Aging & Longevity

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...

Mitochondrial DNA (mtDNA) depletion and multiple deletions frequently coexist in mitochondrial disease, neurodegeneration, and aging, yet how the two relate and why deletions accumulate focally remain unresolved. Here, longitudinal bulk and in situ analyses of Mpv17^(-/-) murine muscle reveal that a compensatory rise in mitochondrial transcripts per mtDNA initially offsets severe, uniform mtDNA depletion, preserving the respiratory chain. However, this response carries a delayed cost: by six...

Genome stability depends on the accurate repair of DNA double-strand breaks (DSBs). While chromatin-based mechanisms have been well studied, emerging evidence reveals that nuclear mechanics actively shape repair outcomes, although the mechanisms remain unclear. Here we identify microtubule acetylation as a regulator of nuclear mechanics that promotes DSB repair via homologous recombination (HR). DNA damage induces progressive tubulin acetylation, leading to displacement of the perinuclear...

Aging is accompanied by a progressive decline in tissue regenerative capacity, driven by intrinsic stem cell dysfunction and age-associated deterioration of the surrounding stem cell niche. Mesenchymal stromal cells (MSCs) are ubiquitous components of stem cell niches, where they integrate structural, metabolic, inflammatory, and paracrine cues to regulate stem cell quiescence, activation, and differentiation. With age, MSCs undergo functional decline and senescence, altering their secretory and...

Aging is associated with progressive oxidative stress, chronic inflammation and functional deterioration across multiple organs. Increasing evidence suggests that the gut microbiota plays a pivotal role in regulating aging through the gut-brain axis and systemic immune interactions. The present study investigated the therapeutic potential of fecal microbiota transplantation (FMT) in a D-galactose-induced rat model of accelerated aging. Male rats were allocated into four experimental groups:...

Oxidative stress is a hallmark of aging and a key driver of neurodegenerative diseases. While much attention has been given to oxidative damage of macromolecules, the functional consequences of oxidizing the abundant nucleotide triphosphate (NTP) pool remain largely unknown. Here, we identify oxidized GTP (8-oxoGTP)-a major product of NTP oxidation-not as a mere marker of damage, but as an endogenous signaling molecule that drives microglial activation and neuroinflammation. 8-oxoGTP accumulated...

Chemotherapy-induced cognitive impairment (CICI), often referred to as "chemobrain," is a frequently persistent complication that significantly affects memory, attention, executive function, and overall quality of life among cancer survivors. Although mitochondrial dysfunction, oxidative stress, neuroinflammation, and gut microbiota dysbiosis have each been implicated in its pathogenesis, the way these processes interact to drive cognitive decline remains incompletely understood. In this...

The condition of having a healthy, functional proteome is known as protein homeostasis, or proteostasis. Establishing and maintaining proteostasis is the province of the proteostasis network, a highly interconnected system of over 3000 components that regulate protein synthesis, folding, localization, and degradation. The proteostasis network is a fundamental functional unit in biology that is essential for cellular health and has direct relevance to many diseases of protein conformation....

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CONCLUSION: This study demonstrates that digital engagement is significantly and positively associated with SPA among older adults, with Internet use skills serving as an important moderating factor. Three interventions are needed: age-friendly interfaces, targeted engagement strategies, and digital literacy programs. Bridging the digital divide is essential for positive aging.

CONCLUSIONS: Combining dual-task gait variability with clinical functional assessments via machine learning algorithms provides a robust and interpretable framework for faller identification. The integration of optical gait analysis and machine learning facilitates early risk screening and personalized retrospective evaluation, offering a promising tool to assist in detecting older adults at risk for fall-related injuries in the aging population.

CONCLUSIONS: Findings suggest that hs-CRP and CRP biomarkers are associated with physical performance decline in older adults. Future research including a broader range of inflammation biomarkers should provide insights and understanding of mechanisms linking inflammation and physical decline.