Biology and Life Sciences

Abstract: Prostate cancer is strongly associated with aging, but the biological mechanisms linking aging to tumor progression remain incompletely defined. Beyond accumulated genetic alterations, aging reshapes the prostate tissue microenvironment through cellular senescence, chronic low-grade inflammation, immune dysfunction, stromal remodeling, metabolic stress, and impaired tissue repair. These processes contribute to inflammaging, a persistent inflammatory state that may create a permissive microenvironment for prostate tumor initiation, progression, immune evasion, and treatment resistance. Senescent epithelial and stromal cells can secrete cytokines, chemokines, growth factors, matrix-remodeling enzymes, and extracellular vesicles through the senescence-associated secretory phenotype (SASP). In parallel, immune aging alters T-cell subsets, myeloid cells, macrophages, and other immune populations, affecting anti-tumor surveillance and tumor-promoting inflammation. This review summarizes current knowledge of cellular senescence and inflammaging in prostate cancer, with emphasis on SASP, Th17/Treg imbalance, IL-17/IL-23-related inflammatory signaling, myeloid remodeling, stromal aging, metabolic stress, and immune–stromal–epithelial crosstalk. We also discuss how aging-associated inflammatory networks may influence tumor progression, therapeutic response, and emerging opportunities for cytokine modulation, senescence-directed therapy, metabolic intervention, and biomarker-guided approaches. Understanding the aging prostate microenvironment may reveal new strategies to prevent or delay aggressive prostate cancer progression in older men.

Abstract: Diet and lifestyle are modifiable determinants of oxidative balance through exposure to antioxidant and pro-oxidant factors. The oxidative balance score (OBS) is a composite index reflecting the balance between these exposures, with higher scores indicating a pre-dominance of antioxidant factors. We examined three OBSs (nutrient-, food-, and life-style-based) and their combined versions (nutrient-lifestyle and food-lifestyle) across clinical subgroups, and their associations with biomarkers of oxidative stress, inflammation and metabolic function. A total of 44 older adults were enrolled and stratified into three subgroups (16 healthy, 14 hyperlipidemic, and 14 post–myocardial infarction). Each participant completed a ques-tionnaire, a three-day food record and a blood test. OBSs were calculated based on 15 nutrients, 9 food groups and 2 lifestyle components. Correlations and multiple linear regression analyses were performed to examine associations between OBSs and biomarkers: plasma total antioxidant capacity TEAC and FRAP, C-reactive protein (CRP), HDL-cholesterol, alanine aminotransferase (ALT), aspartate aminotransferase (AST). The nutrient-based OBS (OBSN) was significantly associated with higher HDL-cholesterol (β = 0.033; p = 0.045), lower ALT (β = −1.53; p < 0.001), and lower AST (β = −0.85; p = 0.002). Similar associations were observed for the nutrient-lifestyle OBS (OBSN-L) (adjusted ALT β = -1.48; p < 0.001; β = -0.79; p = 0.001). No significant associations were observed for TEAC (β = 5.295 p = 0.535) and FRAP (β = -4.640, p = 0.475), nor for CRP (β = 0.046, p = 0.347). OBSF and OBSF-L were not associated with any circulating biomarkers. Higher nutrient-based OBSs (with and without lifestyle integration) were independently associated with higher HDL cholesterol and lower liver transaminase levels in older adults at high cardiovascular risk. OBSs may help capture dietary and lifestyle patterns associated with cardiometabolic health.

Abstract: Aging is the breakdown of life over time. A comprehensive, integrated, and universal mechanism to explain aging is lacking. We propose a unifying model reconciling existing theories with new ideas, organized around a concept we term “intropy”: the capacity of encoded information to produce and sustain functional and purposeful order. This model maintains aging results from the progressive loss of intropy through corruption of information-bearing nucleic acid that scrambles the chemical memory required to order life’s processes. The corruption decreases the efficiency of replicational, transcriptional, translational, and enzymatic outputs, amplifying functional inefficiency up a hierarchy of biological organization, from genome to organism. To sustain order against nearly infinite environmental stochasticity, evolution begot phenotypic diversity to protect and safeguard the transmission of relatively uncorrupted intropy to progeny (a “prime directive”), the original carrier left to continue a descent to a disordered state. Death results after crossing an irreversible efficiency threshold in which functional order is catastrophically lost and disorder rapidly rises, consistent with thermodynamic laws. While many cellular components sustain environmental damage, only corruption of nucleic acid, the sole irreplaceable template directing biological order, propagates functional disruption across every level of life's hierarchy. The informational corruption underlying aging reframes age-associated disease as a consequence of disordered biological instruction, thereby revealing nucleic acid change as the common process uniting aging, disease, and evolution. The theory reveals ways to significantly preserve order via engineered intropic protection, rendering the carrier relatively amortal.

