Aging & Longevity

Exercise is a powerful non-pharmacological strategy for preserving brain health during aging. However, whether intrinsic exercise capacity is associated with a distinct molecular phenotype in the aged brain, independent of training intervention, remains unclear. Aged selectively bred low-capacity runner (LCR) and high-capacity runner (HCR) rats were studied. Hippocampal DNA methylation was profiled by reduced representation bisulfite sequencing (RRBS), and differentially methylated regions...

The buildup of toxic aggregates formed by the amyloid-β peptide 1-42 (Aβ(42)) is a central process in Alzheimer's disease (AD) pathology. The peptide's self-assembly and toxicity are highly dependent on its primary amino acid sequence and can be altered by modifying key residues. Specifically, the single amino acid substitutions A30W, K28A, and M35C can reduce the aggregation and toxicity of the Aβ(42) peptide. In this study, we further evaluated the effects of these mutations in a C6 rat glioma...

Male reproductive ageing is a complex process involving progressive and detrimental histological and physiological alterations to the testis and beyond. Age-related morbidities often confound reproductive function, making it difficult to disentangle systemic from reproductive male ageing. We have previously shown that healthy ageing is associated with full spermatogenesis, normal sperm production and hormonal secretion. However, the molecular mechanisms allowing the human testis to age without...

Age-associated thymic involution leads to a reduction of T-cell production, which constitutes a primary factor in immunosenescence, thereby increasing vulnerability to cancer, infections, and autoimmune disorders. Thymic epithelial cells (TECs), essential for T-cell development, exhibit progressive senescence with aging. The development of strategies to mitigate TECs senescence and delay thymic degeneration has emerged as a significant research focus. Here, aged C57BL/6J mice and immortalized...

Aging is accompanied by both increasing interindividual heterogeneity and systematic, age-associated alterations in DNA methylation (DNAm). Here, we investigated these complementary dimensions of epigenetic aging in dogs using global and locus-specific measures of epigenetic drift alongside clock-based estimates of biological aging. We observed pervasive, yet genomically structured epigenetic instability throughout the canine lifespan. The extent of age-associated epigenetic drift further varied...

Cytosolic DNA and RNA sensing is crucial for innate immunity, playing essential roles in pathogen defense and autoinflammation induction. We reported the endogenous metabolite flavin adenine dinucleotide (FAD) as a molecular brake restraining both cytosolic DNA and RNA sensing. It bound directly to cytosolic nucleic acid sensors cyclic GMP-AMP synthase (cGAS) and retinoic acid-inducible gene I (RIG-I), occupying catalytic pockets to suppress their activity and downstream immune responses....

BACKGROUND: Latin America faces a high dementia burden, with increased prevalence of factors associated with cognitive decline. Multidomain lifestyle interventions might delay cognitive decline, but populations from Latin America remain under-represented in dementia prevention trials. We aimed to investigate the feasibility of a culturally adapted, multidomain, systematic lifestyle intervention and investigate its effects on global cognitive function in at-risk older adults (aged 60-77 years).

Vascular aging contributes to systemic dysfunction and underlies many age-related diseases, driven by structural and functional changes across various cell types, including endothelial cells, vascular smooth muscle cells, pericytes, and cardiomyocytes. This review highlights experimental models that facilitate mechanistic insights and the development of novel therapeutic approaches for vascular aging, emphasizing both in vitro and in vivo methodologies. This review discusses in vitro models...

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Sustained attention is a core cognitive function, frequently declines with age and neurological disease, and is highly relevant for functional outcomes in geriatric populations. Electroencephalography (EEG) offers high temporal resolution for assessing attentional processes, but its feasibility in multimorbid geriatric inpatients remains insufficiently characterized. This study evaluated the procedural and methodological feasibility of EEG-based sustained-attention assessments in geriatric...

Aging is often framed as the gradual erosion of proteostasis, driven by declining chaperone capacity, impaired degradation, and dysregulated protein synthesis. Yet this view implicitly assumes that proteins fail primarily because they misfold or escape clearance. Increasing evidence instead points to a more fundamental problem: aging disrupts the spatial management of the proteome. Gradually, proteins are misplaced, signaling pathways are uncoupled from their compartments, and condensates that...

CONCLUSIONS: Findings underscore the importance of emotionally engaging and expectation-aligned services in mitigating social isolation, with extended services generating the most durable benefits. Strengthening HCBS to address psychosocial and physical needs may support aging-in-place and inform responsive community-based care systems in China and beyond.

With an ageing population and the persistence of unhealthy lifestyle behaviours, health-care systems are challenged by a growing number of individuals living longer with cardiovascular disease and its sequelae. The evolution of cardiac rehabilitation, from a group exercise-based programme to encompassing all aspects of secondary prevention, has led to the ultimate objective of achieving lifelong cardiovascular health for all. In this World Heart Federation Roadmap, we present a united and...

Brain white matter undergoes structural and functional alterations linked to late-life cognitive decline, but the cellular and molecular basis of its selective vulnerability remains incompletely defined. Here, in naturally aged mice, we demonstrate that senescent and disease-associated microglia (DAM) phenotypes converge in hippocampal-adjacent white matter, particularly in the fimbria. Using regional gene expression profiling, immunolabeling, GeoMx digital spatial profiling and CosMx spatial...

Chronic pruritus (or itch) is a common condition associated with aging; however, the neural mechanisms driving age-related itch hypersensitivity remain largely unknown. Here, we investigated the role of serotonergic signaling in modulating itch sensitivity during aging. Aged mice exhibited enhanced mechanical alloknesis without changes in spontaneous scratching behavior, indicating that aging selectively affects mechanically evoked itch. Consistent with this phenotype, aged mice showed elevated...

CONCLUSIONS: The findings contribute to the identification of groups most vulnerable to low social support and low social participation among older adults with disabilities. Because these patterns vary according to the type of social support and type of participation, this study highlights the importance of targeted strategies to promote social inclusion in aging populations.

Accelerated cellular perturbations such as cellular senescence, neuroinflammation and oxidative stress are hallmarks of Alzheimer's disease, a neurodegenerative disease associated with memory decline. However, the senolytic effects of silymarin, a flavonolignan with known antioxidant and anti-inflammatory properties, on memory decline remain unknown. Hence, we investigated the effect of silymarin on doxycycline-mediated senescence and exacerbated neuroinflammation in lipopolysaccharide-induced...

Biological ageing is a heterogeneous process that shapes susceptibility to chronic disease. However, whether ageing patterns diverge within clinically defined type 2 diabetes (T2D) subgroups remains unclear. We investigated whether epigenetic age acceleration (EAA) differs across T2D phenotypes and whether these patterns relate to subsequent renal vulnerability. We included 607 multi-ethnic Asians with recent-onset T2D previously classified into three clinically distinct subgroups: mild...

Age-related subcutaneous adipose tissue (SAT) atrophy is a hallmark of aging, contributing to metabolic dysfunction and systemic aging. The mechanisms underlying SAT atrophy and potential therapeutic strategies remain poorly understood. Here, we report that small intestinal epithelium-derived exosomes (SI-Exos) mediate gut-adipose communication and play a pivotal role in age-related SAT remodeling. We found that the miRNA cargo of SI-Exos undergoes significant age-related changes. Administration...

OBJECTIVES: Evidence on the association between work and cognitive ageing has been mixed, and research from China remains limited, particularly with respect to heterogeneity in cognitive function trajectories. This study examined whether paid work participation in later life is associated with distinct cognitive function trajectories among older Chinese adults.