal pigment epithelium of KO animals as compared with their WT counterparts. Multivariate inference testing showed that senescence and autophagy proteins had the greatest impact on the discrimination between KO and WT 3-month animals, but proteins of antioxidant defense also contributed to that discrimination. A bioinformatic analysis showed that PGC-1a might coordinate the interplay between genes encoding proteins involved in antioxidant defense, senescence and autophagy in the aging retina. These data support importance of PGC-1a in AMD pathogenesis and confirm the utility of mice with PGC-1a knockout as an animal model to study AMD pathogenesis.

This prospective study provides data on long-term humoral immunogenicity of a heterologous off-label vaccine regimen combining the adenoviral vectored ChAdOx1 nCoV-19 from Astra-Zeneca (ChAd) with the mRNA-1273 vaccine from Moderna (m1273) in comparison to two different homologous mRNA vaccine schedules. Of the 316 COVID-19 naïve adult health care workers (HCW) included to complete a survey on vaccine-associated symptoms (VAS), 197 had received the homologous BNT162b2 mRNA vaccine from Pfizer/BioNTech (BNT/BNT), 76 the homologous m1273/m1273, and 43 the heterologous ChAd/m1273 vaccine regimen. Concentration of antibodies against SARS-CoV-2 spike protein in plasma 5-7 months after the second vaccine dose was higher in the m1273/m1273 and ChAd/m1273 than the BNT/BNT vaccine group. The frequency of systemic VAS after first vaccine dose was 86% after ChAd compared to 35% and 39% after BNT and m1273, respectively (p &lt; 0.0001), and after second vaccine dose highest (89%) in the m1273/m1273 group (p &lt; 0.001). Individuals with systemic VAS achieved higher levels of antibodies irrespective of vaccine regimen. In conclusion, VAS serve as a strong predictor of long-term humoral immune response, and the heterologous ChAd/m1273 vaccine regimen provides an at least equal long-term humoral immune response compared with the standard vaccine regimens used in Denmark.

A new biodegradable paper-based film is a hot research topic in the development of green agriculture. In this paper, a black paper base film coated with cooked tung oil with excellent mechanical properties, hydrophobic surface, high heat transfer and strong weather resistance was prepared by spraying high pigment carbon black solution on the surface of base paper. The results showed that the surface solidified oil film with rough structure was made by the brush coating process of cooked tung oil, and the base film of black paper was given hydrophobic structure, and the contact angle reached 98.9 °. Cooked tung oil permeates into the inside of the paper base, and after curing, it forms a multi-dimensional network film structure. The maximum tensile stress of the black paper base film is about 123% higher than that of the original paper base film. The coloring of carbon black makes the black paper base film have heat conduction effect, and the average heat transfer rate reaches 15.12 °C/s. Cooked tung oil is combined with the paper-based fiber high-toughness layer to form a stable system. The existence of the cured film improves the basic mechanics and hydrophobicity, and the resistance to ultraviolet radiation and hot air is greatly improved. This study provides a feasible scheme for the application of a black paper base film coated with cooked tung oil.

Mental stress represents a pivotal factor in cardiovascular diseases. The mechanism by which stress produces its deleterious effects is still under study but one of the most explored pathway is cell senescence. In this scenario, circulating microRNAs appear to be mobile regulatory elements of the telomerase activity and alternative splicing within the ”senectome” network. Anti-stress techniques seem to be able to slow-down aging process. As we have recently verified how the practice of Relaxation Response (RR), counteracting psychological stress, determines favorable changes of some inflammatory genes expression, of some neurotransmitters, hormones, cytokines and inflammatory circulating microRNAs, we aimed to verify a possible change even in serum levels of 4 senectome micro-RNAs (SE-miRNAs -20, -30, -410, -515), testing the activity of telomerase in peripheral blood mononuclear cells-PBMCs. We analyzed also alternative splicing microRNAs 134 and 183. According to our data, miRNA-20 and -30 levels and PBMCs-telomerase activity increase during the RR while -410 and -515 levels decrease. Moreover, during the RR sessions both miRNA-134 and -183 decrease. The mediators considered in this work seem to vary rapidly according to a (stress)-relaxation condition showing that psychic activity should be part of the study of aging factors.

Lifestyle health has been recognized as an evidence-based innovation that defines how daily habits and practices impact both the prevention and treatment of disease and provides an important adjunctive component to overall health. Specifically, an approach with small changes over time can have a dramatic impact on the health and well-being of individuals not only, in general, but also can be applied to skin health. However, lifestyle health factors to improve skin well-being have not been discussed extensively and/or well promulgated. The narrative for this overview focuses on providing a summary for topic background information, but more importantly, presents four lifestyle factors that can improve dermal health [i.e., factor 1: nutrition - diet; factor 2: rest (sleep); factor 3: movement/physical exercise, and factor 4: social and community associations]. This was accomplished by identifying previous journal articles and reviews with emphasis over the last five years (from January 2018 through July 2023; 156 out of 190 references cited or 82 %) using scientific search databases. The main conclusions of this overview encourage the concept that lifestyle health factors such as nutrition/diet, rest/sleep, movement/physical exercise, and community/social interactions support enhanced skin health and well-being with aging. Plus, social media interventions that aim to promote dietary, sleep and physical activity changes might be an application to improve skin health in the future.

Rice bran arabinoxylan compound (RBAC) is derived from rice bran enzymatically treated with Lentinus Edodes mycelium. This review explores biologically active compounds and mechanisms of action that support RBAC as an immunomodulating nutraceutical in generally healthy and/or aging individuals. Thirty-seven (n=37) primary research articles fulfiled the selection criteria for review. Most research is based on Biobran MGN-3, which consists of complex heteropolysaccharides with arabinoxylan as its primary structure while also containing galactan and glucan. RBAC was found to invoke immunological activities through direct absorption via the digestive tract and interaction with immune cells at the Peyer’s patches. RBAC was shown to promote the innate defence by upregulating the macrophage phagocytosis and enhancing natural killer cell activity while lowering oxidative stress. Through induction of dendritic cell maturation, RBAC also augments adaptive immunity by promoting T and B lymphocyte proliferation. RBAC acts as an immunomodulator by inhibiting mast cell degranulation during allergic reactions, attenuating inflammation, and downregulating angiogenesis by modulating cytokines and growth factors. RBAC is shown to be a safe and effective neutraceutical for improving immune health, notably in aging individuals with reduced immune function. Human clinical trials with geriatric participants have demonstrated RBAC to have prophylactic benefits against viral infection and may improve their quality of life. Further research should explore RBAC’s bioavailability, pharmacodynamics, and pharmacokinetics of the complex heteropolysaccharides within. Translational research to assess RBAC as an nuetraceutical for the aging population is still required, particularly in human studies with larger sample sizes and cohort studies with long follow-up periods.

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.

Silybum marianum (L.) Gaertn. (aka milk thistle) constitute the almost exclusive source of silymarin, a mixture of different flavonolignans, and is thus considered as a unique model for their extraction. The present research deals with ultrasound-assisted extraction (UAE) of S. marianum flavonolignans and their quantification using LC system. The optimal conditions for UAE were: aqueous EtOH 54.5% (v/v) as solvent, applying an ultrasound frequency of 36.6 kHz during an extraction time of 60 min at 45°C with a liquid to solid ratio of 25:1 ml/g DW. Following optimization, the extraction method was validated according to international standards of the association of analytical communities (AOAC) in order to ensure its precision and accuracy for the quantitation of the individual silymarin components. The efficiency of UAE was compared with maceration protocol of the same duration. The optimized and validated conditions allowed highest extraction yields of flavonolignans in comparison to maceration. The antioxidant capacity of the extracts was confirmed by the CUPRAC assays and inhibition of advanced glycation end products. The skin anti-aging action was also confirmed toward the strong in vitro inhibition capacity of the obtained extract against collagenase and elastase enzymes. The procedure presented here allows a green efficient extraction and quantification of the main flavonolignans from the fruits of S. marianum with attractive antioxidant and anti-aging activities for future cosmetic applications.

