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CONCLUSIONS: This study contributes to ageing research by examining sustained robustness, rather than frailty progression alone, as a longitudinal outcome in a large multinational cohort. By identifying behavioral, psychosocial, and functional characteristics associated with sustained robustness, the study frames robustness as a measurable longitudinal outcome in ageing research and practice. These findings support a more balanced and positive conceptualization of ageing - one that emphasizes...

CONCLUSIONS: Frailty is an important risk factor for limitations in the ability to live independently, with a particularly high burden observed in the Baltic countries. Despite weaker associations with new limitations compared with the Nordic countries, the higher prevalence of frailty, poorer health profiles, and lower levels of physical activity in the Baltic countries highlight a substantial need for early identification and targeted prevention.

Regenerative capacity varies widely across animals, yet aging is often accompanied by declining tissue homeostasis and regenerative potential. In many species, regeneration of complex structures relies on epimorphic programs that form a blastema, coordinating cell proliferation and pattern reorganization after injury. Although aging-associated regeneration defects have been documented in several bilaterian models, how aging shapes regeneration in early-branching metazoans with robust...

Aging exacerbates the incidence of discogenic chronic low back pain by excessive inflammation and immune cell presence. Aging reduces intervertebral disc (IVD) Wnt signaling, which is associated with IVD cell differentiation, IVD cell proliferation and anti-inflammatory signaling. However, it is unclear how in vivo Wnt signaling-absent IVD cells, which model aged IVD cells, regulate chemotactic signaling and immune cell recruitment. We hypothesized that Wnt signaling-absent IVD cells attenuate...

Ageing biomarkers quantify molecular, physiological or functional features that vary between individuals as they age and may improve prediction of health outcomes beyond chronological age. Recently, plasma proteomics have been used to estimate the biological ages of 11 human organs. Although accelerated organ ageing is associated with higher mortality risk, systematic benchmarking against established ageing biomarkers is lacking. Here, we pursued two complementary aims. First, we benchmarked...

People who followed the MIND diet more closely showed slower brain shrinkage and less grey matter loss over time, with the strongest differences equivalent to about 2.5 years of delayed brain aging. Berries and poultry were linked with healthier brain changes, while sweets and fried fast foods were associated with greater tissue loss.

More than half of 16,000 apparently healthy adults had signs of atherosclerosis, with arterial plaques already detectable in about 1 in 13 people ages 18 to 29. Researchers say directly imaging the arteries could reveal hidden cardiovascular disease years or even decades before symptoms appear.

What sounds like a jumble of noise is actually a group signal

α-synuclein is a pre-synaptic protein implicated in synucleinopathies including Parkinson's disease, Parkinson's disease dementia, and dementia with Lewy bodies, where it accumulates in intracellular aggregates termed Lewy bodies and Lewy neurites. Recent studies have reported that α-synuclein undergoes phase separation to form biomolecular condensates both in vitro and in mammalian cells. α-synuclein condensates are thought to contribute to disease through progressive aggregation. Here we show...

Aging and Alzheimer's disease (AD) are accompanied by alterations to large-scale communication patterns in the brain, which can be tracked in vivo using functional connectivity. The location, direction and relevance of these changes remain widely debated, although they are rarely studied in the context of whole-cortex communication dynamics. Here, in two independent cohorts (BioFINDER-2, N = 973; Alzheimer's Disease Neuroimaging Initiative, N = 129), we show that functional connectivity changes...

Skeletal muscle hypertrophy is a hallmark of resistance training that improves health and longevity. However, despite physiological differences between sexes and fiber types, the underlying proteome changes with resistance training have not been studied in a sex- and fiber type-specific manner. Herein, we show sex- and fiber type-specific remodeling of the human skeletal muscle proteome following 8 weeks of resistance training. Type II fibers exhibited much greater adaptations across both sexes,...

Aging and Alzheimer's disease (AD) are accompanied by alterations to large-scale communication patterns in the brain, which can be tracked in vivo using functional connectivity. The location, direction and relevance of these changes remain widely debated, although they are rarely studied in the context of whole-cortex communication dynamics. Here, in two independent cohorts (BioFINDER-2, N = 973; Alzheimer's Disease Neuroimaging Initiative, N = 129), we show that functional connectivity changes...

Cellular senescence plays an important role in hepatic inflammation and fibrosis^(1-3). However, whether senescence represents a potential therapeutic target in humans with metabolic dysfunction-associated steatohepatitis (MASH) remains unexplored. Here we report the results of a phase-2, double-blind, randomized, placebo-controlled trial of intermittent senolytic therapy with dasatinib plus quercetin (D + Q) in participants with fibrotic MASH. Thirty-one participants (median age 56 years; 76%...

Oxygen sensing signaling is mainly mediated by EGLN prolyl hydroxylases, which plays important roles in physiology and diseases. Among them, EGLN2 plays an oncogenic role in breast cancer. However, the development of isoform-selective EGLN2 inhibitors remains a major challenge. Here, we report the identification of A10P3C, a small-molecule inhibitor that exhibits high potency and exceptional selectivity toward EGLN2. Guided by conformational sampling, ensemble-docking-based...

Osteoarthritis (OA) is a degenerative joint disease, the progression of which is accelerated by systemic metabolic stress. Here, we identified a neuroendocrine pathway through which hypertension accelerates OA pathogenesis in joints predisposed by mechanical injury or aging. Nationwide cohort analyses and hypertensive mouse models demonstrated that elevated blood pressure exacerbates OA pathogenesis. OA-primed chondrocytes up-regulated arginine vasopressin (AVP) receptor 1A (AVPR1A), rendering...

Sex differences have traditionally been attributed to gonadal hormones, but accumulating evidence shows that sex chromosomes exert distinct, cell-autonomous effects on health, aging, and disease. XX and XY complements alter gene dosage, epigenetic programming, immune signaling, metabolism, and cellular stress responses, which shape aging and disease trajectories in women and men. This Review integrates mechanistic advances in sex chromosome biology-including escape from X chromosome...