Abstract: Background: Central arterial stiffness assessed by carotid-femoral pulse wave velocity (PWVc-f) strongly predicts cardiovascular risk. We examined associations of objec-tively measured physical activity, sedentary behavior, and functional fitness with PWVc-f in community-dwelling older adults. Methods: The study included 170 older adults (124 women; 64–91 years). Moderate-to-vigorous physical activity (MVPA) and sedentary behavior were assessed by accelerometry, functional fitness by the Fullerton Functional Fitness Test (composite score), and PWVc-f by applanation tonometry. As-sociations were examined using correlation, hierarchical linear regression, and logistic regression analyses. Results: Elevated arterial stiffness (PWVc-f >10 m/s) was present in 62.3% of participants. PWVc-f associated with all functional fitness measures, in-cluding the composite score (ρ=−0.338, p< 0.001), but not with MVPA or sedentary be-havior. High functional fitness associated with lower odds of elevated PWVc-f in un-adjusted analyses (OR=0.39, 95% CI 0.20–0.78; p=0.007), but this was no longer signifi-cant after adjustment for age, sex, and anthropometric/clinical characteristics. Neither MVPA nor sedentary behavior predicted PWVc-f. Age remained the only independent correlate across all models. Conclusions: Functional fitness showed stronger unad-justed associations with PWVc-f than MVPA or sedentary behavior. However, these associations were largely explained by age, indicating that functional fitness and PWVc-f primarily reflect shared age-related physiological processes.

Abstract: Physical performance can be understood as a continuum throughout the life course, ranging from peak athletic ability in early life to the preservation of mobility and functional independence in old age. This narrative review explores whether the biological and genetic pathways involved in athletic performance might also modulate the risk of geriatric motor dysfunctions (GMDs), including sarcopenia, frailty and lower-limb weakness. The available evidence suggests a convergence between performance and motor decline in mechanisms such as mitochondrial function and mitophagy, anabolic-catabolic balance, oxidative stress and low-grade chronic inflammation, neuromuscular integrity, satellite cell function, mechanotransduction, myokine-mediated signalling, and the gut-muscle axis. Although classic candidate genes such as ACTN3 or ACE have been useful for formulating mechanistic hypotheses, genome-wide association studies support a highly polygenic architecture for strength, lean mass, muscle weakness and frailty. These effects are strongly modulated by the exposome, particularly by physical activity, nutrition and comorbidities. Overall, the relationship appears consistent with predominantly beneficial pleiotropy, although context-dependent effects cannot be ruled out. Genetics may influence functional reserve and decline trajectories, but exercise, particularly strength and power training, along with adequate nutrition and the management of comorbidities, remain the primary strategies for preventing or delaying sarcopenia, frailty and lower-limb weakness.

Abstract: Replicative senescence links telomere shortening to irreversible proliferative arrest and is widely recognized as a major tumor-suppressive mechanism. At the organismal level, however, progressive accumulation of senescent cells contributes to tissue dysfunction, chronic inflammation, and aging. Accumulating evidence suggests that telomere shortening influences chromatin organization and subtelomeric transcription through mechanisms that remain incompletely understood. Building upon the telomere position effect model of cellular senescence and the subtelomere-telomere theory of aging, this review proposes a chromatin-sensing telomere framework in which telomere shortening induces senescence through epigenetic and transcriptional changes at chromosome ends. Central to this model is TERRA, a long non-coding RNA that regulates telomeric chromatin structure, telomere maintenance, and DNA-damage responses. The H3K4 methyltransferase MLL/KMT2A is a key regulator of TERRA transcription. MLL associates with telomeric chromatin in a telomere length-dependent manner and promotes TERRA transcription through H3K4 methylation. Shelterin components, particularly TRF2, function as repressors of TERRA, and we propose that telomere shortening progressively alters shelterin organization and telomeric chromatin topology, thereby reducing access of MLL and RNA polymerase II to subtelomeric promoters. A biphasic model of TERRA regulation emerges in which early TERRA upregulation observed in aging tissues transiently promotes telomere protection, while later critical shortening of TERRA-dominant telomeres drives global TERRA repression and contributes to telomere dysfunction and senescence. This framework provides a mechanistic link between telomere shortening, chromatin regulation, and quasi-programmed aging.

