Aging & Longevity

Senescence, the endpoint of normal cells' replicative lifespan, is accompanied by a complex sequence of molecular events. One such event is the dramatic reorganization of CTCF into senescence-induced clusters (SICCs). However, the molecular determinants, genomic consequences and functional purpose of SICCs remain unknown. Here we combine three-dimensional genomics, super-resolution imaging, DNA tracing and functional assays with modeling to dissect SICC emergence. We find that, on senescence...

Understanding the links between metabolism, ageing, and age-related phenotypes may clarify the role of ageing in disease onset and improve risk prediction. We conducted a cross-cohort assessment of biological age using broad-spectrum LC-MS metabolomics of 3,686 plasma samples in 2,295 participants, aged 20-89, from the UK Airwave study (N = 960) and the Irish Longitudinal Study of Ageing (N = 1,335). The nucleoside N(2),N(2)-dimethylguanosine, C-glycosyltryptophan, bile acid glucuronides, and...

Hypertension is a hallmark of vascular aging; however, the epigenetic link between biological aging and blood pressure remains unclear. This epigenome-wide association study of hypertension examined 1528 Korean adults (896 normotensive, 632 hypertensive) from the Korean Genome and Epidemiology Study using the Illumina MethylationEPIC 850K array. Overall, 53 differentially methylated positions and 10 differentially methylated regions were identified, with the top region mapping to HIVEP3, an...

Aging is accompanied by a decline in physiological function and increased vulnerability to disease, with mitochondrial dysfunction and epigenetic alterations recognized as key hallmarks. Nicotinamide riboside (NR), a vitamin B3 precursor to NAD^(+), and high-intensity interval training (HIIT) have both been proposed to ameliorate aging-related mitochondrial decline, but their effects on skeletal muscle epigenetic aging are not fully elucidated. Here, we assessed the impact of 5-month NR...

CONCLUSIONS: Among very old Norwegian adults, greater muscular strength was associated with a lower risk of severe fall injuries. Our findings provide clinically interpretable strength thresholds that may support fall injury risk assessment and targeted prevention strategies among the oldest old.

CONCLUSIONS: In summary, the different brain aging patterns, each based around specific underlying circuits, may serve as neuroimaging biomarkers for understanding the neural aging mechanisms in commonly occurring brain disorders. Future studies should test whether these disorder-specific brain aging patterns can serve as useful biomarkers to guide critical clinical decision-making.

Reproductive aging in mice leads to estropause, characterized by estrous cycle irregularity and eventual cessation, yet its underlying mechanism remains unclear. Here, we present a comprehensive single-cell atlas of mouse ovaries across precisely defined reproductive stages-from young (regular cycling) through the estropausal transition (regular vs. irregular cycling) to post-estropause (acyclic)-and of ovary-specific senescent cells defined by high senescence-associated β-galactosidase...

During aging, hepatic structural, metabolic, and regulatory impairments collectively contribute to the decline of hepatic and systemic function. As a core hepatic physiological process, ammonia metabolism is essential for maintaining systemic nitrogen homeostasis. However, how ammonia metabolism is altered during aging, and whether these changes contribute to hepatic and systemic decline, remain insufficiently understood. In this review, current evidence linking hepatic ammonia metabolism to...

Sepsis-associated acute kidney injury (SA-AKI) is a common and devastating disease that has a significantly higher incidence and greater severity in elderly patients, but the molecular basis underlying SA-AKI in the elderly is largely unknown. Recent studies have proved autophagy as an intrinsic protective mechanism against AKI; however, the role and regulation of autophagy in aging kidneys remain unclear. Here we demonstrate that defective autophagy activation in aging kidneys is a key to their...

Atherosclerosis (AS) is closely linked to endothelial cell (EC) senescence and mitochondrial dysfunction, which impair vascular repair. Resveratrol (RSV) has antioxidant, anti-inflammatory, and pro-angiogenic effects, but its clinical use is restricted by poor bioavailability. This study aimed to construct a platelet membrane-coated resveratrol nanosystem (PM@RSV NPs) and investigate its mechanism of action in delaying the progression of AS by activating FOXM1 to improve mitochondrial function,...

