Aging & Longevity

Senescent cells drive ageing and age-related pathologies, including cancer. Consequently, senolytics, drugs that selectively kill senescent cells, have broad therapeutic appeal. Here we report a senolytic screen of a library of 10,480 electrophilic compounds. Among 38 identified hits, we found a subset of chloroacetamides with broad senolytic activity. Activity-based protein profiling, coupled with functional assays, identified the glutathione peroxidase GPX4 as a target. We show that senescent...

A youthful molecular profile reflects attenuated aging and preserved health in advanced age. Long-lived individuals (LLIs) show youthful patterns in DNA methylation and gut microbiota, yet their transcriptional trajectories remain undercharacterized. We analyze transcriptomes from 811 LLIs and 940 younger controls (YCs) to map transcriptional aging trajectories. Clocks trained on YCs reveal that LLIs possess markedly younger transcriptional ages than expected. We identify gene clusters deviating...

CONCLUSIONS: A community-based multicomponent program was linked to sustained IC improvement, mainly through locomotion, while vitality benefits were short-term.

CONCLUSIONS: Dynapenic-metabolic obesity is strongly associated with incident stroke, but even obesity alone increases risk. Systemic inflammation and impaired intrinsic capacity partially mediate these effects, highlighting the importance of integrated strategies targeting adiposity, metabolic health, and muscle function to prevent stroke in aging populations.

Clock-like mutational signatures, principally the single base substitution signatures SBS1 and SBS5, with smaller contributions from SBS18 and SBS40, accumulate approximately linearly with chronological age across nearly all normal human somatic tissues. Initially viewed as simple molecular odometers of lifetime cell divisions, these signatures are now recognised to reflect a far more complex interplay of replication-associated polymerase errors, spontaneous cytosine deamination, oxidative...

Dysfunctional autophagy, a key cellular cleaning process, is a key driver of brain ageing and neurodegenerative diseases such as Alzheimer's disease (AD). However, developing effective treatments by enhancing autophagy has been challenging, as most known compounds act through the broad mTOR pathway, risking side effects, and few can effectively penetrate the brain. To address this, we developed DeepDrugDiscovery-a mechanism-aware, AI-powered screening platform incorporating ADMET and blood-brain...

Although the prevalence of type 2 diabetes (T2D) increases with age, most adults maintain normoglycaemia despite rising insulin resistance owing to the adaptive capacity of pancreatic beta cells to meet increased metabolic demand. However, persistent insulin resistance can lead to beta cell dysfunction and T2D onset. Here we show the mapping of genome-wide DNA methylation (DNAm) patterns and the epigenomic basis of beta cell adaptations by leveraging cell-type-specific methylome data from the...

Age-related skeletal muscle deterioration is a commonly reported disability among older adults, attributed to several factors including mitochondrial dysfunction, a major hallmark of aging. Therapies to attenuate or reverse mitochondrial decline are limited. Despite identified positive relationships between vitamin B12 (B12) and mitochondrial biology, the impact of B12 supplementation on skeletal muscle mitochondria, in advanced age, has not been examined. Thus, the impact of B12 supplementation...

Aging strongly impacts CD8^(+) T cells, including the loss of naive cells and the emergence of age-associated GZMK^(+)CD8^(+) T cells (T(AA) cells). Although T(AA) cells constitute a major population in aged mice, the pathway underlying their differentiation remains unknown. Here, we demonstrate that T(AA) cell development is cell extrinsic and requires antigen exposure within aged non-lymphoid tissues. Using a TNF^(Δ69AU/+) mouse model, we show that low-grade inflammation accelerates CD8^(+) T...

ObjectiveThis study examined whether older adults with informal, professional, or both types of care coordinators (CCs) reported different healthcare quality than those without CCs.MethodsData came from the 2016 Health and Retirement Study (n = 1,555) Module 10 on coordinated care. CC type and the helpfulness of professional CCs were independent variables. Outcomes included perceived confusion about care, conflicting advice from different providers, care satisfaction, and person-centered care....

By 2050, one-fifth of the world is expected to be over 60, and the prevalence of age-related neurological conditions is predicted to increase dramatically. Aged animals are currently underutilised in neurological research, leading to a gap in knowledge about the contribution of biological age to the pathophysiology of age-related neurological conditions. Additionally, it is unclear whether age-related changes differ across species used in preclinical models, and how these differences may compare...

Mitochondrial quality control is essential for maintaining neuronal function and resilience during aging, yet pharmacological strategies that effectively restore mitophagy to maintain mitochondrial homeostasis remain limited. Emerging evidence suggests that dietary molecules may influence mitochondrial health, although the underlying mechanisms are largely unknown. Here, we summarize our recent finding whereby we have identified a robust mitophagy inducer: α-amyrin (αA). This molecule is a...

As global populations age, active aging and lifelong learning have become critical policy objectives. In Taiwan, the Ministry of Education (MOE) promotes Older Adults' Self-Guided Learning Groups (OASLGs); however, the sustainability of these groups relies heavily on volunteer leaders. This study investigates the motivations and management processes of "Excellent Leaders" in OASLGs using a qualitative approach. Drawing on Bronfenbrenner's ecological systems theory, we analyzed semistructured...

GM2 gangliosidoses, including Tay-Sachs (TSD) and Sandhoff (SD) diseases, are lysosomal storage disorders with neurological manifestations caused by the excessive accumulation of GM2 ganglioside due to the deficiency of the β-hexosaminidase A (HexA). Although gene therapy approaches are underway, concerns regarding efficacy and safety remain. Here, we evaluate a tyrosine-mutant adeno-associated virus serotype 9 (AAV9/3) vector encoding modified HEXB (modHEXB) wherein nine amino acid residues are...

Centenarians - individuals aged 100 years or older - constitute a biologically distinct human population that achieves exceptional longevity while frequently retaining functional independence and avoiding major age-related diseases or postponing their onset. Despite their advanced age, many centenarians show relatively preserved immune function and resistance to conditions linked to immunosenescence and chronic low-grade inflammation (inflammageing). These features are especially pronounced in...

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Intratumoral heterogeneity in metastatic cancers complicates effective treatment, as distinct tumor subclones display varying drug sensitivities and metastatic capabilities, interacting through mechanisms that remain poorly understood. In this study, we utilized an isogenic ovarian cancer cell pair distinguished by differential β-catenin signaling: non-metastatic (NM) cells with low β-catenin and highly metastatic (HM) cells with elevated β-catenin signaling. Co-engrafting NM and HM cells...

Advanced glycation end products (AGEs) drive metabolic dysfunction, inflammation, and age-related disease, and their accumulation accelerates after menopause. Preclinical studies show that GLYLO, a five-compound glycation-lowering formulation (alpha-lipoic acid, nicotinamide, pyridoxine, benfotiamine, and piperine), reduces AGE burden and improves metabolic health, but its translational relevance in humans is unknown. The Glycation Reduction and Aging: a Clinical Evaluation (GRACE) trial is a...

Polycystic ovary syndrome (PCOS) and its underlying features remain poorly understood. In this genetic study (n = 544,513), we expand the number of genetic loci from 16 to 29, and additionally identify 31 associated plasma proteins. Many risk-increasing loci were associated with later age at menopause, underscoring the reproductive longevity related to an increased oocyte number and/or availability across the lifespan. Hormonal regulation in the etiology of this condition, through metabolic and...

CONCLUSION: Validity and reliability are established for this ability-based QoL scale, within a sample of mostly cognitively unimpaired, community-dwelling older adults. The QFS-5 aligns with EQ-5D, demonstrating potential clinical and research utility to measure relevant patient-reported QoL outcomes.