Abstract: Older adults with type 2 diabetes mellitus (T2DM) may exhibit early neuromuscular impairment, but the relative contribution of functional performance, mechanical capacity, body composition, and metabolic status remains unclear. This matched cross-sectional study compared 31 older adults with T2DM and 31 non-diabetic controls matched by age, sex, and body mass index (BMI). Participants completed assessments of physical function, sit-to-stand (STS)-derived muscle power, lower-limb force–velocity profiling during leg press, dual-energy X-ray absorptiometry, and fasting blood analyses. Between-group differences were examined using independent-samples t-tests, while discriminant and receiver operating characteristic (ROC) analyses were used as exploratory approaches to examine within-sample differentiation of T2DM status. Compared with controls, participants with T2DM showed longer 5-STS time (p = 0.001) and lower absolute and relative STS power (both p ≤ 0.01). In contrast, leg-press maximal force (F0) and maximal power (Pmax) did not differ between groups, while maximal and optimal velocity were higher in the T2DM group (both p = 0.026). T2DM group also showed lower peripheral fat mass, a higher android-to-gynoid ratio, higher fasting glucose, and lower insulin and HOMA-β values. Exploratory classification analyses suggested that a combined model including relative STS power, V₀, HOMA-β, and android-to-gynoid ratio showed higher within-sample discrimination than relative STS power or leg-press maximal power alone. These findings suggest that STS-derived functional power may provide complementary information to leg-press force–velocity profiling when characterizing functional status in older adults with T2DM.

Abstract: Background/Objectives: Osteoarthritis (OA) is strongly associated with mitochondrial dysfunction, oxidative stress, and the accumulation of mitochondrial DNA (mtDNA) alterations, which contribute to impaired cellular homeostasis and reduced regenerative potential. In this study, we systematically characterized mtDNA heteroplasmy and variant distribution across bone marrow-derived mesenchymal stromal cells (MSCs), induced pluripotent stem cells (iPSCs) and induced MSCs (iMSCs) derived from OA pa-tients and healthy donors. Methods: Ultra-deep mitochondrial genome sequencing was integrated with transcriptomic and miRNome analyses to investigate mitochondrial remodeling during cellular reprogramming and its interaction with nuclear-encoded mitochondrial pathways. Results: OA-derived MSCs exhibited a markedly increased heteroplasmic burden and accumulation of non-synonymous variants, particularly within OXPHOS-related genes, including MT-ND1, MT-ND2, MT-ND3, MT-ND5, MT-ATP8, MT-CO1, and MT-RNR1/2. Reprogramming into iPSCs and subsequent differentiation into iMSCs resulted in the progressive elimination of pathogenic mtDNA variants, in-cluding m.7913C>T and m.7821G>A, as well as substantial reduction of heteroplasmic hotspots, indicating a purifying mitochondrial remodeling process. Multi-omic analysis further revealed coordinated deregulation of mitochondrial-associated nuclear genes and competing endogenous RNA regulatory networks involving lncRNAs MEG3 and SNHG14, along with multiple mitochondria-related miRNAs. These findings suggest post-transcriptional regulation of mitochondrial adaptation in iMSCs. Conclusion: Col-lectively, our findings demonstrate that cellular reprogramming promotes mitochondrial genomic reorganization and indicates a potential metabolic recalibration. These results support the utility of iMSCs as a relevant model for studying OA-associated mitochondrial alterations and as a potential tool for regenerative approaches in OA.

