Aging & Longevity

The accumulation of advanced glycation end products (AGEs) in long-lived proteins is a hallmark of mammalian aging and implicated as a driver of metabolic dysfunction. Among these adducts, N^(ε)-carboxymethyl-lysine (CML) is particularly abundant in aging tissues, where it modifies proteins and acts as a ligand for the receptor for advanced glycation end products (RAGE), thereby perpetuating chronic inflammation and oxidative stress. While endogenous detoxification systems exist for reactive...

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Understanding the consequences of individual DNA methylation variation is crucial for advancing our knowledge of human biology and disease. Yet, the collective impact of individual traits on DNA methylation and their downstream effects on gene expression across human tissues remain poorly understood. Here, we quantify the contributions of sex, age, genetic ancestry, and BMI on autosomal DNA methylation variation across 9 human tissues and 424 individuals from the Genotype-Tissue Expression...

A significant subset of tumors, including >50% of osteosarcomas-an aggressive bone malignancy affecting children, adolescents, and young adults-relies on alternative lengthening of telomeres (ALT), a telomerase-independent, DNA repair-based mechanism for telomere elongation. The overall 5 year survival rate for osteosarcoma patients is ∼65%, underscoring the need to develop novel targeted therapies. Through the Cancer Dependency Map, we identified SMARCAL1, a DNA translocase previously shown to...

This study applied Ward's hierarchical clustering to detailed neuropsychological data from a community-recruited sample of 180 older adults to identify naturally occurring cognitive subgroups and characterize multidomain cognitive heterogeneity beyond conventional mild cognitive impairment (MCI) criteria. Twenty-two demographically adjusted z-scores spanning memory, language, executive function, and attention/processing speed were submitted to Ward's method, and the resulting four-cluster...

Loss of muscle mass and quality (myopenia and myosteatosis) are hallmarks of aging and predictors of disability, yet their relationship with biological aging in younger adults is unclear. This prospective cohort study included 165,015 adults (mean age 39.9) who underwent low-dose chest computed tomography (CT) between 2010 and 2020. A longitudinal subset of 61,669 participants had repeated scans (median follow-up 4.1 years). We adopted blood-based Phenotypic Age acceleration (PhenoAgeAccel) and...

Introduction Falls are a major public health concern among older adults, leading to injuries, loss of independence, and increased mortality. A Body Shape Index (ABSI), which integrates waist circumference with height and weight, may better capture abdominal adiposity than BMI. To our knowledge, this is the first study to examine the association between ABSI and fall risk in older adults using data from the National Health and Aging Trends Study (NHATS). Methods We analyzed data from NHATS, a...

CONCLUSIONS AND IMPLICATIONS: Social prefrailty and frailty are prevalent and follow a clear educational gradient. Integrating social frailty assessments into routine clinical screenings and directing targeted policy interventions toward less-educated older adults are urgently needed to promote healthy aging.

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.