We aim to examine how happiness modifies and mediates the impact of physical activity and nu-trition on cognitive function among 699 seniors aged 60 and above in Shanghai, China. Linear regression models were used to validate the effects of nutrition and exercise on cognitive function, and to test their interaction effects with happiness. When the interactions were significant, strati-fied analyses in sub-groups were conducted. Mediation effects of happiness were examined using two-step causal mediation models. We confirmed that better nutrition (p < 0.001) and exercise (p = 0.009) were significantly associated with less cognitive decline. Furthermore, the effects of nu-trition and exercise on cognitive decline were significant in the unhappy (happiness < 20) (p <0.001) and younger (age < 74) sub-groups (p = 0.015). Happiness partially mediated 11.5% of the negative association of cognitive decline with nutrition (p = 0.015) and 23.0% of that with exercise (p = 0.017). This study suggests that happiness moderates and also partially mediates the effects of exercise and nutrition on cognitive status. The beneficial effects of exercise and nutrition were stronger in less happy or younger seniors. Future intervention studies are required to confirm this path relationship.

Background: This study aimed to assess the relationship between age-related changes in Neuro-filament Light Chain (NFL), a marker of neuronal function, and various factors including muscle function, body composition, and metabolomic markers. Methods: The study included 40 partici-pants, aged 20 to 85 years. NFL levels were measured, and muscle function, body composition, and metabolomic markers were assessed. Results: NFL levels increased significantly with age, particularly in men. Negative correlations were found between NFL levels and measures of mus-cle function, such as grip strength, walking speed, and chair test performance, indicating a decline in muscle performance with increasing NFL. These associations were more pronounced in men. NFL levels also negatively correlated with muscle quality in men, as measured by 50 kHz phase angle. In terms of body composition, NFL was positively correlated with markers of fat mass and negatively correlated with markers of muscle mass, predominantly in men. Metabolomic analy-sis revealed significant associations between NFL levels and specific metabolites, with gen-der-dependent relationships observed. Conclusions: This study provides insights into the rela-tionship between circulating serum NFL, muscle function, and aging. The findings highlight gen-der differences and contribute to our understanding of age-related changes in neuronal function and their impact on muscle health.

Information encryption and anti-counterfeiting play an important role in many aspects of daily life, such as in minimizing economic losses, protecting secure communication and public security, and so on. Owing to the high information capacity and ease of operation, luminescent materials for advanced information encryption and anti-counterfeiting are essential to meet the increasing demand on encryption security. Herein, we summarize two emerging luminescent materials for information encryption and anti-counterfeiting, the AIE materials and room-temperature phosphorescent materials. At last, we discuss the opportunities and anticipations of these two information encryption and anti-counterfeiting materials.

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.

The average age of in-service bridges has increased in recent years in the United States. To address this issue, structural health monitoring and damage identification approaches can be employed to prioritize maintenance/replacement of aging bridges. Among the damage identification and operational health monitoring approaches, finite element (FE) model updating methods can offer a solution to evaluate the mechanics-based characteristics of bridges. However, in a real-world setting, unidentifiability and mutual dependency between model parameters, modeling errors, especially due to boundary conditions, as well as ill-conditioning of updating algorithms can pose challenges to the application of FE model updating methods. To address these challenges, this study presents a two-step FE model updating approach. In the first step, modal-based model updating is used to estimate linear model parameters mainly related to the stiffness of boundary conditions and material properties. In the second step, in order to refine parameter estimation accounting for nonlinear response behavior of the bridge, a time-domain model updating is carried out. In this step, boundary conditions are fixed at their final estimates using modal-based model updating. To prevent the convergence of updating algorithm to local solutions, the initial estimates for nonlinear material properties are selected based on their corresponding final estimates in the modal-based model updating. To validate the applicability of the two-step FE model updating approach, a series of forced-vibration experiments are designed and carried out on a pair of decommissioned and deteriorated prestressed bridge I-girders. After carrying out the two-step FE model updating, the final estimates of concrete compressive strength are shown to provide reasonable assessment of the damage extent in the girders.

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.

： Anti-MDA5 antibody bearing (anti-MDA5+)-dermatomyositis (DM) or polymyositis (PM) is notorious for causing rapidly progressive interstitial lung disease (RPILD) &amp;/or cancers with high mortality rate. However, anti-MDA5 antibodies (Abs) are also found in other connective tissue diseases and their link with RPILD especially with regards to the mortality rate are unknown. We retrospectively recruited 71 patients bearing anti-MDA5-Abs in serum, stratified them in terms of a presence or absence of RPILD, and evaluated their clinical features, laboratory findings, associated myositis antibodies, concurrent connective tissue disease (CTD) as well as newly developed malignancies. Thirty-nine (55%) patients presented with DM/PM but 32 (45%) didn’t. Twenty-two of the former and 11 of the latter developed RPILD eventually, accounting for a total of 46% of all MDA5 bearing patients. On the other hand, 15 of all 71 (21.1%) patients had cancers. Among 32 patients who didn’t have DM/PM, 27 (38.0% of all 71) had other CTDs, indicating that only 5 (7.0% of 71) patients did not have CTDs. Senility (odds ratio [OR]=1.816, P=0.032), presence of anti-Ro-52 antibody (OR=1.676, P=0.018), elevated C-reactive protein (CRP, OR= 4.354, P&lt;0.001) and carcinoembryonic antigen (CEA, OR=2.625, P=0.005) posed risks for RPILD. High lactose dehydrogenase (LDH, p=0.009), CRP (p=0.001), CEA (p=0.001), ferritin (p ≤ 0.001) and low albumin (p ≤ 0.001) were significantly associated with mortality. Anti-SAE antibodies were negatively correlated with RPILD as analyzed by univariate (OR=0.245, P=0.017) and multivariate (OR= 0.058, P=0.036) regressions, indicating that they may be a protective factor from RPILD (OR= 0.543, P=0.008) or fatality (OR= 0.707, P=0.012), which was also demonstrated in subgroup analyses. In contrast to various risk factors for RPILD or mortality, anti-SAE antibodies might be conversely a protective factor in anti-MDA5+ patients.

Evolutionary medicine argues that disease can arise because modern conditions do not match those in which we evolved. For example, a decline in exposure to commensal microbes and gastrointestinal helminths in developed countries has been linked to increased prevalence of allergic and autoimmune inflammatory disorders (the hygiene hypothesis). Accordingly, microbial and helminthic probiotic therapies have been explored as Darwinian treatments for these disorders. A further possibility is that loss of old friend commensals also increases the sterile, aging-associated inflammation known as inflammaging, that contributes to a range of age-related diseases, including cardiovascular disease, dementia and cancer. Interestingly, Crowe et al. (2020) recently reported that treatment with a secreted glycoprotein from a parasitic nematode can protect against murine aging by induction of anti-inflammatory mechanisms. Here, we explore the hypothesis that restorative helminth therapy would have anti-inflammaging effects. Could worm infections provide broad-spectrum protection against age-related disease?