Abstract: Background and Objectives: Functional decline is a major determinant of disability, caregiver burden, and loss of independence in behavioral variant frontotemporal dementia (bvFTD). Although bvFTD is characterized by early and rapidly progressive deterioration in everyday functioning, longitudinal multimodal predictors of this decline remain insufficiently understood. The present study aimed to identify cognitive, behavioral, personality, and neuroimaging predictors of longitudinal functional deterioration in bvFTD using an integrated multimodal framework over a 12-month follow-up period. Methods: Twenty-seven patients diagnosed with bvFTD were recruited from the 2nd Neurology Clinic at the “AHEPA” University Hospital in Thessaloniki, Greece, and underwent comprehensive face-to-face neuropsychological assessment for the evaluation of a wide range of cognitive domains, alongside caregiver-based informant evaluations of behavioral disturbances, personality changes, and functional abilities, at baseline, 6 months, and 12 months. Functional status was assessed using the Disability Assessment for Dementia (DAD) as the primary outcome, while the Frontotemporal Dementia Rating Scale (FRS) served as a secondary measure. Brain perfusion single-photon emission computed tomography (SPECT) was acquired only at baseline, with regional cerebral blood flow quantified using a Brodmann area (BA)–based approach. Repeated-measures analysis of variance (ANOVA) was used to characterize longitudinal changes across cognitive, behavioral, personality, and functional domains, while linear mixed-effects (LME) models were applied to identify predictors of functional trajectories and sources of inter-individual variability in functional outcomes. Results: Significant progressive decline in functional abilities was observed over the 1-year follow-up period, consistent with an aggressive and rapidly deteriorating clinical course in bvFTD. Functional impairment affected both basic and instrumental activities of daily living, with a more pronounced decline in instrumental activities. Based on the final LME model, greater apathy-related (negative) behavioral symptoms, global cognitive impairment, attentional and processing speed deficits, and impaired inhibitory control were independently associated with poorer longitudinal functional outcomes. At the neuroimaging level, reduced perfusion in the right BA 24 within the anterior cingulate cortex was also significantly associated with greater loss of functional independence over time. Conclusions: Longitudinal functional decline in bvFTD reflects the combined disruption of behavioral regulation, global cognition, executive control, and frontal–cingulate network integrity. These findings support a multidimensional model of functional deterioration and highlight clinically actionable markers for prognosis, stratification, and personalized care in bvFTD.

Abstract: A steady increase in the elderly demographic, particularly those 85+ in age, has given rise to an elevation in global prevalence of neurodegenerative disorders, such as Alzheimer's and Parkinson's diseases, and underscores an urgent need for novel, preventive, and disease-modifying strategies. Marine ecosystems represent a prolific source of bioactive compounds, among which xanthophyll carotenoids—oxygenated derivatives including astaxanthin, fucoxanthin, and canthaxanthin—have emerged as compelling candidates for neuroprotection. These compounds exhibit superior bioavailability and blood-brain barrier permeability compared to hydrocarbon carotenoids, attributed to their polar functional groups. Their potent bioactivity stems from a multifaceted ability to modulate core pathological processes: directly quenching reactive oxygen species, activating the Nrf2-mediated antioxidant response, inhibiting NF-κB-driven neuroinflammation, and interfering with the aggregation of toxic proteins like amyloid-β and α-synuclein. This review evaluates the preclinical and clinical evidence supporting the neuroprotective potential of these three marine xanthophylls. Astaxanthin demonstrates the most robust and extensive evidence base, from cellular models to human cognitive trials. Fucoxanthin shows parallel promise with unique effects on mitochondrial biogenesis, while canthaxanthin remains significantly understudied despite its strong antioxidant profile. We further discuss the translational challenges of bioavailability and formulation, highlighting innovative delivery systems, and propose future research directions to harness these marine-derived compounds for promoting brain health and mitigating age-related cognitive decline.

Abstract: Natto is a traditional Japanese food made from fermented soybeans and is a side dish, popular in eastern and northern Japan. Recent studies have suggested a notable link between natto consumption and reduced mortality rates, alongside increased resilience to various stressors and diseases in both humans and model organisms, such as the nematode, Caenorhabditis elegans. Natto is rich in four bioactive components for healthy aging and longevity: bacterial vitamin K2 (menaquinone-7), which supports cardiovascular and bone health; spermidine, known for promoting autophagy and providing anti-inflammatory benefits; the probiotic Bacillus subtilis, which enhances gastrointestinal health; and isoflavone, a plant estrogen. Although there is no officially recommended value set for each component, one serving of natto (50 g) provides significant quantities of vitamin K2 (429%), probiotics (200%), spermidine (625%), and isoflavones (73%) compared to the effective dose in clinical trials and research experiments. Clinical studies have shown no adverse effects of regular natto consumption in healthy individuals, indicating its potential benefits when integrated into a balanced diet. However, caution is advised for individuals with specific health conditions, such as bleeding disorders, soybean allergies, or opportunistic infections, making it essential to consider personal health before incorporating natto into their diet. Taken together, natto has outstanding properties as a food, not only with its bioactivities but also its ability to induce phytohormesis (plant-induced hormesis). This review critically examines the benefits of natto in promoting healthy aging and longevity.

