Aging & Longevity

When subject to damage or stress, cells develop responses in order to maintain tissue homeostasis. Two such responses are ferroptosis and cellular senescence, but how cells decide between these outcomes remains unclear. Here, we show that senescent cells increase import and membrane levels of multiple polyunsaturated fatty acids (PUFAs), but a specific intermediate PUFA, dihomo-gamma-linolenic acid (DGLA, 20:3ω-6), is reduced. Exogenous repletion of DGLA instead results in cell death by...

The major characteristics of cellular senescence are stable cell-cycle arrest, accumulation of DNA damage responses, mitochondrial dysfunction, metabolic remodeling, and the release of pro-inflammatory senescence-associated secretory phenotype (SASP) factors. Redox imbalance plays a significant role in the initiation and maintenance of senescence, and the mammalian thioredoxin system-comprising cytosolic Trx-1, mitochondrial Trx-2, thioredoxin reductases (TrxR1, TrxR2), and the inhibitor...

Chromatin stability and nuclear architectural integrity constitute the primary defense against cellular senescence. Their collapse precipitates genomic disarray, epigenetic misregulation, and functional decline in stem cells. Although TOP2A is conventionally known for resolving DNA topological stress, its role in aging remains largely unexplored. Here, we found that TOP2A expression progressively decreased in senescent mesenchymal stem cells (MSCs), and its depletion initiated a catastrophic...

Epigallocatechin gallate (EGCG), a major tea polyphenol, has been proposed to promote healthy aging, but population-level evidence and underlying mechanisms remain unclear. We analyzed 10,977 participants from the National Health and Nutrition Examination Survey (NHANES) and conducted mechanistic studies in Caenorhabditis elegans and AML12 hepatocytes. Compared with non-consumers, both lower and higher EGCG intake categories were associated with lower PhenoAge acceleration, lower all-cause...

We developed a machine learning framework grounded in a computational model of brain function and FDG-PET imaging to predict Alzheimer's disease (AD)-type tau across AD and related disorders (ADRD). The model was trained on 1088 research participants spanning normal aging and ADRD with FDG-PET and flortaucipir-PET (FTP-PET). Validation was conducted in: (1) a longitudinal subset of the training cohort (n = 215), (2) Alzheimer's Disease Neuroimaging Initiative (n = 295), and (3) a heretogeneous...

Adaptive modulation of physiological traits in response to dietary fluctuations is essential for organismal fitness and is governed by complex gene-diet interactions that remain mechanistically unexplored. Here, we identify the conserved mTORC2 component RICTOR as a critical regulator of dietary plasticity in Caenorhabditis elegans. Loss of rict-1/RICTOR confers enhanced osmotic stress tolerance and longevity on vitamin B12-rich bacterial diets containing optimal methionine. These adaptations...

Ageing-associated inflammation ("inflammaging") is characterised by chronic microglial priming or overactivity that elevates neurodegeneration risk. Microglia also accumulate autofluorescent lipofuscin as they age-aggregates of oxidised lipids, misfolded proteins and metals that generate reactive oxygen species. Characterising age-related changes in brain autofluorescence could provide insight into brain ageing dynamics and could identify associations with potential biomarkers in accessible...

Efforts to extend longevity and healthspan have benefited from the use of in vitro systems, short-lived model organisms and computational approaches, but translation to humans depends on demonstrating efficacy and safety in mammalian in vivo models. However, rigorously controlled rodent lifespan studies are slow, costly and low-throughput. Hormesis, the induction of adaptive stress response pathways by low-level toxic or metabolic challenges, provides a mechanistic means for improved resilience,...

Biological aging drives cellular dysfunction and human disease, yet studying human aging dynamics remains challenging due to limited experimental platforms. Here we show that long-term post-mitotic culture of human fibroblasts recapitulates and accelerates features of in vivo aging. Longitudinal paired transcriptomic and epigenetic analyses of four female fibroblast lines revealed that in vitro aging reflects key signatures of in vivo primary fibroblast aging. Direct neuronal conversion of in...