Advanced paternal age at fertilization has been suggested to be a risk factor for neurodevelopmental, psychiatric and other disorders in offspring. One emerging hypothesis suggests that altered offspring phenotype is linked with age-related accumulation of epigenetic changes in the sperm of fathers. Given that paternal age is increasing in the developed world, understanding aging-related epigenetic changes in sperm is needed as well as environmental factors that modify such changes. In this study, we characterize age-dependent changes in sperm DNA methylation profiles between young pubertal (postnatal day (PNDs) 65) and mature (PND120) Wistar rats. We also analyze these changes in rats exposed perinatally to 0.2 mg/kg of ubiquitous environmental xenobiotic 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47). Reduced representation bisulfite sequencing (RRBS) libraries were prepared from caudal epididymal sperm DNA and differentially methylated regions (DMRs; ≥ 10x coverage depth, ≥ 3 CpGs per cluster, ≥ 5% methylation change, q < 0.05) were identified via MethPipe package. In control animals, 5,319 age-dependent DMRs were identified, with 99.3% DMRs hypermethylated in mature animals compared to young pubertal rats. These age-related DMRs were enriched for functional categories essential for embryonic development, such as pattern specification, forebrain and sensory organ development, Hippo and Wnt pathways. Age-related changes in sncRNA, reported in different study, target similar list of genes and biological categories.In BDE-47 exposed rats, sperm DNA methylation was higher in young pubertal and lower in mature animals when compared to controls, which resulted in a significant attenuation in the number of age-dependent DMRs (N = 189) identified in the exposed group. In conclusion, our results indicate that the natural aging process has profound effects on sperm methylation levels and this effect may be modified by environmental exposures. Moreover, our results further support the role of epigenetic mechanisms as a likely link betwen paternal age and offspring health and development.

The process of preparing anti-glare thin films by spray-coating silica sol-gel to soda-lime glass was exclusively and statistically studied in this paper. The effects of sol-gel deliver pressure, air transport pressure, and spray gun displacement speed on the gloss, haze, arithmetic mean surface roughness, and total transmittance light were analyzed. The experimental results indicate that the factors of sol-gel deliver pressure, air transport pressure, and displacement speed exhibit significant effect on the haze, gloss, and Ra. In contrast, the variation of total transmittance light with these three factors are insignificant. Because the anti-glare property is predominantly determined by low gloss and high haze, therefore, we aim to minimize gloss and maximize haze to achieve high anti-glare. Central composite design and response rurface methodology are employed to analyze the main and interaction effects of the three factors through quadratic polynomial equations, which are confirmed by the analysis of variance and R². The response surface methodology predict the lowest gloss and highest haze are 9.2 GU and 57.0%, corresponding to the sol-gel deliver pressure, air-transport pressure, and displacement speed of 250 kPa, 560 kPa, and 140 mm/s, and 340 kPa, 620 kPa, and 20 mm/s, respectively. Comparing the predicted optimal data with the real experimental results validates the applicability of the mathematical model. This study provides an important basis for the subsequent production of anti-glare glass with different specifications to satisfy the market demand.

Immune checkpoint inhibitors (ICI) are currently use in a wide range of tumors, but only 20-40% of patients achieve clinical benefit. Aim of our study was to find predictive biomarkers of ICI treatment. We analyzed by immunohistochemistry various cell subsets, including CD3+ cells, CD8+ cells, CD68+ cells, CD20+ cells, FoxP3+ cells, and molecules as LAG-3, IDO1, TGfβ. Comprehensive genomic profiles were analyzed. Correlation of various biomarkers with efficacy of ICI treatment in patients with advanced solid tumors was evaluated. We evaluated 56 patients treated with ICI monotherapy. Longer median progression-free survival (PFS) was found in tumors negative for nuclear FoxP3 (P = 0.002, HR 0.14) and in TMB-high tumors (P = 0.024, HR 0.38). Longer overall survival (OS) was found in patient with intraepithelial CD8 negativity (P = 0.045, HR 0.47). In malignant melanoma CD68 negativity, FoxP3 negativity and PDL TPS ≥ 1 was associated with longer PFS. In NSCLC FoxP3 was associated with longer PFS and OS. We found that absence of expression of several biomarkers such as CD68 and FoxP3 is associated with better survival. TMB-high and PD-L1 expression not universally but in certain disease could predict response.

The APOE locus has garnered significant clinical interest because of its association with Alzheimer's disease (AD) and longevity. This genetic association appears across multiple genes in the APOE locus. Despite the apparent differences between AD and longevity, both conditions share a commonality of aging-related changes in mitochondrial function. This commonality is likely due to accumulative biological effects, partly exerted by the APOE locus. In this study, we investigated changes in mitochondrial structure/function-related markers using oxidative stress-induced human cellular models and postmortem brains (PMBs) from individuals with AD and normal controls. Our results reveal a range of expressional alterations, either up- or down-regulated, in these genes in response to oxidative stress. In contrast, we consistently observed an upregulation of multiple APOE locus genes in all cellular models and AD PMBs. Additionally, the effects of AD status on mitochondrial DNA copy number (mtDNA CN) varied depending on APOE genotype. Our findings imply a potential coregulation of APOE locus genes, possibly occurring within the same topologically associating domain (TAD) of the 3D chromosome conformation. The coordinated expression of APOE locus genes could impact mitochondrial function, contributing to the development of AD or longevity. Our study underscores the significant role of the APOE locus in modulating mitochondrial function and provides valuable insights into the underlying mechanisms of AD and aging, emphasizing the importance of this locus in clinical research.

Objectives: To determine the prevalence of controlled systemic hypertension and its associated risk factors among the hypertensive patients who attended the clinic at Mbeya Zonal Referral Hospital in Tanzania. Methods: A descriptive cross-sectional quantitative study was used determine the prevalence of co to 252 hypertensive patients were recruited during clinic visit from September to November 2020 and participant was randomly selected interviews using structured self-administered questionnaires. Data was analyzed using chi square test to find the risk factors associated with controlled hypertension. Results: Among 252 participants, 94(39.7%) individuals with controlled hypertension giving the prevalence of controlled hypertension. The proportion of females with controlled hypertension was slightly higher than male (49 females to 45 males). The prevalence of uncontrolled hypertension was 152(60.3%) participants. The prevalence of controlled hypertension was higher among patients who have regular clinic visit (p< .05) and have daily adherence to their anti-hypertensive medication. A similar trend was observed among participants without financial challenges to attend clinic, short duration of illness, higher level of education and there was no association between age, sex, marital status, smoking, alcohol consumption, having health insurance and having chronic illness. Conclusion: Prevalence of controlled hypertension is higher among patients who have regular clinic visit and have daily adherence to their anti-hypertensive medication. Also, it is higher among participants without financial challenges to attend clinic so they can have regular clinic visit and checkup. Reinforcement on regular drug intake and clinic visit, good nutrition and reduced salt intake and modifying lifestyles of patient with hypertension is important.

Fermented foods and ingredients, including fermentates derived from lactic acid bacteria (LAB) in dairy products, can modulate the immune system. Here we describe the use of reconstituted skimmed milk powder to generate novel fermentates from Lactobacillus helveticus strains SC232, SC234, SC212, and SC210, and from Lacticaseibacillus casei strains SC209 and SC229, and demonstrate using in vitro assays that these fermentates can differentially modulate cytokine secretion by bone marrow derived dendritic cells (BMDCs) when activated with either the viral ligand, loxoribine, or an inflammatory stimulus, lipopolysaccharide. Specifically, we demonstrate that SC232 and SC234 increase cytokines IL-6, TNF-α, IL-12p40, IL-23, IL-27 and IL-10, and decreased IL-1β in primary bone marrow derived dendritic cell (BMDCs) stimulated with a viral ligand. In contrast exposure of these cells to SC212 and SC210 resulted in increased IL-10, IL-1β, IL-23, and decreased IL-12p40 following activation of the cells with the inflammatory stimulus LPS. Interestingly SC209 and SC229 had little or no effect on cytokine secretion by BMDCs. Overall, our data demonstrates that these novel fermentates have specific effects and can differentially enhance key immune mechanisms that are critical to viral immune responses, or can suppress responses involved in chronic inflammatory conditions, such as Ulcerative Colitis (UC), and Crohn’s disease (CD).