Abstract: Blood is often used either as a source of individual biomarkers or as input for scalar immune-age and biological-age models. This study tests a different question: whether blood-derived longitudinal measurements can be represented as a structured homeostatic state space. A rebuilt blood HRSM framework was applied to a primary repeated-measures IMM-AGE cellular object and to supporting transcriptomic blood branches. The state vector was defined by reserve-like support, trajectory recoverability, coherence or volatility control, and retained persistence. In the primary IMM-AGE object, published immune age aligned strongly with higher retained persistence, lower reserve-like support, and lower coherence, while recoverability was weak. The strongest single cellular driver was naive CD8⁺ T-cell decline, consistent with established immune-ageing biology. Longitudinal tests showed that temporal memory was strongest in the persistence axis, with reserve-like support moving in the opposite direction. A subject-level persistence index indicated stronger preservation of the 2008 blood-state configuration in younger baseline subjects. Joint HRSM entropy declined across time, suggesting compression of the accessible multivariate blood-state distribution. Sensitivity checks preserved the central ageing polarity after removal of PD1 from the persistence map, use of a reduced core map, and removal of broad lymphocyte-bulk support terms. Supporting GSE213313 analyses provided a completed transcriptomic blood branch with negative controls, comparators, and cross-dataset validation against GSE324831. Cross-dataset portability was strongest for support, recoverability, and coherence families, whereas persistence was not portable as a fixed molecular family and was better interpreted as a context-sensitive behaviour. The results support blood HRSM as a systemic gateway representation of immune ageing, not as a replacement for existing immune-age clocks and not as a universal molecular-memory claim.

Abstract: Dementia represents a growing global public health challenge, driving the rapid expansion of educational interventions aimed at improving awareness and promoting risk-reduction behaviours. Despite this growth, existing research demonstrates a persistent gap between knowledge acquisition and meaningful behavioural change. This paper presents a realist-informed conceptual analysis and proposes an integrative conceptual framework for evaluating the real-world effectiveness of digital dementia education. Integrating health literacy theory, the Capability–Opportunity–Motivation Behaviour (COM-B) model, and implementation science, the framework conceptualises dementia education as a dynamic, multi-component process involving resource availability, user engagement, interpretative engagement, behavioural readiness, contextual influences, and real-world outcomes. Particular emphasis is placed on interpretative engagement, grounded in constructivist and sensemaking perspectives, as a key mechanism linking exposure to educational content with behavioural intention and action. The paper identifies critical limitations in current evaluation approaches, including overreliance on knowledge-based outcomes and insufficient consideration of contextual, emotional, and implementation influences. By advancing a user-centred and context-sensitive framework, this study contributes to the development of more theoretically informed and implementation-oriented approaches for evaluating digital dementia risk-reduction education, particularly among midlife populations.

Abstract: Vascular aging is a key factor in late-life health issues, including cardiovascular disease, stroke, and organ decline. It results from accumulated molecular, cellular, and structural damage like endothelial dysfunction, smooth muscle maladaptation, extracellular matrix failure, calcification, inflammation, and barrier breakdown. This accumulated damage interacts in ways that cause lasting changes to vascular mechanics and permeability. This chapter categorizes vascular damage into distinct physiologically recognizable groups, distinguishing root causes from signaling responses and emphasizing persistent structural and biochemical damage over transient dysregulation. This explains the limited durability of many signaling therapies and suggests that direct damage repair may provide more lasting and comprehensive benefits. We review evidence on endothelial cells, smooth muscle, extracellular matrix, mineralization, immune-vascular interactions, and hemodynamics, focusing on mechanisms that cause long-term damage. We discuss therapeutic strategies and risks of manipulating signaling pathways that vary across tissues. Finally, we explore the need for biomarkers reflecting specific vascular damage, advocating for a divide-and-conquer approach with targeted repairs and suitable endpoints to improve interventions that preserve vascular function.

