Aging & Longevity

CONCLUSION: Nicotine attenuated selected D-galactose-associated behavioral and hippocampal alterations. The genotype comparisons support α7-nAChR-associated modulation of platform-site crossings, serum GSH, and hippocampal IBA1. They do not establish that changes in brain GSH or amyloid production mediate these effects, or that all nicotine responses share one receptor-dependent mechanism.

Age-related declines in pulmonary function and immune regulation increase morbidity and mortality in older adults. Physical activity mitigates these effects, but the isolated impact of resistance training (RT) on lung function and immune responses remains unclear. Sixty-nine older adults without participation for at least one year in structured exercise programs (aged 60-85 years) were recruited from a community extension program at a Brazilian university and randomized into an RT group (n = 31)...

CONCLUSIONS: Older adults with higher mortality risk had poorer social wellbeing at baseline and were more likely to become lonely and decrease social participation at follow-up. Prognostic information may help clinicians avoid low-value medical interventions while prioritizing interventions to support meaningful social connection.

ObjectiveTo examine the association between early-life circumstances and healthy aging among community-dwelling older Chinese adults.MethodsData were from the China Health and Retirement Longitudinal Study. We used regression methods to identify independent and joint associations of six early-life factors with healthy aging as assessed by the Chinese Healthy Aging Index (CHAI; 0-12), a composite score evaluating six physiological systems.ResultsOf 3,069 participants, 4.82% had the healthiest...

ObjectivesUsing longitudinal data, we investigate changes in coresidence preference of Chinese older adults and, with application of the Andersen-Newman framework, examine factors contributing to coresidence preference.MethodsData come from five waves of the Chinese Longitudinal Healthy Longevity Survey collected between 2005 and 2018. A random-effect model uses baseline covariates to predict coresidence preference at follow-up between two adjacent waves, controlling for baseline preference and...

There is an urgent global need for affordable, large-scale health screening to enhance preventive care in the ageing population. Using low-cost, non-invasive retinal photographs and leveraging large foundation models, we developed a deep learning-based biomarker, Retinal Mortality Equivalent (RetiME), that directly mapped retinal features to individual mortality risk. Trained on a European cohort and externally validated across three independent external cohorts spanning Southeast Asia, Eurasia...

Assessing and validating circulating biomarkers is essential for developing preclinical measures of biological aging in mice. However, comprehensive serum proteomics are limited by technical challenges and low sample volumes. Here we present a quantitative nanoparticle-based enrichment workflow coupled with data-independent acquisition mass spectrometry for deep proteomic profiling of low-volume mouse serum. This approach increased proteomic coverage by 3-6-fold with median coefficient of...

Iron accumulation is a conserved hallmark of cellular as well as organismal aging, yet its mechanistic role in senescence remains largely elusive. Here we show that the accumulation of ferrous iron (Fe^(2+)) in lysosomes, a unique feature of senescent cells, is crucial for the induction of multiple senescence-associated phenotypes. Intriguingly, we found that this lysosomal Fe^(2+) sequestration is rendered "safe" by a dual metabolic adaptation that confers robust resistance to ferroptosis....

Reproductive aging impairs female fertility, and oocyte aging is considered a major driver of this phenotype, which manifests with increased aneuploidy and miscarriage risk, while no effective treatments have been widely implemented to date. Here, we report comprehensive protein expression profiling of oocytes during human aging, comparing fully grown germinal vesicle oocytes (FGO) and metaphase II (MII) oocytes; we describe the effect of aging on the maturation profiles across multiple age...

CONCLUSION: The Korean short-form AARC is better interpreted as a subscale-based measure than as a single total score. Further validation and refinement are needed, particularly regarding selected item wording, item coverage, response category functioning, and subgroup comparability, before the scale is used for precise individual-level assessment.

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...