Aging & Longevity

Aberrant activation of the STING signaling pathway is involved with aging-related inflammation, yet no STING-targeting therapeutics are clinically approved. Here, we identify Omaveloxolone, an FDA-approved drug for Friedreich's ataxia, as a potent STING degrader (DC(50) = 118 nM, D(max) = 98.6%) via high-throughput screening. Omaveloxolone binds non-covalently to the base of the STING ligand-binding domain (LBD) with high affinity (K(D) = 21.4 nM) and exhibits crowbar-like behavior consistent...

During mitotic growth, Saccharomyces cerevisiae cells age by dividing asymmetrically, producing young daughter cells while retaining age-associated damage in the mother cell, which will eventually become senescent. Gametogenesis naturally and fully resets precursor cell lifespan, even for replicatively aged cells. However, the mechanisms responsible for gametogenic rejuvenation have remained mysterious. This is partly due to the existing methods to quantify lifespan resetting in this context,...

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In mammals, oocytes initiate meiosis during fetal development and then enter a prolonged meiotic arrest. During this female-specific long-term arrest, chromosome cohesion mediated by nonrenewable REC8 cohesin gradually deteriorates, predisposing oocytes to age-associated chromosome segregation errors when meiosis resumes for maturation in adulthood. Female-specific factors that counteract this deterioration remain unknown. Here we identify OMC1 as an oocyte-specific chromosomal protein required...

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CONCLUSION: Cognitive frailty is independently associated with a significantly increases elevated risk of hip fractures in older Chinese older adults, highlighting it as a clinically important and modifiable risk factor. These findings underscore the need for integrated screening protocols that simultaneously assess both cognitive and physical frailty in geriatric care settings.

CONCLUSION: This external pilot showed no superiority of CO-OP plus creative dance over CO-OP alone for the prespecified primary outcome (executive function). Preliminary signals for global cognition and dual-task accuracy warrant confirmation in an adequately powered definitive trial with a prespecified, clinically meaningful primary endpoint.

CONCLUSION: Approximately one-third of older adults had problematic-limited / inadequate health literacy. An independent association was observed between limited HL and a higher probability of being physically inactive. However, health literacy was not independently related to smoking. These findings imply that health literacy may be an important factor underlying differences in physical activity engagement among older adults. Community-based strategies integrating health literacy support and...

CONCLUSIONS: We found that although living alone is associated with mortality, adjustment for social and functional factors may attenuate this association. However, specific subgroups with low income, and scarce social relation lead to increased CCV mortality. Further study with a larger sample size is necessary to confirm this finding.

CONCLUSIONS: This multi-cohort integrative study defines the cellular and clonal signatures of latent CMV in humans and identifies GZMK⁺ CD8⁺ T cells and Th1 cells as previously underappreciated components of the CMV response.

CONCLUSIONS: The findings suggest that healthy ageing in this sample was characterized by multidimensional, heterogeneous and interrelated profiles rather than residential status alone. Functional movement quality and environmental engagement were associated with several healthy ageing indicators, but causal mechanisms cannot be inferred. The results should be interpreted as exploratory and hypothesis-generating, warranting confirmation in larger longitudinal and intervention studies.

In this issue of Cell, Grońska-Pęski et al. examine how calorie restriction (CR) affects DNA mutation rates. While CR lowers the accumulation of mutations, this effect does not scale with the degree of lifespan extension. Their work raises important new questions about how CR impacts the causal mechanisms of aging.

Autocrine signaling through vascular endothelial growth factor receptor-1 (VEGFR-1) reprograms T cell metabolism upon TCR stimulation. We found that mice bearing conditional deletion of Flt1 (encoding VEGFR-1) in T cells developed spontaneous obesity with advancing age. Analyses of lymphoid and metabolic tissues identified a VEGFR-1^(+) T follicular helper (Tfh) population in Peyer's patches and mesenteric lymph nodes. Flt1 deletion impaired Tfh fitness and reduced secretory IgA in the gut,...

Mitochondria arose from an alphaproteobacterial endosymbiont that became integrated within an archaeal host during eukaryogenesis. The discovery of Asgard archaea has clarified host ancestry and supports reconstructions in which aspects of cytoskeletal and membrane complexity preceded mitochondrial acquisition. Organellogenesis involved genome reduction, gene transfer, protein import, metabolic coupling, and vertical inheritance. These evolutionary principles complement current mitochondrial...

Parental age influences offspring traits across species, yet the molecular pathways by which maternal state modulates progeny neural function remain poorly defined. Here we demonstrate that maternal age in Caenorhabditis elegans regulates progeny avoidance of the social pheromone by modulating the activity of a defined sensory circuit. Progeny of young mothers exhibit stronger activity of the pheromone-sensing ADL neurons and enhanced pheromone avoidance, whereas progeny of older mothers display...

[This corrects the article DOI: 10.3389/fnagi.2026.1929453.].

The corneal nerve plexus is essential to ocular surface homeostasis through sensory detection, trophic support, epithelial repair, blinking, and lacrimal reflexes. In dry eye disease (DED), chronic hyperosmolar, inflammatory, mechanical, and age-related stressors alter nerve morphology and function, contributing to reduced nerve density, aberrant regeneration, microneuroma formation, sensory loss, and peripheral or central sensitization. This review summarizes the ultrastructure of corneal...

Biological age estimation is increasingly used in aging research, but evaluation often relies too heavily on mean absolute error (MAE) against chronological age. We conducted a narrative review of major molecular aging clocks and propose an operational framework that links clock selection to the intended task. Applications are organized into four tasks: chronological-age estimation, age-independent deviation, future disease or mortality risk, and longitudinal monitoring of aging pace or...

Chronic low-grade inflammation ("inflammaging") drives age-related decline, but whether anti-inflammatory medications preserve functional performance in older age remains unknown. This study evaluated the 5-year effect of aspirin on a modified Intrinsic Capacity (IC) index in older males and females. A post-hoc analysis of a randomised controlled trial comparing daily 100 mg aspirin to placebo in prolonging dementia- and disability-free survival (DFS) in community-dwelling individuals aged ≥ 65...

The locus coeruleus (LC) brainstem cell group is evolutionarily conserved across vertebrates and influences both mind (cognition) and body (cardiorespiratory, metabolic, and immune functions) via two-putatively distinct-spontaneous activity patterns. Yet, the degree to which spontaneous LC firing rates and patterns are homogeneous across species has never been assessed due to inherently limited sample sizes. To remedy this, we pooled cross-species data from 20 laboratories to show that firing...