Abstract: Ageing remains one of biology’s most fundamental unresolved questions. Existing explanations often attribute ageing to stochastic damage accumulation, adaptive programmes, or interacting hallmarks, yet none fully explains why ageing emerges so broadly in organisms that undergo development. Here, I introduce the Double Code Hypothesis of Ageing, which frames ageing as a consequence of life’s dual inheritance system: the genome and the epigenome. In this manuscript, ‘code’ is used in a computer-science-like sense, closer to source code than to the specialised meaning used in code biology: an organised set of biological instructions whose effects depend on being read, interpreted, maintained, and executed by cellular machinery.I propose that ageing is not merely the progressive accumulation of epigenetic noise within an individual, but the consequence of an inherent instability in a dual inheritance system whose two informational layers must remain functionally aligned across cellular and organismal generations. The relative stability of the genome allows long-term information preservation, whereas the plasticity of the epigenome enables development, differentiation, adaptation, and the emergence of complex phenotypes, but also makes this layer vulnerable to cumulative misalignment.Within this framework, ageing is interpreted as the individual-level cost of an information-management architecture that preserves and renews biological information across generations. In complex organisms, mitotically dividing cells progressively lose or misalign epigenetic information, whereas meiotic/germline-associated processes can restore or re-establish a functional genome–epigenome configuration for the next generation. This falsifiable framework offers experimental predictions in model systems such as Schizosaccharomyces pombe and provides a mechanistic explanation for why ageing exists.

Abstract: The concept of inflammaging — referring to the persistent, low-grade inflammatory state that accompanies biological ageing — has progressively positioned itself as a unifying framework for understanding age-related chronic disease. Unlike acute inflammation, which is adaptive, transient, and fundamentally protective, inflammaging reflects a persistent dysregulation of immune signalling. Its hallmarks include failure to resolve inflammatory signals, alongside mitochondrial decline and the gradual erosion of tissue homeostasis driven by persistent cytokine activity. Increasing evidence suggests that inflammaging is not merely a consequence of ageing, but rather an active systems-level process capable of reshaping metabolic, vascular, neurological, and musculoskeletal physiology. Persistent inflammatory activation contributes to frailty, cardiovascular disease, neurodegeneration, sarcopenia, metabolic dysfunction, and osteoarthritis through interconnected molecular and cellular pathways involving immunosenescence, cellular senescence, oxidative stress, inflammasome activation, and epigenetic remodelling [1]. Recent advances in geroscience have reframed inflammation as a multidirectional biological network integrating immune, endocrine, metabolic, microbiological, and biomechanical signalling. This perspective moves beyond reductionist cytokine models and instead conceptualises inflammation as a distributed regulatory architecture operating across tissues and organ systems. Within this framework, chronic disease may emerge not solely from isolated organ pathology, but from progressive failure of intersystem communication and adaptive resilience [2]. This invited review examines the biological foundations of inflammaging, with particular emphasis on immunosenescence, senescence-associated secretory pathways, mitochondrial dysfunction, inflammasome biology, cytokine network dynamics, and epigenetic regulation. We propose that inflammaging may be best understood as a form of multiscale biological interface failure in which persistent inflammatory signalling progressively destabilises tissue integration across physiological systems. Such a framework may facilitate the development of more precise biomarkers, systems-oriented therapeutic strategies, and translational approaches aimed at extending healthspan rather than merely prolonging survival.

Abstract: Telomeres and the extracellular matrix (ECM) are often studied as distinct contributors to aging and chronic diseases, yet growing evidence suggests they are deeply interconnected. This review explores the relationship between these two systems in both directions. Telomere shortening, shelterin defects, and loss of telomerase activity can promote senescence, stress responses, myofibroblast transition, and progressive matrix deposition. In turn, stiffness of the ECM, collagen-rich environments, and hyaluronan-linked signaling can shape telomerase activity, proliferative capacity, and telomere-associated damage responses. We bring together evidence from genetic mouse models, mechanistic cell-based studies, and human tissue analyses across the lung, kidney, vasculature, and heart to examine how telomere dysfunction and ECM remodeling influence one another during aging and disease progression. We focus on epithelial cells, fibroblasts, smooth muscle cells, and tubular cells, and discuss key pathways linking telomere biology and ECM regulation, including TRF1, TERT, TGF-β, cGAS–STING, VCAM-1, and mechanotransduction signaling. Taken together, the current findings suggest that telomere dysfunction is not only a marker of tissue aging but it is also an active driver of persistent ECM remodeling and fibrosis, while signals from the ECM can in turn influence telomere maintenance and cellular senescence. This bidirectional relationship provides a clearer framework for understanding how age-related cellular damage progresses into chronic tissue scarring.