CONCLUSIONS AND IMPLICATIONS: The global burden of HHD-related HF continues to rise, primarily fueled by population aging, though regional trends, and underlying drivers vary substantially. To address this challenge effectively, tailored prevention strategies should be implemented alongside global collaboration and equitable health care resource allocation, ensuring region-specific precision in HHD-related HF control.

Healthy aging is defined as remarkable longevity (beyond 90 years of age) accompanied by preserved functional status and absence of major clinical conditions. Although the incidence of cardiac arrhythmias, including atrial fibrillation (AF), increases with age, epidemiological studies revealed a paradoxical reduction of AF prevalence in centenarians compared to octogenarians and nonagenarians. Emerging evidence indicates that the apparent cardioprotection in healthy aging may be related to...

In a previous study, chloroquine (CLQ) administration extended lifespan in middle-aged male NMRI mice without systemic toxicity, challenging the view that blockage of autophagy is uniformly detrimental. Here, we evaluated a modified step-down intermittent CLQ regimen in aged female Sprague-Dawley rats designed to minimize long-term toxicity while maintaining biological activity. CLQ treatment significantly extended median lifespan and increased maximum lifespan by 19%. Treated rats exhibited a...

Aging is associated with increased oxidative stress, which leads to pathological vulnerability. Spermidine is a ubiquitous natural polyamine found across all living organisms studied so far and present in multiple food sources. In humans, spermidine levels decline with aging, and a possible connection between reduced endogenous spermidine concentration and age-related organ degeneration has been proposed. We outline recent studies that address the potential contribution of spermidine to...

Microglia, the resident macrophages of the CNS parenchyma, are recognized as highly plastic, transcriptionally diverse cells whose phenotypes are moulded by development, region, sex, age, genotype and environment. Advances in single-cell and single-nucleus transcriptomics, chromatin accessibility profiling, and spatial multi-omics have negated binary frameworks of 'resting versus activated' or 'M1 (pro-inflammatory) versus M2 (anti-inflammatory)' and revealed a multidimensional state space that...

Cytoskeleton is an important component of cell structure and function. In the cardiovascular system, it is involved in the remodeling process of a variety of cardiovascular diseases, including cardiac fibrosis, valvular disease, atrial fibrillation, thoracic aortic aneurysm and vascular stiffness related changes. Recent studies have shown that there is a significant synergy between cytoskeletal regulation and epigenetic processes. Notably, epigenetic alterations have been identified as one of...

Aging is a biologically tractable process. Telomerase reverse transcriptase (TERT) has emerged as an upstream regulator coordinating several hallmarks of aging across preclinical models. Beyond maintaining telomeres, TERT influences mitochondrial health, epigenetic regulation, inflammation and stem cell function. Multiple translational strategies are being explored to modulate TERT. In mice and human cell models, restoration of physiological-range TERT expression characteristic of younger cells,...

Unsupervised serious video games on the SmartMe&You home telemonitoring platform may enable the assessment of cognitive fluctuations in older individuals, with or without cognitive deficits. Here, we tested their validity in cognitively unimpaired older adults (Healthy) and patients with mild cognitive impairment and mild to moderate dementia due to Parkinson's disease (PDCD). Such validity was assessed using Mini-Mental State Examination (MMSE) scores and resting-state eyes-closed...

Epigenetic clocks derived from DNA methylation robustly predict biological aging, health, and mortality, yet differ substantially in their predictive profiles. The biological processes underlying these differences remain poorly understood. Using data from 3227 participants in the U.S. Health and Retirement Study, with contemporaneous DNA methylation and RNA-sequencing, we examined the five most widely used epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge, and DunedinPACE). We conducted...

CONCLUSIONS: Objectively measured sensory impairments were highly prevalent among US older adults and were associated with an increased risk of anxiety, but not depressive symptoms over a short follow-up duration. Self-reports considerably underestimated true prevalence of mild- to- moderate impairment, emphasizing the need for routine objective assessment in clinical practice and research.