According to our previous investigation the total methanol extract from Graptopetalum paraguayense E. Walther demonstrates a significant inhibitory effect on HSV-1. To clarify what causes this inhibitory activity on HSV-1, a metabolic profile of the plant was performed. Three main fractions: non-polar substances, polar metabolites and phenolic compounds were obtained and GC-MS analysis was carried out. Since it is well known that phenolic compounds show a significant anti-herpes effect and that viral DNA polymerase (DNApol) appears to play a key role in HSV virus replication, we present a docking and quantum-chemical analysis of the binding of these compounds to viral DNApol amino acids. Fourteen different phenolic acids found by GS/MS analyses, were used in molecular docking simulations. According to the interaction energies of all fourteen ligands in the DNApol pockets based on docking results, DFT calculations were performed on the five optimally interacting with the receptor acids. It was found that hydroxybenzoic acids from phenolic fraction of Graptopetalum paraguayense E. Walther show a good binding affinity to the amino acids from the active site of the HSV DNApol, but significantly lower than that of acyclovir. The mode of action on virus replication of acyclovir (by DNApol) is different from that of the plant phenolic acids one, probably.

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

With the rapid development of tumor immunotherapy, nanoparticle vaccines have attracted much attention as a potential therapeutic strategy. The potential role of the mannose-modified lipid calcium phosphate nanoparticle vaccine in enhancing the anti-tumor immune response was investigated. The aim of this study was to investigate the effect of mannose modification on the immune response of nanoparticles in regulating the tumor microenvironment through systematic review and analysis and to explore its potential clinical application in tumor therapy. Currently, despite the potential advantages of nanoparticle vaccines in immunotherapy, achieving an effective immune response in the tumor microenvironment remains a challenge. Tumor immune escape and overexpression of immunosuppressive factors limit its clinical application. Therefore, this study will explore how to intervene in the immunosuppressive mechanism in the tumor microenvironment through mannose-modified lipid calcium phosphate nanoparticle vaccines so as to improve the immunotherapy effect of tumor patients and provide new ideas and strategies for the field of tumor therapy.

Background: Vaccination is one of the most effective life-saving medical interventions, and the introduction of SARS-CoV-2 vaccines was intended to prevent the serious implications of COVID-19. The objectives of the study were: i) to observe the humoral immune response to BNT162b2 vaccine and SARS-CoV-2 infection (mainly breakthrough infections), ii) to demonstrate the persistence of anti-SARS-CoV-2 antibodies over time in relation to the number of received vaccine doses and the course of infection, and iii) to determine adverse effects after primary vaccine doses. Methods: To assess the humoral response, IgG and IgA anti-S1 antibodies were quantified by ELISA assays. In total, the tests were carried out seven times in almost two years. Results: We demonstrated strong immunogenicity (compared to levels before primary vaccination, 150- and 20-fold increases in IgG and IgA, respectively) of the BNT162b2 vaccine. Over time, we observed a systematic decline in antibody levels, which may have contributed to breakthrough infections. Although they caused seroconversion similar to the booster, antibody levels in such patients fell more rapidly than after re-vaccination. On the other hand, in individuals who did not receive booster(s) and who did not present breakthrough infection, anti-SARS-CoV-2 antibodies returned to pre-vaccination levels after 20 months. The most commonly recognized adverse effects were injection site redness and swelling. Conclusion: Vaccination is highly effective in preventing the most severe outcomes of COVID-19 and should be performed regardless of prior infection. Booster doses significantly enhance anti-SARS-CoV-2 antibody levels and, in contrast to those obtained by breakthrough infection, they remain longer.

The BNT162b2 vaccine is globally used for preventing morbidity and mortality related to COVID-19. Cancer patients have had priority for receiving the vaccine due to their diminished immunity. This study reports the response of administering the 3rd and 4th vaccine doses to can-cer patients receiving active anti-neoplastic treatment. 142 patients have received two doses of the mRNA-based BNT162b2 COVID-19 vaccine, while 76 and 25 patients have received three and four doses, respectively. The efficacy of the humoral response following two vaccine doses was diminished in cancer patients, especially in the group of patients receiving chemotherapy. In a multivariate analysis, patients after three and four BNT162b2 vaccine doses were more likely to have antibody titers in the upper tertile compared to patients after two doses of the vaccine (odds ratio (OR) 7.62 (95% CI 1.38-42.12), p=0.02 and 17.15 (95% CI 5.01-58.7), p<0.01, respective-ly). Unlike the response after two doses, the 3rd and 4th BNT162b2 vaccine booster doses, had an increased efficacy of 95-100% in cancer patients while on active treatment. This result could be explained by different mechanisms including the development of memory B cells.

(1) Background: TNF inhibitors (TNFi) have revolutionized the treatment of rheumatoid arthritis (RA). However, 30-40 % of RA patients do not respond adequately to those biologics. In addition to neutralizing soluble TNF, TNFi have the ability to bind the transmembrane form of TNF, tmTNF. Importantly, tmTNF can act itself as a receptor that induces a “Reverse Signaling” (RS) in cells. We previously showed that certolizumab, a Fab’ TNFi, activates RS in human primary monocytes, at least in part through the transcription factor NRF2 that is known to regulate the expression of genes involved in anti-inflammatory response and oxidative stress. (2) Methods: Here, we have developed an assay for the prediction of clinical response of RA patients to TNF inhibitors. This assay is based on mRNA quantitation of CD36 activation and of 6 genes induced by NRF2 following tmTNF RS in fresh monocytes. (3) Results: We could predict the response to anti-TNF monoclonal antibodies (mAbs) with 93.3 % accuracy. However, our method was not suitable for the prediction of the response to TNF soluble receptor etanercept. (4) Conclusions: We have developed a rather simple, short-term, test that can be standardized. Predicting the response to TNF mAbs will help physicians offer the best available treatment and provide patients with personalized medicine.

Background & aims It is documented that low protein and amino-acid dietary intake is related to poorer cognitive health and increased risk of dementia. Degradation of the neuromodulatory pathways, (comprising the cholinergic, dopaminergic, serotoninergic and noradrenergic systems) is observed in neurodegenerative diseases and impairs the proper biosynthesis of key neuromodulators from micro-nutrients and amino acids. How these micro-nutrients are linked to neuromodulatory pathways in healthy adults is less studied. The Locus Coeruleus–Noradrenergic System (LC-NA) is the earliest subcortical structure affected in Alzheimer’s disease, showing marked neurodegeneration, but is also sensitive for age-related changes. The LC-NA system is critical for supporting attention and cognitive control, functions that are enhanced both by tyrosine administration and chronic tyrosine intake. The purpose of this study was to 1) investigate whether the dietary intake of tyrosine, the key precursor for noradrenaline (NA), is related to LC integrity 2) whether LC integrity mediates the reported association between tyrosine intake and higher cognitive performance (measured with Trail Making Test – TMT), and 3) whether LC integrity relates to an objective measure of brain maintenance (BrainPAD). Methods The analyses included 398 3T MRIs of healthy participants from the Berlin Aging Study II to investigate the relationship between LC integrity and habitual dietary tyrosine intake-daily average (HD-Tyr-IDA). As a control procedure, the same analyses were repeated on other main seeds of the neuromdulatory subcortical system (Dorsal and Medial Raphe, Ventral Tegmental Area and Nucleus Basalis of Meynert). In the same way, the relationships between the five nuclei and BrainPAD were tested. Results Results show that HD-Tyr-IDA is positively associated with LC integrity. Similarly, LC integrity disproportionally relates to better brain maintenance (BrainPAD). Mediation analyses reveal that only LC, relative to the other nuclei tested, mediates the relationship between HD-Tyr-IDA I and performance in the TMT and between HD-Tyr-IDA and BrainPAD. Conclusions These findings provide the first evidence linking tyrosine intake with LC-NA system integrity and its correlation with neuropsychological performance. This study strengthens the role of diet for maintaining brain and cognitive health and supports the noradrenergic theory of cognitive reserve. Within this framework, adequate tyrosine intake might increase the resilience of LC-NA system functioning, by preventing degeneration and supporting noradrenergic metabolism required for LC function and neuropsychological performance.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

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.