Abstract: Sarcopenia is characterized by progressive loss of skeletal muscle mass and function and is a major contributor to frailty, disability, and mortality in older adults. Store-operated calcium entry (SOCE) is a crucial regulator of skeletal muscle calcium homeostasis, and impaired SOCE has been linked to age-related muscle weakness. Here, we investigated the role of the synaptophysin family member synaptophysin-like protein 2, also known as mitsugumin 29 (MG29/SYPL2) in regulating SOCE, muscle structure, and lipid signaling during aging. Using knockout mice (mg29−/−) as a model of accelerated sarcopenia, in combination with RNA interference against MG29/SYPL2 in adult muscle and primary myotubes, we quantified changes in muscle morphology, contractile function, SOCE activity, and targeted lipidomic profiles. We found that reduced MG29/SYPL2 expression leads to decreased muscle fiber cross-sectional area, reduced specific force, blunted SOCE, and marked alterations to membrane cholesterol content as well as fatty acid–derived lipid mediators. Cholesterol depletion by methyl-β-cyclodextrin in wild-type myotubes produced similar SOCE defects as those observed in aged wild-type and young mg29−/− muscles, indicating that MG29/SYPL2-dependent maintenance of membrane cholesterol is required for normal SOCE. Acute MG29/SYPL2 knockdown also modified myogenic differentiation, expression of calcium-handling and stress-response genes, and the release and consumption of specific polyunsaturated fatty acid–derived lipid mediators. Together, these findings identify MG29/SYPL2 as a critical regulator of SOCE and lipid signaling in skeletal muscle and suggest that its age-related decline contributes to sarcopenia by disrupting triad membrane organization and excitation-contraction coupling.

Abstract: 1) Background: Coumestrol is a bioactive compound that inhibits HASPIN activity and prevents tau and H3 phosphorylation. Oral ingestion of CBSs increases blood testosterone levels, which decline with age causing late-onset hypogonadism. Oral ingestion of coumestrol-rich bean sprouts (CBSs) has been shown to suppress the onset of Alzheimer’s disease in 5xFAD mice and the onset of colon cancer in APC^min/+ mice. 2) Methods: We investigated the effect of oral ingestion of CBSs on the progression of aging in male senescence-accelerated prone 1 (SAMP1) mice allowed voluntary exercise or no exercise. The SAMP1 mice were divided into two groups fed either a standard diet or a diet including bean sprouts from 12 to 18 weeks of age. Each group was divided into two groups with voluntary exercise or no exercise. 3) Results: Voluntary exercise accelerated aging-related declines in blood testosterone levels, nerve growth factor levels, and spatial working memory, and oral ingestion of CBSs suppressed these age-related phenotypes, regardless of exercise. 4) Conclusion: Ingestion of CBSs prevented aging-related phenotypes in the experimental mice. A detailed analysis of the molecular mechanisms of coumestrol will be useful for understanding aging and preventing age-related diseases such as cancer, Alzheimer’s disease, and LOH.

Abstract: Old murine bone marrow-derived monocytes and macrophages (BMMs) display enhanced CD38 protein, a nicotinamide adenine dinucleotide (NAD⁺) glycohydrolase, and reduced NAD⁺ level after infection with oral pathogens compared with young controls. We aimed to determine whether treatment with a CD38-specific inhibitor (78c) in mice with experimental periodontitis could alleviate alveolar bone loss and enhance NAD⁺ levels in tissues compared with vehicle treatment. Twenty young (2-month-old) and twenty old (18-month-old) C57BL/6J mice with experimental periodontitis were treated with either vehicle or 78c twice daily via intraperitoneal injection for 4 weeks. The liver, spleen, and right maxillary tissues were harvested to analyze NAD⁺ levels. The left maxillary tissues were scanned by micro-CT, processed for tissue sectioning, and stained with hematoxylin and eosin (H&E) and tartrate-resistant acid phosphatase (TRAP). Treatment with 78c significantly enhanced NAD⁺ levels in the liver and spleen of both young and old mice, and significantly increased NAD⁺ in the right maxilla of old mice compared with vehicle treatment. Additionally, treatment with 78c alleviated alveolar bone loss in both young and old mice. Our results support the notion that 78c is a promising therapeutic strategy for treating periodontal disease associated with aging.