Aging & Longevity

CONCLUSIONS AND IMPLICATIONS: Machine learning models demonstrated substantial predictive performance with interdisciplinary team-determined follow-up interval categories among community-dwelling older adults. Explainable artificial intelligence analyses highlighted the contribution of multidimensional geriatric assessment domains to individualized follow-up planning. These findings support the potential role of artificial intelligence-assisted decision support in home-care scheduling, although...

Meningeal (dural) lymphatics are essential for cerebrospinal fluid (CSF) clearance to cervical lymph nodes, yet the precise pathway is incompletely understood. Using a multifaceted approach in mice, we examined tracer dynamics and the CSF outflow pathway from the subarachnoid space (SAS) to the nasal mucosa and identified a discrete arachnoid region surrounding the olfactory bulbs with abundant fenestrations. Similar arachnoid fenestrations were found in cynomolgus monkeys. Fluorescent tracers...

Senescent cells in the aging and diseased brain are increasingly recognized as highly heterogeneous catalysts of dysfunction, originating from diverse cell types and characterized by wide-ranging molecular signatures and functional outcomes. Additionally, technological advances in single-cell transcriptomics and mouse modeling have helped reframe senescence from a static fate to a dynamic trajectory that is heavily influenced by evolving environmental cues. In this review, we identify key hubs...

Changes in the gut microbiota occur throughout the human lifespan, and maintaining microbial homeostasis plays a critical role in promoting healthy aging. In recent years, substantial progress has been made in elucidating the mechanistic links between aging and microbiota remodeling, highlighting the central role of microbiota-host interactions in regulating immune responses and maintaining metabolic homeostasis. These findings provide new potential targets for the precision prevention and...

Chronic inflammation increases with age and contributes to cancer progression and therapeutic resistance, yet the mechanisms underlying this process remain incompletely understood. Here, we identify an increased frequency of pro-inflammatory myeloid cells in aged mice and humans, characterized by elevated production of IL-1α, IL-1β, IL-6, and TNF-α. These cells are enriched in the breast tumor microenvironment and are associated with accelerated tumor progression. Using heterochronic parabiosis...

Early-life nutrition is linked to adult brain health, yet evidence from quasi-experimental studies remains scarce. Leveraging the UK's historical sugar rationing as a natural experiment, we examined whether early-life sugar restriction reduces the risk of neurodegenerative and psychiatric disorders in later life. Among 60,394 UK Biobank participants (born 1951-1956), three groups were defined: in-utero-only, in utero plus 2 years, and non-rationed controls. Compared with non-rationed...

The gut virome is emerging as a key contributor to host physiology, yet it remains underexplored relative to the gut bacteriome. Despite comprehensive viral catalogs for the human gut, comparable resources for mice, the principal model organism in biomedical research, remain lacking, limiting our understanding of virome-host interactions and their implications for host health and disease. Here, we present Mouse Reference Gut Virome (MRGV), a comprehensive catalog comprising 109,778 viral genomes...

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...