Japan has the world’s largest old population ratio, and aging is an urgent societal issue. As global trends seem to be following Japan’s social changes, there is an emphasis on municipalities becoming more age-friendly. Hence, we examine the age-friendliness of 135 Japanese municipalities, selecting 240 resident architectural designers and constructors to assess their municipalities, using the Age-Friendly Cities and Communities Questionnaire (AFCCQ). The findings indicate that Japan lacks “outdoor spaces and buildings.” Additionally, the evaluation of “housing,” “community support and health services,” and “transportation” in populated municipalities in the past five years is significantly higher than those in depopulated ones. Age-friendliness is significantly affected in the AFCCQ total score (hereafter, Score) based on “housing,” “social participation,” “community support and health services,” “transportation” and “financial situation” evaluations. High specificity (0.939) was found when the Score was treated as a marker of depopulation and, therefore, an age-friendly approach is a necessary condition to prevent depopulation. Furthermore, a lack of “communication and information” is observed in municipalities with a higher rate of single-person households aged 65 years and above. Therefore, resident architectural designers’ and constructors’ assessments, combined with the AFCCQ can be a powerful tool in evaluating the age-friendliness of municipalities.

Tumor-associated macrophages (TAMs) play critical roles in the tumor microenvironment (TME), where they are recruited by signals released by cancer cells. Although they have great potential as therapeutic targets for cancer treatment, the dual roles of TAMs in promoting or inhibiting tumor growth, invasion, and metastasis make their function in cancer progression complex. In this review, we provide an overview of the current understanding of TAMs, including their phenotypic diversity, regulatory signaling pathways, and interactions with other cells in the TME. We also discuss the challenges related to the standard isolation protocols of TAMs, inconsistent research results, and translation of TAM knowledge into clinical applications. Additionally, we review the status of clinical trials involving TAMs and potential strategies to overcome the limitations. The future direction of TAM research should focus on developing more targeted therapies that specifically regulate TAM function and non-invasive methods for monitoring TAM activity in cancer patients. A comprehensive understanding of the complex role of TAMs in cancer may lead to the development of more effective treatments and improved outcomes for cancer patients.

Repeated air pollution exposure is one of the major threats to skin health. Air pollution causes skin damage and accelerates skin ageing mainly through oxidative stress mechanisms. Since it is difficult to minimize skin exposure from air pollutants, especially in urban areas, strategies to protect the skin are needed. On the other hand, plant phenolic compounds have been found to be effective in attenuating cellular oxidative stress and inflammation induced by different air pollutants. Therefore, we conducted a 12-week randomized, placebo-controlled, double blind study to assess the efficacy of a polyphenol-enriched dietary supplement (comprised of olive leaf, lemon verbena, rosemary and Sophora japonica extracts) in reducing pollution-induced oxidative stress and in improving different skin parameters related to skin ageing of Caucasian and Asian volunteers living in a polluted urban European area (Milan). One hundred healthy women were recruited and randomized in the placebo or in the test dietary supplement treatment arms. To assess the efficacy of the dietary supplement, the total antioxidant capacity on saliva (FRAP) was determined, as well as the oxidative damage on skin (lipoperoxides content), the skin moisture (corneometry), the trans-epidermal water loss (Tewameter), the skin radiance and the skin colour, (spectrophotometry), the skin elasticity (cutometry), the skin sebum content (sebumeter), and the skin roughness (image analysis). As a result, both inter-group and intra-group analysis proved that the dietary supplement improved all clinical and biochemical monitored parameters, in both Caucasian and Asian individuals. In conclusion, the results of the study indicate a reduced oxidative stress-induced skin damage in both Asian and Caucasian women living in a polluted urban area.

The development of offshore wind farms requires robust bonding solutions that can withstand harsh marine conditions for the easy integration of secondary structures. This paper investigates the durability performance of two adhesives: Sikadur 30 adhesive and Loctite UK 1351 B25 for use in offshore wind environments. Tensile tests on adhesive samples and accelerated aging tests were carried out under a variety of temperature and environmental conditions, including both dry and wet conditions. The long-term effects of aging on adhesive integrity are investigated by simulating the operational life of offshore installations. The evolution of mechanical properties, studied under accelerated aging conditions, provides an important indication of the longevity of structures under normal conditions. The results show significant differences in performance be-tween the two adhesives, highlighting their suitability for specific operating parameters. It should also be noted that for both adhesives, their exposure to different environments (seawater, distilled water, humid climate) over a prolonged period has shown that i) Loctite adhesive has a slightly faster initial uptake than Sikadur adhesive, but the later reaches an asymptotic plateau with a lower maximum absorption rate than Loctite adhesive; and ii) a progressive deterioration in the tensile properties following an exponential function. Therefore, aging behavior results showed a clear correlation with Arrhenius' law, providing a predictive tool for the aging process. Thus, the aging process of the two adhesives follows Arrhenius kinetics.

Aging is the results of several complex and multifactorial processes, where several agents contribute to increase intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms, finely regulated and strictly interconnected, initiating or contributing to biological changes anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic affects. Vitamin D (VitD) is known to have positive impact not only on muscle and bone health, but also on several extra-skeletal districts, due to the widespread presence of VDRs (VDR). VitD and VDR could be molecules potentially targeting the hallmark of aging network. To date, evidence about the potential effect of VitD on the hallmark of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seems to confirm the modulatory effect of VitD on some hallmarks aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

We here investigate the dynamical behavior of a fractional-order predator-prey system with anti-predator behavior and Holling IV type functional response. First we study the non-negativity, existence, uniqueness, and boundedness of solutions to the system from a mathematical analysis perspective. Then, we analyze the stability of its equilibrium points and the possibility of bifurcations using stability analysis methods and bifurcation theory, and prove the existence of a supercritical Hopf bifurcation in the system. After providing numerical simulations to illustrate the conclusions theoretically derived, by summarizing those various analytical results obtained, we finally present three interesting conclusions that can contribute to better understanding and preservation of ecological systems.

The growing worldwide cancer incidence, coupled to the increasing occurrence of multidrug cancer resistance, requires a continuous effort towards the identification of new leads for cancer management. In this work, two C-scorpionate complexes, [FeCl2(κ3-Tpm)] (1) and [Co(κ3-TpmOH)2] (2), (Tpm = hydrotris(pyrazol-1-yl)methane and TpmOH = 2,2,2-tris(pyrazol-1-yl)ethanol), are studied as potential scaffolds for future anti-cancer drug development. Their cytotoxicity and cell migration inhibitory activity are analyzed, and an untargeted metabolomics approach is em-ployed to elucidate the biological processes significantly affected by these two complexes, using two tumoral cell lines (B16 and HCT116) and a non-tumoral cell line (HaCaT). While [FeCl2(κ3-Tpm)] did not display a significant cytotoxicity, [Co(κ3-TpmOH)2] was particularly cy-totoxic against the B16 cell line. While [Co(κ3-TpmOH)2] significantly inhibited cell migration in all tested cell lines, [FeCl2(κ3-Tpm)] displayed a mixed activity. From a metabolomics perspective, exposure to [FeCl2(κ3-Tpm)] is associated with changes in various metabolic pathways involving tyrosine, where iron-dependent enzymes are particularly relevant. On the other hand, [Co(κ3-TpmOH)2] is associated with dysregulation of cell adhesion and membrane structural pathways, suggesting its antiproliferative and anti-migration properties can be due to changes in the overall cellular adhesion mechanisms.

