Biology and Life Sciences

Abstract: Background/Objectives: Sundowning syndrome—recurrent late-afternoon agitation, disorientation and anxiety in people with dementia—is widely attributed to disturbed light exposure. Existing accounts remain qualitative, specifying neither which property of the ambient light field changes nor when, and so yield no prediction varying with latitude, season or sky conditions. Methods: We combine standard solar geometry, an analytic clear-sky radiance model and measured photoreceptor spectral sensitivities to compute the spectral composition of the light reaching an observer as a continuous function of solar time, at three European latitudes. We track the rod- and cone-weighted components of the sky spectrum and locate their crossover. Results: The short-wavelength content of available light declines steadily through the afternoon, well before nightfall, while the long-wavelength component remains nearly constant. The crossover falls in the late afternoon, at a time set by latitude, geometry and turbidity, within the broad and variably reported onset window of sundowning. Conclusions: We propose that afternoon spectral reddening—rather than darkness itself—is a candidate physical cue for sundowning, possibly mediated by the diminished short-wavelength drive to melanopsin-expressing retinal ganglion cells, whose sensitivity peak lies within the depleted spectral region. The proposal yields testable predictions and implies that lighting interventions should be timed to local solar conditions rather than the clock.

Abstract: Motor dysfunction in the post-stroke sequelae phase (more than 6 months) has traditionally been attributed to structural disruption of the corticospinal tract (Bond et al., 2023). However, the clinically prevalent phenomenon of mismatch between muscle strength and motor function suggests a functional regulatory disorder independent of structural damage. Based on the available literature, this paper proposes the "biomechanical unloading hypothesis"—a mechanism by which eliminating abnormal stress conduction restores the mechanical environment of the central nervous system to its normal physiological range. In the sequelae phase, the fibrotic and adhered investing fascia loses its elastic buffering function (Ley et al., 2025) and generates abnormal shear stress during daily head and neck micromovements; this stress conducts deep through the three-layer collagen network of the deep cervical fascia (Bond et al., 2023; Snosek et al., 2021; Zhang and Lee, 2002), acts on the adventitia of the carotid sheath and its contents (the vagus nerve and cervical sympathetic trunk), and, through mechano-electrical signal transduction mediated by mechanosensitive ion channels such as PIEZO1/2 (Bagriantsev et al., 2014; Xiao, 2024; Rashidi et al., 2025), converts into abnormally enhanced afferent neural signals. These signals upregulate the excitability of GABAergic interneurons in the primary motor cortex (M1) via the nucleus tractus solitarius (NTS)-locus coeruleus (LC) pathway (Bogduk, 2001; Ji and Lee, 2021)—a link supported by multi-level evidence from receptor expression to clinical translation (Papay et al., 2006; Araneda and Firestein, 2006; Hiu et al., 2016; Sawaki et al., 2003; Kim et al., 2014; Okabe et al., 2025)—thereby elevating the discharge threshold of corticospinal tract pyramidal neurons and suppressing residual motor function output. By cutting off the abnormal stress conduction pathway, investing fascia release could theoretically achieve mechanical unloading of the central nervous system, allowing the discharge threshold to return to baseline and motor function to be released. Based on the anatomical distribution of the anterior and posterior circulations (Bond et al., 2023), this paper further deduces the clinical boundaries of this mechanical effect: the extracranial segment of the posterior circulation (vertebral artery V1-V3) is the optimal mechanical response zone (Zhang et al., 2026a; Yuan et al., 2025); the extracranial segment of the anterior circulation (internal carotid artery sheath) is a partial response zone (Bond et al., 2023); and the intracranial segment (thalamus and brainstem nuclei) is a structural damage zone beyond the range of mechanical conduction (Bond et al., 2023). This paper proposes a validation framework and testable quantitative predictions based on shear wave elastography (SWE) (Liao et al., 2023; Dapper et al., 2026; Zandi et al., 2025), transcranial magnetic stimulation (TMS), and diffusion tensor imaging (DTI) (Shakya et al., 2023; Uzun et al., 2024). This hypothesis couples peripheral biomechanical status with central motor cortical excitability regulation, providing an anatomy-oriented, mechanics intervention-centered, testable theoretical framework for secondary rehabilitation in the post-stroke sequelae phase.

