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Whether a decline in taurine drives aging is debated, and despite high millimolar intracellular concentrations, its function as a potential guardian of cytosolic homeostasis is unclear. Here, we show that aging increases circulating taurine concentrations in humans and mice. Further elevating taurine in aged mice enhances health span, engaging anti-inflammatory pathways previously linked to youthfulness, and reduces mortality from sepsis and inflammasome-mediated inflammation, suggesting an...

Physical activity promotes health primarily by decelerating the aging process. Bone is one of the tissues capable of sensing mechanical force and can adapt to different physical demands. However, its role in whole-body aging is unknown. We found that reduced mechano-sensing in osteocytes, caused by deletion of the mechanosensory channel, Piezo1, accelerated whole-body aging in mice. Dynamic tibial axial loading (DTAL) in mice at 20-24 months of age extended both healthspan and lifespan...

Neurodegenerative diseases are emerging as an important consequence of population ageing in sub-Saharan Africa (SSA), but their scientific relevance extends beyond a projected rise in case numbers. SSA combines exceptional human genomic diversity with marked heterogeneity in vascular and metabolic risk, infection, nutrition, occupational exposures, air pollution, and access to health care. This combination creates an underused setting in which to study why biological ageing produces...

CONCLUSIONS: The present findings may provide mechanistic insights into the development of nutritional strategies to attenuate age-associated anabolic resistance and improve skeletal muscle oxidative metabolic function.

CONCLUSION: The Fasting ENHANCE study protocol outlines the methodology for evaluating the effect of TRE on cognitive and metabolic health in older adults with SCD. Results will inform future nonpharmacological interventions aimed at attenuating cognitive decline.

Epstein-Barr virus (EBV)-associated gastric cancer (EBVaGC) is a molecularly distinct, highly immunogenic gastric cancer subtype, yet the role of tertiary lymphoid structure (TLS) during therapy remains unclear. Using a large locally advanced EBVaGC cohort (144 samples), combined with spatial transcriptomics (11 samples) and a single-cell atlas (77 samples), we show that EBVaGC exhibits enhanced TLS formation compared with EBV-negative gastric cancer, with invasive-margin TLS (IM-TLS) predicting...

Acute myeloid leukemia (AML) is a heterogeneous disease characterized by a broad spectrum of molecular alterations that influence clinical outcomes. TP53 mutations define one of the most lethal subtypes of AML, driving resistance to nearly all available treatment modalities, including venetoclax plus azacitidine (VenAza). Yet, the molecular basis of this resistance, beyond affecting transactivation of BCL-2 family genes, has remained elusive. Here, we demonstrate that VenAza treatment leads to...

Biostimulatory dermal fillers are widely used for skin rejuvenation, but how particle physicochemical properties regulate fibroblast-macrophage interactions and collagen remodeling remains unclear. We compared calcium hydroxylapatite (CaHA), polycaprolactone (PCL), spherical poly-L-lactic acid (PLLA-Sp), and irregular PLLA fragments (PLLA-Ir) through comprehensive characterization (SEM, FTIR, zeta potential, AFM, roughness, tapped density, rheology in HA matrices) along with in vitro (human...

Nicotinamide adenine dinucleotide (NAD) is a metabolic cofactor regulating energy metabolism, epigenetics, DNA repair, and signaling. Although NAD declines with vitamin B3 deficiency, disease, and aging, systemic consequences of chronic depletion remain unclear. Here, we characterize an in vivo model of inducible NAD deficiency using acquired niacin dependency (ANDY) mice, in which NAD synthesis becomes dependent on dietary niacin. On a niacin-free diet, ANDY mice developed widespread tissue NAD...

The implementation of CMS age-friendly care initiatives has created new opportunities for geriatricians to shape clinical care, quality improvement, education, and health system strategy. A geriatrician's unique contribution extends beyond managing medical complexity; it lies in applying expertise in aging physiology, functional change, psychosocial context, heterogeneity, prognosis, patient priorities, and ageism to clinical and organizational decision-making. Geriatrics expertise must be...

CONCLUSIONS: This study lays the foundation for developing standardised proxy ageing-in-place indicators to monitor how older people with or at risk of frailty are living in their homes and communities. Future directions include assessing feasibility of capturing non-clinical indicators routinely; applying these indicators to guide personalised targeted interventions; and leveraging technology-related indicators to improve digital inclusion and literacy in older people to support...

CONCLUSIONS: Widowhood exerts a significant positive impact on hospitalization risk among Chinese older adults, with heterogeneous effects across cohorts and calendar time and an immediate but non-persistent dynamic pattern. These findings highlight the need for targeted interventions, particularly during the immediate year following spousal loss and for specific high-risk cohorts. Practical steps include enhancing family-based health management support and optimizing healthcare accessibility...

CONCLUSIONS: In this selected sample, functional fitness, particularly aerobic endurance and lower-limb flexibility, accounted for the largest share of explained variance, whereas EHBMS-assessed beliefs added negligible variance. Because no analysis formally compared predictor domains, this reflects relative incremental contribution, not a tested difference. The null belief findings warrant caution because self-efficacy was unmeasured and several subscales showed ceiling effects.

Genetic trade-offs can constrain life-history evolution resulting in the evolution of ageing. Reduced insulin/insulin-like signalling (rIIS) improves somatic maintenance and dramatically increases lifespan in Caenorhabditis elegans, but the effects on fitness are unclear. Here we used a novel experimental approach to show that, contrary to the prevailing paradigm, rIIS via daf-2 RNAi during development can improve development, reproduction, survival, individual fitness, and population growth...

The RNA-binding protein T cell intracellular antigen-1 (TIA1) regulates cellular stress responses and tau pathology, key contributors to the pathophysiology of tauopathies, including Alzheimer's disease (AD). TIA1 acts in peripheral monocytes to inhibit inflammation, but its function in central microglia, critical to neuroinflammation and disease progression, remains unknown. Here, we crossed TIA1 microglial conditional knockout (cKO) mice (using a Cx3cr1-driven Cre element) with the PS19 P301S...

Pathological accumulation of MAPT/tau protein is a defining feature of Alzheimer disease (AD) and related tauopathies, highlighting the need to identify druggable regulators of MAPT/tau clearance. Using Drosophila behavioral assays focused on cytoskeletal remodeling pathways dysregulated in AD, we identified genes whose genetic modulation mitigates MAPT/tau-induced behavioral deficits. These modifiers were validated by histopathology and mechanistically examined in human tauopathy cell models to...

There is little causal evidence on factors that can protect individuals against Alzheimer's Disease and Related Dementias (ADRD) risk. We study the causal effect of education on ADRD, exploiting a regression discontinuity generated by a compulsory schooling reform. ADRD was ascertained based on medical history, hospital records, and death registries, addressing concerns about selective sample attrition. We find that education reduces incidence of ADRD. Using molecular genetic data, we show that...

The growing evidence that existing cardio-renal-metabolic therapies, such as GLP-1 receptor agonists and SGLT2 inhibitors, confer all-cause mortality benefits has positioned them as the first wave of potential gerotherapeutics. However, repurposing these drugs for a lifespan extension indication remains constrained by trial duration, misaligned incentives, and the lack of a viable regulatory path. We highlight two parallel strategies to address these barriers: (1) identifying and validating...

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The steroid hormone dafachronic acid may carry the effects of reduced mTOR activity between tissues to coordinate metabolism and longevity across the body.