Encephalitis is a condition with a variety of etiologies, clinical presentations and degrees of severity. The causes of these disorders include both neuroinfections and autoimmune diseases in which host antibodies are pathologically directed against self antigens. In autoimmune encephalitis, autoantibodies are expressed in the central nervous system. The incidence of this disease is approximately 4% of all reported cases of encephalitis. Autoimmune encephalitis can be induced by antibodies against neuronal surface antigens such as N-methyl-D-aspartate-activated glutamate receptors (NMDAR), ⍺-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors (AMPAR) or gangliosides GQ1b, DPPX, CASPR2, LGI1, as well as by antibodies against neuronal intracellular antigens. The paper presents a number of both mental and neurological symptoms of autoimmune encephalitis. Moreover, the coexistence of psychoses, neoplastic diseases and the methods of diagnosing autoimmune encephalitis are discussed. Attention was also drawn to the fact that early diagnosis, as well as early initiation of targeted treatment, increases the chance of a successful course of the therapeutic process.

The precise molecular basis of anti-tumor immunity is not yet fully understood, although commensal Bifidobacterium (c-BIF) is expected to be one of the key players in cancer control via antigenic mimicry. We investigated the sequence similarity between c-BIF and cytotoxic T lymphocyte (CTL) epitope peptides against human tumor-associated antigens to better understand the molecular basis of antigenic mimicry. We used two different similarity analyses for this purpose, a linear sequence analysis and a similarity analysis of T cell receptor (TCR)-mediated recognition of CTL epitope peptides on antigen-presenting cells. The linear sequence analysis revealed 3,900 positive numbers of similarity sites between them with 126 mean per peptide and 107 median per peptide, while the TCR-mediated recognition analysis revealed 5,018 positive numbers with a mean of 162 and median of 132 per peptide. These results demonstrated the existence of durable and abundant sequence similarities between c-BIF and CTL epitope peptides, suggesting that the former play a pivotal in inducing cellular and humoral immunity against the latter in the absence of cancer cells via antigenic mimicry.

Background and Aims: The impact of antibody response after direct-acting antiviral (DAA) therapy in hepatitis C virus (HCV)-infected recipients before and after liver transplantation (LT) is still undetermined. Methods: In this observational cohort study, we aimed to explore the association of changes in anti-HCV antibody titers after pre-LT DAA therapy with allograft injury, including biliary complications (BCs) and acute cellular rejection (ACR). Results: A total of 153 cases were enrolled from January 2015 to February 2021. Serum anti-HCV antibody titers were assessed before and after (day 30) LT. Among all recipients, 31/153 (20.3%) had pre-LT DAA therapy (DAA group) and 122/153 (79.7%) did not undergo pre-LT DAA therapy (DAA-naïve group). Higher incidence of post-LT BCs was observed in the DAA group (P = 0.028). Compared with the DAA-naïve group, the DAA group had a significantly higher mean level of anti-HCV titer upregulation (P = 0.0024); furthermore, among the recipients with BCs (n = 28) and ACR (n = 41), those in the DAA group exhibited significantly higher mean levels of anti-HCV antibody titer upregulation (P < 0.005). Conclusion: In conclusion, we speculated that anti-HCV antibody titer upregulation, which might have been induced by restoration of HCV-specific immune responses with pre-LT DAA therapy, were associated with post-LT allograft injury.

Conjugative transposons in Gram-negative bacteria have a significant role in the dissemination of antibiotic-resistance-conferring genes between bacteria. This study aims to genomically characterize plasmids and conjugative transposons carrying integrons in clinical isolates of Klebsiella pneumoniae. Genetic composition of conjugative transposons and phenotypic assessment of 50 multidrug-resistant K. pneumoniae isolates from Tertiary-care Hospital (SQUH), Muscat, Oman was investigated. Horizontal transferability was investigated by filter- mating conjugation experiments. Whole genome sequencing (WGS) was performed to determine the sequence type (ST), acquired resistome and plasmidome of integron-carrying strains. Class 1 integron was detected in 96% of isolates and among integron-positive isolates, 18 stains contained variable regions. Horizontal transferability by conjugation confirmed the successful transfer of integrons between cells and WGS confirmed their presence in conjugative plasmids. Dihydrofolate reductase (dfrA14) was the most prevalent (34.8%) gene cassettes in class 1 integrons. MLST analysis detected predominantly ST-231 and ST-395. BlaOXA-232 and blaCTX-M-15 were the most frequently detected carbapenems and beta-lactamases in sequenced isolates. This study highlighted the high transmissibility of MDR-conferring conjugative plasmids in clinical isolates of K. pneumoniae. Therefore, the wise use of antibiotics and the adherence to effective infection control measures are necessary to limit further dissemination of multidrug-resistant organisms.

Background: Aging rate is affected by genetic changes, epigenetic modifications, oxidative stress, inflammation, lifestyle and environmental factors. In accelerated aging (AA), biological age exceeds the chronological one. Objective: To undertake a critical reappraisal of the AA concept and to reveal its weaknesses and limitations. Methods: We reviewed over 300 recent articles dealing with physiology of brain aging and pathophysiology of neurodegeneration. Results: (1) Organ systems age at different rates, which interferes with application of the AA concept to individual organs. (2) Aging rate can be decelerated due to individual structure–functional reserves built with cognitive, physical training or pharmacological interventions. (3) The AA concept lacks standardised terminology and methodology. (4) Specific molecular biomarkers (MBM) reflect aging. To consolidate the AA theory, researchers should validate numerous MBM candidates. (5) Aging factors, mechanisms and the exact nature of their biological outcomes are not well understood. Conclusion: Although considered as a perspective theory, the AA concept has serious limitations and it requires an update.

Work reviews the new isolated isolated cembranoid diterpene derivatives from species belonging to the family Alcyoniidae, which comprises the genera Sarcophyton, Sinularia, and Lobophytum as well as their biological properties, during 2016–2017. The compilation permitted to conclude that much more new cembranoid diterpenes were found in the soft corals of the genus Sarcophyton sp. (33 new compounds) than in those belonging to the genera Lobophytum (17) or Sinularia (8). Several methods have been used for identifying these new compounds, after extraction with organic solvents and fractionation. The fractions obtained, in some cases, were followed by TLC, and again subjected to chromatographic procedures, including semi-preparative HPLC. Beyond the chemical composition, the biological properties were also evaluated, namely anti-microbial against several Gram-positive and Gram-negative bacteria and fungi, anti-inflammatory and anti-tumoral against several types of cancer cells. Although the biological activities detected in almost all samples, they were not outstanding ones.

Dyslipidemia (Dys) is a disease characterised by abnormally high levels of lipids in the 1 blood. It causes the deposits of lipids on the arterial wall, leading to the insurgence of atherosclerosis, 2 i.e. the increased thickness of arterial walls, which finally increases the risk of cardiovascular diseases. 3 Dyslipidemia is as comorbidity of Type 2 Diabetes Mellitus (T2DM). A set of genes has been associated 4 with dyslipidemia, but examining the regulation of such genes in age and sex is still an open research 5 field. In this study, starting from publicly available databases, we select genes associated with 6 dyslipidemia and we analyse their basal level changes by means of age and sex. Also studying the 7 networks associated to the genes, we identify the rewiring changes showing that there exists a set of 8 genes whose expression changes with age in: artery tibial, artery aorta and blood. Finally, we report 9 about changes associated to gender atributes in the extracted data

Dyslipidemia (Dys) is a disease characterised by abnormally high levels of lipids in the blood. It causes the deposits of lipids on the arterial wall leading to the insurgence of atherosclerosis, i.e. the increased thickness of arterial walls, which finally increases the risk of cardiovascular diseases. Dyslipidemia is a comorbidity of Type 2 Diabetes Mellitus (T2DM). A set of genes has been associated with dyslipidemia, but examining the regulation of such genes in age and sex is still an open research field. In this study, we select from publicly available databases the genes associated with dyslipidemia and analyse changes in the basal level of such genes by age and sex. Moreover, we also distinct differential rewiring of the related gene association network in males and females. Our results show that there exist a set of genes whose expression changes with age in artery tibial, artery aorta and blood. Moreover, there exist significant differences between sex.