Abstract: Centenarians, semi-supercentenarians and supercentenarians (i.e. oldest centenarians) display complex and heterogeneous immune remodelling. In this setting, immune at-trition, memory, cytotoxic defence, inflammatory regulation and tissue surveillance remain sufficiently balanced to support survival with relatively preserved health. This review examines these processes within an integrated framework encompassing sex and gender differences, genetic background, the exposome and immunobiography. We consider how haematopoietic stem cell ageing, age-related myeloid bias, thymic invo-lution, immune ageing and inflammaging contribute to immune-system remodelling across the life course. We then review evidence on immunity in centenarians and in semi- and supercentenarians, including NK cell expansion, T and B cell remodelling and the persistence of long-term immunological memory, as characterised by conventional flow cytometry and, more recently, single-cell transcriptomic analyses. Available data suggest that exceptional longevity does not reflect the maintenance of a youthful immune system, but rather the capacity to accommodate and compensate for age-related immune re-modelling through preserved cytotoxic surveillance, controlled inflammation, main-tained immune memory and favourable lifelong adaptation to antigenic exposures. Understanding these mechanisms may help identify immune trajectories associated with healthspan, delayed morbidity and resistance to age-related diseases.

Abstract: Oxidative stress accumulates early in the central nervous system (CNS) and is one major driver of age-related neurodegeneration. Here we compare major oxidative-stress models, highlighting their distinct mechanisms and disease relevance. We summarize therapeutic strategies ranging from radical scavengers and endogenous antioxidant enhancers to mitochondrial-targeted agents and rejuvenation approaches that restore intrinsic cytoprotective programs. We further discuss emerging oxidative-stress profiling strategies to define individual redox vulnerabilities. Together, mechanistically informed modeling, multidimensional profiling, and targeted restoration of oxidative resilience may enable more precise interventions for age-related CNS degeneration.

Abstract: Alzheimer’s disease (AD) is characterised by progressive accumulation of misfolded proteins and failure of cellular clearance pathways, particularly the autophagy–lysosomal system. Given the limited disease-modifying efficacy of current pharma-cological strategies, intermittent fasting (IF) has emerged as a potentially relevant non-pharmacological intervention capable of modulating energy metabolism, proteo-stasis and cellular stress responses. This review analyses the mechanisms through which IF and fasting-like metabolic states may stimulate macroautophagy and chap-erone-mediated autophagy, and evaluates their potential neuroprotective relevance in AD. Evidence from in vitro models and animal studies suggests that fast-ing-induced metabolic switching, particularly β-hydroxybutyrate production, can modulate AMPK–mTOR signalling, autophagic flux, oxidative stress, synaptic plas-ticity and Aβ/Tau-related proteostasis. However, the translation of these findings to humans remains incomplete. Current clinical studies suggest potential benefits on se-lected cognitive, sleep and metabolic outcomes, but rely mainly on indirect readouts such as neuropsychological testing, peripheral biomarkers, neuroimaging, metabo-lomics and microbiota-derived signatures. Larger, longer and biomarker-integrated randomised controlled trials using nutritionally supervised protocols are required to determine whether IF can safely produce clinically meaningful neuroprotection in AD without increasing frailty, sarcopenia or hypoglycaemic risk in older adults.

Abstract: Aging is an extensive biological process characterized by morphological and functional alterations at different biological scales, resulting in a systematic decline in biological functions ultimately leading to death. Overall, two main types of theories have been proposed: damage-based theories and programmatic theories. We propose a third option, framed in the cognitive perspective on multiscale biological systems. Here, we review the different theories of aging, organize them in a conceptual hierarchy, and integrate our new model within the existing frameworks: aging as a consequence of loss of goal-directedness (in anatomical space). In this model, aging is driven by a dynamical systems-level disruption of homeostatic alignment within cellular collectives that build and repair a healthy body during development and maturation. In this model, morphogenesis is a homeostatic (goal-seeking) process; left with no goals after the developmental phase has been completed, aging can occur in the absence of damage via the functional disbanding of body components from their original aligned goal state. We suggest a roadmap with important implications for regenerative medicine and aging.

Abstract: Periodontitis is a chronic inflammatory disease in which dysregulated host responses to the oral microbial biofilm drive destruction of periodontal connective tissue and alveolar bone. Increasing evidence indicates that chronic periodontal inflammation may reflect not only excessive inflammatory activation but also a failure of active inflammation resolution. Aging may further increase susceptibility to periodontal tissue damage by promoting inflammaging, altering immune cell function, and impairing tissue repair. Among the immune cells involved in periodontal inflammation, macrophages are particularly important because they coordinate inflammatory responses, efferocytosis, tissue remodeling, and restoration of tissue homeostasis. However, how aging alters the resolution-associated functions of periodontal macrophages remains incompletely understood. In this review, we integrate emerging evidence from periodontal disease, aging biology, macrophage immunology, and specialized pro-resolving mediator (SPM) research to propose a framework linking aging-associated macrophage dysfunction to impaired periodontal inflammation resolution and tissue repair. We discuss evidence that aged periodontal tissues exhibit altered inflammatory responses and macrophage-dependent recovery, while SPMs—including resolvins, maresins, protectins, and lipoxins—can promote resolution, regulate macrophage functions, and protect periodontal tissues in experimental models. We further consider how impaired efferocytosis, persistent inflammatory signaling, and altered tissue-remodeling programs may contribute to an age-associated failure of periodontal repair. Importantly, the available literature supports the individual components of this model but has not yet established a complete causal pathway connecting aging, periodontal macrophage resolution dysfunction, and impaired regeneration. We therefore identify macrophage resolution capacity as a potential mechanistic and therapeutic interface between aging and periodontal disease and discuss how SPM-based approaches may provide a strategy to restore inflammatory resolution and promote periodontal tissue repair.