Gene transcription by RNA Polymerase II (Pol II) is highly vulnerable to transcription-blocking DNA lesions (TBLs), which, if unresolved, induce transcription stress leading to cellular decline and aging. TBLs are removed by transcription-coupled nucleotide excision repair (TC-NER). TC-NER is initiated when Cockayne syndrome group B protein recognizes lesion-stalled Pol II and promotes TC-NER complex assembly. This complex recruits TFIIH for lesion verification, followed by incision and repair...

As they age, older adults are increasingly susceptible to health decline associated with excessive alcohol consumption, which can accelerate biological aging through cellular stress, senescence-associated responses, and inflammaging. Although sesaminol, a sesame-derived lignan, protects against alcohol-induced colitis in young animals, its effects on alcohol-associated intestinal dysfunction and senescence-related changes in middle-aged animals remain unclear. In this study, middle-aged mice (50...

Circadian biology is recognized for its importance to physiology and metabolism, with implications for healthy aging and disease risk. To test whether altering the number of imposed environmental cycles experienced per unit chronological time affects health biomarkers and lifespan, we compressed and expanded the photic cycle (T-cycle, combined light:dark length) by ~ 10% relative to the 24-h day. Male C57BL/6 J mice (n = 60 per group, 12 weeks old) were randomized to one of three T-cycles: T ~...

Aging is a universal biological process signified by a time-dependent decline in physiological activity, driven by molecular and cellular damage, leading to greater susceptibility to diseases and fatal outcomes. Impaired proteostasis is a key aspect of cellular aging in which the cells become less efficient at folding, repairing, and recycling proteins, consequently inducing accumulation of damaged and aggregation-prone proteins. The onset of muscle loss is driven by a reduction in protein...

Quantifying biological aging and predicting age-related functional decline are increasingly important for reducing the health and socioeconomic burden of population aging. DNA methylation is one of the most extensively studied epigenetic features of aging and underlies epigenetic clocks, promising quantitative biomarkers of biological age. However, the molecular processes driving age-associated DNA methylation changes and the biological signals captured by these clocks remain unclear. A major...

Radiotherapy combined with immunotherapy has emerged as a promising therapeutic strategy across multiple cancer types. However, despite encouraging findings from selected clinical trials, most radioimmunotherapy studies have shown only limited or even negative results, highlighting important biological barriers that limit therapeutic efficacy. Accumulating evidence suggests that radiotherapy induces phenotypic and functional changes in immune cells that resemble key features of age-related...

Bone marrow macrophages (BMMs) coordinate skeletal remodelling, haematopoietic niche function, immune surveillance, and tissue repair. Whether a persistent senescent state in BMMs is a causal driver of skeletal ageing, however, remains unresolved. The central challenge is both definitional and causal: macrophages may be quiescent, terminally differentiated, chronically activated, tolerant, or metabolically dysfunctional, whereas commonly used senescence markers-including p16^(INK4a), p21^(CIP1),...

DNA-protein crosslinks (DPCs) are one of the most complex and deleterious forms of DNA damage. DPCs arise from the stabilization of covalent enzyme-DNA intermediates, such as topoisomerase cleavage complexes, or from exposure to bifunctional crosslinking agents, and they differ in protein identity, DNA context and chemical linkage. Because of their bulky nature, DPCs obstruct essential chromatin processes such as DNA replication and transcription, making their timely removal by dedicated DPC...

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Terrestrial ecosystems are changing rapidly under global nutrient enrichment, yet how canopy nutrients balance shapes the seasonal end of photosynthesis, a critical control on ecosystem carbon cycling, remains unclear. Rising anthropogenic nitrogen inputs are shifting many ecosystems towards relative phosphorus limitation, with uncertain consequences for autumn phenology. Here, we combined airborne imaging spectroscopy with remotely sensed phenology to test whether canopy nutrient ratios predict...

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and is promoted by atrial fibrosis, a form of structural remodelling for which effective therapies are lacking. MicroRNA-31-5p (miR-31-5p), an aging-associated, atrial-enriched microRNA, has been linked to AF, but its role in atrial fibrosis is unknown. Here we show that atrial fibroblasts from patients with persistent AF exhibit increased miR-31-5p expression and reduced expression of the calcitonin receptor (CTR, encoded...