The aging populations observed across numerous countries worldwide necessitate a thorough exploration of interventions aimed at promoting healthy aging. As individuals age, they undergo significant physiological changes that impact their functional capacity and often necessitate increased reliance on external support systems. Enhancing the autonomy and well-being of elderly individuals emerges as a critical imperative, serving not only individual interests but also broader societal goals. This review investigates various interventions designed to optimize the health and independence of aging populations, offering insights into effective strategies for promoting healthy aging and mitigating the societal burdens associated with an aging demographic.

PVC items are environmentally friendly as, unlike polyolefins, they are mainly based on chlorine, one of the most abundant elements on earth. However, in the eco-design context, articles' durability plays the crucial role, contributing to the enhancement of their sustainability. In this framework the research on additives capable of increasing the weatherability of outdoor articles is essential. The theory section of the paper reviews the mechanisms of weathering leading to PVC degradation that undermine the durability of items such as window frames or roller shutters. The weathering of PVC items is a complex phenomenon involving photo-chemical and secondary chemical reactions, that yields the formation of conjugated polyene sequences underskin in absence of oxygen and carbonyls in the surface. Here the chain scission of the polymer backbone occurs, bringing the disintegration of the surface of the item and causing the typical discoloration called chalking, especially evident in dark-colored articles. In the experimental section of the paper the effect of different acid scavengers on the item weathering has been studied with natural outdoor and two accelerated exposures, xenon-arc and Q-UV testing devices. Results confirm that some acid scavengers are efficient in preventing chalking, but some are ineffective or even detrimental. Thus, the PVC formulations of durable articles upon weathering still depend on a complex choice of the appropriate ingredients, and several outdoor and indoor accelerated weathering tests are needed to predict the articles' lifetime.

Curcumin is the main secondary metabolites of Curcuma longa and other Curcuma spp, and has been reported to have some potential in preventing and treating some physiological disorders. This study investigated the effect curcumin in inhibiting high-fat diet and streptozotocin (STZ)-induced hyperglycemia and hyperlipidemia in rats. Twenty-six male Sprague-Dawley (SD) rats (170-190 g) were randomly divided into a standard food pellet diet group (Control group), a high-fat diet and streptozotocin group (HF+STZ group), and a high-fat diet combined with curcumin and STZ group (HF+ Cur +STZ group). Compared with the HF+STZ group, the HF+Cur+STZ group exhibited significantly reduced fasting blood glucose (FBG), total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), alanine aminotransferase (AST) and aspartate transaminase (ALT) levels, and liver coefficients; in the livers of these rats, the expression of malondialdehyde (MDA) and Bax was downregulated, whereas that of superoxide dismutase (SOD) and Bcl-2 was upregulated. Moreover, the liver histology of these rats was improved and resembled that of the control rats. These results suggest that curcumin prevents high-fat diet and STZ-induced hyperglycemia and hyperlipidemia, mainly via anti-oxidant and anti-apoptotic mechanisms in the liver.

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.

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.

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.

Calorie restriction (CR) has been shown to prolong the lifespan of humans, but enforcing long-term CR is difficult. Therefore, a compound that reproduces the effect of CR without CR is needed. In this review, we summarize the current knowledge on compounds with CR mimetic (CRM) effects. More than 10 compounds have been listed as CRMs, some of which are conventionally categorized as upstream-type CRMs showing glycolytic inhibition while the others are categorized as downstream-type CRMs that regulate or genetically modulate intracellular signaling proteins. Among these, we focus on upstream-type CRMs and propose their classification as compounds with energy metabolism inhibition effects, particularly glucose metabolism modulation effects. The upstream-type CRMs reviewed include chitosan, acarbose, sodium-glucose cotransporter 2 inhibitors, and hexose analogs such as 2-deoxy-D-glucose, D-glucosamine, and D-allulose, which show anti-aging and longevity effects. Finally, we discuss the molecular definition of upstream-type CRMs.

Antibiotic failure is one of the most worrying health problems worldwide. Nowadays we are facing an international crisis where several issues are involved: new antibiotics are not being discovered any longer, resistance mechanisms become spread in nearly every clinical isolate of bacteria and the appearance of recurrent infections caused by persistent bacteria complicates the overcoming of infections. In this context, it has been explored new anti-infectious strategies against MDR and persistent bacteria as well as the rescue of FDA-approved compounds (drug repurposing). Among the highlighted new anti-infectious strategies we find anti-microbial peptides, anti-virulence compounds, phage therapy and new molecules. On the other hand, as drugs of repurposing that have been described, we have anti-inflammatory compounds, anti-psychotics, anti-helmintic drugs, anti-cancerous and statins.

Counterfeiting and theft have always been problems that incur high costs and results in considerable losses for the international markets. In this research paper, we will address the issue of counterfeiting while using RFID technology in retailer systems or other industries by presenting a new anti-counterfeiting and anti-theft system for the retailer market. This system will address the two above mentioned issues and provide a solution that can save the retailer systems millions of dollars yearly. This proposed system will achieve the objective of preventing or minimising the counterfeiting and theft of tagged products. At the same time, it will provide a strong indication for suspiciously sold or obtained items. Furthermore, we conducted a security analysis to prove the correctness of our protocol on the basis of the strand spaces.

This is an opinion piece based on observations from more than two decades of biomedical data mining insights studying health and disease. It has led me to reevaluate modern life and how lived experiences in many parts of the world are being questioned and now answered through the various technological advances that have taken place in biomedical science. Our mitochondria are multi-faceted and the next generation will need to ensure that they develop a strong understanding from a scientific basis for how they are important to our health. The mind-body connection is also now being investigated through researching the networks of mitochondrial bioenergetics. This article provides a brief introduction to how we can reduce chronic disease burden globally, by introducing a simple first algorithm for healthy aging. This work is aimed to jump start the collection of Algorithms for Healthy Aging (AHA) in the context of global populations in their locally lived generational experiences, which may have underlying scientific bases that are yet to be discovered and validated.

The evolutionary theory of aging, particularly antagonistic pleiotropy (AP), provides an account of the ultimate origins of aging. What remains unclear is the nature of the proximate mechanisms by which AP gives rise to diseases of aging, like cardiovascular disease and Alzheimer’s disease. Damage-centric theories focusing on loss of genetic and cellular function have been proposed, as well as programmatic theories focusing on unwanted gene and cellular function. The latter include the hyperfunction and developmental theory that view aging as the futile continuation, or run-on, of growth and developmental programmes into later life - controlled by nutrient-sensitive pathways like the mechanistic Target of Rapamycin (mTOR) and the linked insulin/IGF-1 signalling (IIS) pathway. Yet neither type of theory has performed well in explaining late-life disease aetiology, particularly with respect to disease onset, presentation and progression. What is proposed in this essay is a new programmatic theory of aging. This essay argues that the emergence of many specific diseases may involve quasi-programmes that are not the result of run-on, but rather are triggered by other factors in late life. Such triggers may be non-programmatic (e.g. infection, mechanical injury) or programmatic. Moreover, the consequent pre-pathological and pathological changes may in some cases trigger further changes, leading to futile and destructive cascades of quasi-programmes and pathology. The origins of triggered quasi-programmes can be traced to biological constraint i.e. the inability of organisms to optimise all functions at once. And, to some extent, the new theory presented here revises the understanding of AP. That is, because any gene can be triggered in an erroneous manner, every gene is potentially an AP gene that risks pathology, though level of risk varies according to constraint. To help validate the theory, we test it against several complex diseases of aging. The new model in this essay attempts to provide a blueprint understanding that, to a certain extent, closes the gap in the causal chain of events between evolutionary causes of aging and the aetiology of age-related diseases. It also helps to explain why certain disorders mimic accelerated aging and how interventions, such as the suppression of IIS and mTOR retard many aspects of aging; notably, though, unlike prior programmatic theories, the new theory is not mTOR-centric. Finally, it provides new perspectives on possible treatment of aging.

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.

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.

