Aging & Longevity

No abstract

Telomere capping largely depends on telomere length. Abnormally short telomeres are prone to activate DNA damage checkpoint, undergo unscheduled chromosomal fusions through nonhomologous end-joining (NHEJ) and be resected. All these processes are mediated by the Mre11-Rad50-Xrs2^(NBS1) (MRX^(MRN)) complex. The response to telomere length is thought to correlate with the number of DNA-bound telomeric proteins but the mechanisms translating this number into functional protection remain unclear....

Recent work leveraging omics and imaging data now enables the estimation of aging at the level of individual organs. Emerging findings suggest that organs age at different rates, which may be linked to environmental exposures and genetic factors. However, premature aging in one organ may also drive aging in connected organs within multi-organ aging networks. Here, we outline methods for measuring organ-specific biological age and discuss insights derived from recent progress in multi-organ aging...

Biological age may provide a more informative metric of individual physiological function and life expectancy, compared to chronological age. Proteomic aging clocks are predictive models trained using high-dimensional proteomic data to quantify biological age. Owing to the central biological role of proteins and their established clinical utility as druggable targets and prognostic biomarkers, proteomics is particularly promising for the assessment of aging. In this Review, we provide an...

Aging impairs coordinated organelle dynamics essential for lipid metabolism, causing a decline in intracellular metabolic flexibility. However, the drivers of organelle collapse and their temporal order remain unclear. Here we identify peroxisomal function as a critical regulator of metabolic flexibility during youth and low-energy states. Using Caenorhabditis elegans, we show that fasting robustly induces peroxisomal function in youth, whereas this response is blunted during aging. Loss of...

Intrinsic capacity (IC) is a crucial determinant of healthy aging, operationalized through five essential functional domains -- locomotion, cognition, vitality, psychological, and sensory capacities. Integrating geroscience principles with IC assessment in preclinical models with accelerated aging profiles can support bidirectional translation. This narrative review aimed to summarize measurement approaches for each IC domain and to show how IC evolves longitudinally in mouse and fish models. A...

CONCLUSIONS: Observational analyses link diabetes and prediabetes to poorer balance performance, and genetic evidence supports an association between diabetes liability and increased fall risk.

Host-associated microbiomes are compositionally stable across most of the life span, yet undergo consistent and marked deterioration during aging, a phenomenon linked to metabolic dysfunction and disease. What drives this late-life collapse remains poorly understood, in part because the mechanisms by which hosts actively construct and maintain the microbial niche during adulthood remain incompletely characterized. This Unsolved Mystery integrates evidence from immunology and ecosystem ecology to...

The menstrual cycle is a rich yet underused source of physiological information. To address this, we developed an open-source tool called WAVES (women's health assessment through variability in endocrine-related signals) that leverages physiological signals to extract menstrual cycle metrics and facilitate biomarker discovery. We tested it on basal body temperature data from 5674 nonconceptive cycles from 753 participants aged 18 to 42 years. We identified multiple associations between aging and...

Age-related cataract (ARC) is a severe vision-impairing disorder primarily caused by oxidative stress-induced senescence and apoptosis of lens epithelial cells (LECs). In this study, a sodium selenite-induced oxidative stress cataract model in neonatal rats was established to simulate the pathological progression of ARC. We found that retinoic acid receptor-related orphan receptor α (RORA) exacerbates cellular senescence and oxidative damage by targeting prion protein (PRNP), and its...

Methionine restriction (MR) extends the lifespan and healthspan of numerous eukaryotic organisms, but the molecular mechanisms at play are unclear. Here we find that the ability of MR to extend the budding yeast chronological and replicative lifespans is the consequence of reduced methionine conversion to the methyl donor S-adenosylmethionine (SAM). Mechanistically, the key antiaging event downregulated by MR is the methylation of protein phosphatase 2A (PP2A). In chronological aging cells under...

CONCLUSION: It was found that nursing interventions in the observational group, compared to the control group, significantly improved satisfaction rates and alleviate complication rates. These findings suggest that various nursing intervention programs can effectively enhance rehabilitation outcomes in older patients following fractures.

CONCLUSIONS: The total IC score and components of each domain were associated with the risk of falls and functional decline after 5 years.

CONCLUSION: Community based intergenerational project offer a promising approach to address social isolation and promote well-being in elderly individuals while also enhancing intergenerational connections and community resilience.

Intracerebral hemorrhage (ICH) is a neurological disorder characterized by a high mortality rate for which there is currently no definitive cure. Research has demonstrated that adipose-derived mesenchymal stem cells (ASCs) exhibit considerable potential in treating ICH. However, the advanced age of ICH patients and the necessary cell expansion before transplantation therapy could result in the senescence of ASCs, thereby compromising their viability and therapeutic efficacy. This study aims to...

CONCLUSION: This study identifies SP1 and SEPHS2 as key genes linking selenium to brain aging, providing new insights into the role of selenium in brain aging and suggesting that these genes may represent potential biomarkers or therapeutic targets for brain aging and aging-related brain disorders.

Macrophage fate decisions during infection are commonly framed as receptor-proximal transcriptional choices. We propose that the functional outcome results from a "kinetic race," a dynamic proteostatic competition among protein synthesis, post-translational modifications (PTMs), and degradation. Building on experimental evidence of infection-induced proteostasis, we outline a conceptual "turnover-first" framework. In this model, we hypothesize that the ubiquitin proteasome system (UPS),...

Glucagon-like peptide-1 (GLP-1) receptor agonists have attracted interest as gerotherapeutics, yet clinical-trial evidence for their effects on biological aging is lacking. We report a post hoc exploratory epigenetic age analysis of a 32-week, randomized, double-blind, placebo-controlled phase 2b trial (NCT04019197) of semaglutide in adults with human immunodeficiency virus (HIV)-associated lipohypertrophy (semaglutide n = 45; placebo n = 39). The parent trial's primary endpoint was change in...

.The uterine decidua is a key component of the maternal-fetal interface, and its senescence may be an important contributing factor to recurrent pregnancy loss (RPL). Decidual senescence disrupts gestational homeostasis via cell cycle arrest, immune imbalance, and metabolic reprogramming, thereby potentially contributing to RPL. This review offers a new paradigm for understanding RPL etiology, with significant clinical value for improving reproductive outcomes.

Companion dogs (Canis lupus familiaris) offer a unique model for studying the gut microbiome and its relation to aging due to their cohabitation with humans, sharing similar environments, diets, and healthcare practices. Here, we present the Dog Aging Project (DAP) Precision cohort, a large population-wide study of the canine gut microbiome. This cohort encompasses over 900 dogs of diverse breeds, environments, and demographics living across the United States. Coupling fecal shotgun metagenomic...