Abstract: Biological stress and aging are traditionally understood primarily through stressor-specific molecular mechanisms, including osmoregulation, stress-signaling pathways, proteostasis impairment, mitochondrial dysfunction, membrane remodeling, and cellular senescence. Despite substantial differences in their initiating mechanisms, diverse stressors and age-related changes are often accompanied by a common functional consequence: a reduced capacity of the cell to reversibly reorganize its intracellular environment and restore a functionally competent state after stressor removal. Here, we propose a unified biophysical theory of aging and stress based on phase plasticity, which considers the capacity of cellular matter to undergo controlled and reversible physical reorganization as a potential integrative level linking molecular mechanisms with functional recovery. The central concept of the model is phase plasticity, defined as the capacity of the cytoplasm, membranes, biomolecular condensates, and intracellular compartments to transition between functionally distinct physical states while retaining the capacity for reversible restoration. On this basis, Phase Rigidity Syndrome (PRS) is introduced as a hypothetical integrative state that may emerge from the progressive and cumulative loss of phase plasticity. We propose that phase rigidity is associated with reduced molecular mobility, altered biomolecular condensate dynamics, impaired membrane fluidity, diminished proteostatic capacity, and delayed or incomplete recovery following stress. Under prolonged or repeated stress, these changes may mutually reinforce one another, promoting a transition from adaptive phase reorganization toward persistent phase rigidity and, under extreme conditions, phase collapse. The theoretical framework integrates the concepts of phase homeostasis, phase buffer, phase resilience, phase recovery, phase memory, phase threshold, and phase-transition window, and introduces a conceptual Phase Resilience Index (PRI) for characterizing the capacity of cells to maintain and restore phase organization. Importantly, PRS is not proposed as an established biological or clinical syndrome, nor is phase plasticity presented as a validated universal variable. Rather, the proposed framework represents a research hypothesis that requires experimental testing. The proposed theory does not replace existing molecular models of cellular stress and aging but introduces an additional biophysical level of integration, at which distinct primary perturbations may partially converge through changes in the capacity of cellular matter to undergo reversible physical reorganization. The scientific value of the framework will ultimately depend on whether measures of phase plasticity provide additional predictive information on cellular resilience and recovery beyond established molecular markers of stress and aging.

Abstract: Chronic low grade inflammation ("inflammaging") is epidemiologically linked to organ specific aging, but tissue resolved proteomic evidence remains limited. In this exploratory study, we used 4D DIA proteomics to profile heart, liver, spleen, and kidney from mice given chronic LPS (0.1 µg/day i.p., 2 months) with or without ibuprofen co treatment (0.02 mg/mL in drinking water). LPS exposure was associated with the most pronounced proteome changes in kidney (488 DEPs) and liver (293), followed by spleen (170) and heart (135). Intersecting LPS associated DEPs with the Aging Atlas database isolated aging annotated proteins; within this subset, ibuprofen co treatment corresponded to opposite direction changes in a tissue dependent manner: kidney (8/13, 61.5%), liver (4/9, 44.4%), spleen (1/8, 12.5%), and heart (0/5). Functional enrichment of these oppositely regulated aging annotated proteins revealed kidney specific enrichment in glucuronosyltransferase and oxidoreductase activities, and liver specific enrichment in iron ion binding and steroid hydroxylase activity. STRING networks showed a kidney specific interaction cluster centered on Jun and Sod2, whereas liver showed only a discrete Egfr–Gstp1 pair. Notably, aging related DEPs functioned as network hubs, directly connecting to approximately 50% of non aging DEPs in liver and 43% in kidney. Collectively, these exploratory findings identify tissue specific proteomic correlates within the aging annotated protein subset—particularly in kidney and liver—generating hypotheses for future validation in larger experimental cohorts.