Maslinic acid (MA) is a natural triterpene from Olea europaea whose pharmacological functions have been showed. The objective of this study was to examine MA effect on cell viability (by MTT assay), reactive oxygen species (ROS levels, by flow cytometry) and key anti-oxidant enzyme activities (by spectrophotometry) in murine skin melanoma (B16F10) cells compared to healthy cells (A10). MA induced cytotoxic effects in cancer cells (IC50 42 µM) whereas no effect was found in A10 cells treated with MA (up to 210 µM). In order to produce a stress situation in cells, 0.15 mM of H2O2 were added. Under stressful conditions, MA protected both cell lines against oxidative damage, decreasing intracellular ROS, being higher in B16F10 than in A10 cells. The treatment with H2O2 and without MA produced different responses in anti-oxidant enzymes activities depending on cell line. In A10 cells, all enzymes were up-regulated, but in B16F10 cells only superoxide dismutase, glutathione S-transferase and glutathione peroxidase increased their activities. MA restored the enzyme activities to similar levels than control group in both cell lines, highlighting that in A10 cells the highest MA doses induced values lower than control. Overall, these findings demonstrate the great anti-oxidant capacity of MA.

Aging causes various degenerative diseases in the older adult population. Senescence, a state of permanent cell-cycle arrest accompanied by the production of various pro-inflammatory factors known as senescence-associated secretory phenotype (SASP), is considered a significant contributor to the aging process and its chronic diseases. Ample evidence showed that various stressors could induce senescence, including DNA damage, telomere shortening and damage, activation of oncogenes, and mitochondrial dysfunction. Numerous credible findings indicate that environmental agents can induce senescence, including UV radiation, a high-fat diet, heavy metal exposure, and cigarette smoke. These findings posed the possibility that many more environmental agents may induce senescence and accelerate aging but remain unidentified. Senescence also becomes more intriguing due to its promising future as a pharmacological target to blunt the detrimental effects of aging and prevent aging-related diseases, either by eliminating the senescent cells or by controlling the SASP. On the other hand, investigating senescence has become more intricate due to the need for a multi-marker approach and translation in vivo analysis. This review will discuss senescence and its biomarkers, how to identify gerontogens in vivo, and also the development of senotherapy that targets senescent cells.

The biological aging, characterized by changing in metabolism and physicochemical properties of cells, has an impact on public health. Environment and lifestyle including factors like diet and physical activity seems to play a key role in healthy ageing. Several studies have shown that regular physical activity can enhance antioxidant defence mechanisms, including the activity of enzymes such as superoxide dismutase (SOD), catalase, and glutathione peroxidase. However, intense or prolonged exercise can also lead to an increase in ROS production temporarily, re-sulting in oxidative stress. This phenomenon is referred as "exercise-induced oxidative stress". The relationship between physical activity and oxidative stress in aging is complex and depends on various factors such as the type, intensity, duration, and frequency of exercise, as well as in-dividual differences in antioxidant capacity and adaptation to exercise. In this review, we ana-lyzed what is reported from several authors regarding the role of physical activity on oxidative stress in aging process as well as the role of hormesis and physical exercise as tools for preven-tion and treatment of sarcopenia, an aging related disease. Finally we reported what has recently been studied in relation to the effect of physical activity and sport on aging in women

Adipose tissue undergoes changes with aging, leading to increased adiposity, inflammatory cell infiltration, reduced angiogenesis, heightened oxidative stress, and alterations in its metabolic function. Regular exercise has been recognized as a powerful intervention that can positively influence adipose tissue health and mitigate the effects of aging. However, the molecular mechanisms underlying the benefits of regular exercise on aging adipose tissue function remain poorly understood. Adipokines released through regular exercise play a potential role in mitigating adipose tissue aging, enhancing the metabolism of glucose and lipids, reducing inflammation and fibrosis, and promoting fat browning and thermogenesis. The goal of this review is to offer a comprehensive overview of the benefits of regular exercise in addressing the age-related decline in adipose tissue function. The significance of regular exercise in mitigating metabolic disorders associated with aged adipose tissue will be discussed.

We explored how dietary behaviors (sucrose, fructose, sodium, and potassium consumption) and endured psychological stress in young adult males and females impact the vascular aging index (VAI) and CVD risk by mid-life. Data were obtained from the Coronary Artery Risk Development in Young Adults Study, an ongoing longitudinal study. Included participants (n=2,656) had un-dergone carotid artery ultrasound at year 20 allowing VAIs to be calculated. Demographics, di-etary data and depression scores were obtained at baseline and year 20. Regression analyses were used to assess the predictors of VAI. Cox regression analyses were conducted to assess the risk of CVD, stroke and all-cause mortality. Predictors of vascular aging were found to be sex-specific. In females, CES-D scores at baseline were positively associated with VAI (B-weight=0.063, p=0.015). In males, sodium intake at year 20 positively predicted VAI (B-weight=0.145, p=0.003) and potassium intake inversely predicted VAI (B-weight=-0.160, p<0.001). BMI significantly predicted CVD, stroke, and death. Fructose consumption at year 20 was a significant predictor of CVD risk while having high blood pressure at baseline was signif-icantly associated with stroke risk. Our findings support the promotion of nutrient- specific be-havior changes to prevent vascular aging in early adulthood and CVD risk in mid-life.

We conducted a research study to create groundwork for personalized solutions within skin aging segment. This test utilises genetic and general laboratory data to predict individual susceptibility of weak skin characteristics, leveraging on the research on genetic polymorphisms related to skin functional properties. A cross-sectional study was conducted in collaboration between the Private Clinic Medicina Practica Laboratory (Vilnius, Lithuania) and the Public Institution Lithuanian University of Health Sciences (Kaunas, Lithuania). 370 participants agreed to participate in the project. The median age of respondents was 40, with a range of 19 to 74 years. After the literature search, we selected 15 polymorphisms of the genes related to skin aging subsequently distributed for different skin functions: SOD2(rs4880), GPX1(rs1050450), NQO1(rs1800566), CAT (rs1001179), TYR (rs1126809), SLC45A2 (rs26722), SLC45A2 (rs16891982), MMP1(rs1799750), ELN (rs7787362), COL1A1(rs1800012), AHR (rs2066853), IL6 (rs1800795), IL1Beta (rs1143634), TNF-α (rs1800629), AQP3(rs17553719). RT genotyping, blood count and immunochemistry results have been analysed using statistical methods. Obtained results showed significant associations among genotyping models and routine blood screens. These findings demonstrate the personalized medicine approach for aging segment and further add onto the growing field of literature. Further investigation is warranted to fully understand the complex interplay between genetic factors, environmental influences, and skin aging.

Abstract: Background: Cancer and cancer treatments may affect aging processes, altering the trajectory of cognitive aging, but extant studies are limited in interval of assessment (2-5 years). We studied cognitive performance in a cohort of survivors and controls utilizing cross-sectional cognitive performance data from age 60 to 89 years as an indicator of potential aging trajectories and contrasted these trends with longitudinal data collected over two years. Methods: Female breast cancer survivors who had been diagnosed and treated at age 60 or older and were 5– to 15-year survivors (N=328) and non-cancer controls (N=158) were assessed at enrollment and at 8, 16 and 24 months with standard neuropsychological tests and comprehensive geriatric as-sessment. Results: Cross-sectional baseline analysis found the expected inverse association of age with cognition in both groups, with survivors performing lower than controls in learning and memory (LM) but not in attention, processing speed and executive function (APE). Younger survivors, i.e., those under 75 years of age, exhibited early decline in performance in both LM and APE compared to controls, with no differences between older survivors and controls, which tracked with deficit accumulation trends. Conclusion: Differences between survivors and controls were prominent in younger survivors, as was deficit accumulation, suggesting a mediating effect on cognition. Deficit accumulation may represent a modifiable risk factor in cancer survivorship that may be targeted for prevention and intervention.