Abstract: Alzheimer's disease is a disorder of large-scale brain networks, in which pathology propagates along the connectome and degrades it through synaptic and axonal loss. Cognition depends on distributed regions synchronizing their activity, and that synchronization carries a physical cost, set by how many white-matter connections must be engaged, and how strongly, before a network settles into coordinated activity. That cost measures what a damaged network can still coordinate, and not only which connections it has lost. How that cost changes across the disease continuum remains unquantified. Here, we apply QUIET, an edge-centric network-control framework, to the Alzheimer's Disease Neuroimaging Initiative cohort spanning cognitively unimpaired, prodromal, and dementia stages. QUIET integrates the structural controllability of individual white-matter connections with the mutual information between functional timeseries to quantify the control energy required to synchronize a brain network. We found that the QUIET-derived control energy followed an inverted-U along the amyloid--tau axis, rising under early genetic and amyloid risk, peaking at the amyloid-positive, pre-tau stage, and falling as tau accumulated. APOE-\(\epsilon\)4 carriage raised control energy before any detectable pathology, an elevation carried almost entirely by assigned female at birth (AFAB) individuals. Entorhinal tau marked the descending phase, and a large, network-specific hemispheric asymmetry persisted from cognitively normal to Alzheimer's brains. QUIET-derived control energy correlates with the established markers of Alzheimer's disease (cortical amyloid, entorhinal tau, and APOE-\(\epsilon\)4 carriage) in a stage- and sex-dependent manner.

Abstract: Leaf senescence in perennial deciduous trees is a coordinated process linked to seasonal nutrient recycling, crucial for longevity and adaptation. Beyond transcriptional regulation, post-transcriptional mechanisms rapidly fine-tune gene expression and expand transcriptomic diversity. This review synthesizes emerging post-transcriptional regulatory networks governing woody plant leaf senescence. We highlight alternative splicing as a molecular switch, exemplified by PtRD26IR, an anti-aging variant that functions via dominant-negative inhibition of senescence-associated NACs. Additionally, we detail non-coding RNA (ncRNA) networks—including conserved miR164-NAC modules, miR390-tasiRNA-ARF cascades, and lncRNA/circRNA-mediated ceRNA sponging—that integrate hormonal and stress cues. We further explore epitranscriptomic dynamics (m6A, m1A, m5C) regulating mRNA stability and translation in leaf-color variants, along with PPR protein-mediated organellar RNA editing that preserves chloroplast and mitochondrial integrity during decline. Integrating these multi-layered pathways establishes a comprehensive framework for forest longevity and offers precision molecular targets for stress-tolerant, high-yield tree breeding.

Abstract:

Background: Secondary metabolites of lichens have a wide range of biological activity, including geroprotective activity, but their complex effect on the human transcriptome remains poorly understood. The aim of the study was to evaluate the effects of perlatolic acid (PA) and bromoatranorine (Br) on the transcriptomic profile of primary human dermal fibroblasts (HDFs) to identify key target genes and signaling pathways. Methods and Results: HDFs were treated with PA and Br at concentrations of 1µM and 5µM, followed by analysis by high-throughput RNA sequencing (RNA-seq). Using the SenMayo panel, the GeneAge and MatrisomeDB databases, it was shown that PA leads to a significant decrease in the expression of key SASP factors: IL6, CXCL8, CCL2, IL32, and IGFBP family genes. Both compounds led to upregulation of matrix metalloproteinase genes (MMP1, MMP3, MMP12), which, in the case of PA, was accompanied by a predominant suppression of the expression of structural genes of the core matrisome. Based on the Gene Set Enrichment Analysis (GSEA), we identified pathways, such as Cell cycle/replication, genome maintenance, ECM/fibroblast matrix, and RNA/signaling/metabolism, which were significantly modulated by exposure to PA and, to a lesser extent, Br. Conclusions: The study describes for the first time the full-transcriptomic landscape of the response of fibroblasts to lichen depsides. PA acts as an active modulator of genetic networks, stimulating proliferative cascades and remodeling of the matrix. The identified targets open up prospects for the use of PA in regenerative biomedicine, while Br has a limited effect on the transcriptome.

Abstract: Background. The dominant clinical manifestation of aging is not mortality but the progressive depletion of functional reserve—the surplus physiological capacity separating independent function from disability. Existing geroscience frameworks describe the molecular processes of aging in extraordinary detail yet offer the point-of-care clinician little basis for prioritizing targets. Objective. To reframe functional aging as a control-systems problem and to define the minimum set of physiological capacities whose preservation maintains functional reserve. Framework. Aging is modeled as progressive instability within a coupled, bidirectional mitochondrial–epigenetic regulatory axis. Candidate capacities were evaluated against three operational criteria—independence, necessity, and modifiability. Results. Five capacities satisfy these criteria: bioenergetic capacity, endocrine signaling integrity, molecular quality control, adaptive (hormetic) stress response, and neuro-autonomic regulation. Each protects the central axis; together they govern the trajectory of functional reserve. Modifiable interventions are mapped onto these capacities in a separate operational layer. Conclusions. The framework yields a causally ordered, clinically actionable, and falsifiable architecture in which functional reserve is the primary therapeutic target and lifespan a downstream consequence. It is testable against existing longitudinal cohorts without new data collection.

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 lysine 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 remodels the shelterin-dependent telomere-subtelomere chromatin environment, 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: 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: 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.