Aging & Longevity

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...

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...

Menopause is an important biological transition with up to 72 symptoms that shapes aging trajectories across organs and encompasses ~40% of the female lifespan. Although menopause awareness is increasing, research on strategies for menopause symptom management and optimizing health in the postmenopausal period is lacking. This Review highlights that menopause characteristics, such as type, timing, and symptom burden, influence health outcomes and later-life disease risk. Similarly, menopause...

Longevity is taking off, but regulatory oversight is essential to determining what works-and what doesn't.

T helper 9 (Th9) cells show promise for adoptive cell therapy (ACT) against solid tumors. However, clinical application faces challenges regarding their persistence in the tumor microenvironment (TME). We observed that tumor growth gradually reduced glucose concentrations in the TME, accompanied by a decline in transferred Th9 cells and their effector functions, due to Th9 cell senescence. Restoring glucose concentrations suppressed Th9 cell senescence, thereby improving their persistence....

CONCLUSIONS: We showed that the protocol is feasible and agreeable to participants and their families. A comprehensive phenotype dataset was established, and DNA samples were stored for subsequent genomic analysis. Centenarians exhibited a broad spectrum of cognitive profiles, from preserved cognition to severe dementia. Some data were unavailable, which should be considered in light of the study design and the characteristics of the cohort. These findings will eventually allow investigation of...

Age-related and noise-induced hearing loss reflect progressive cochlear degeneration and adaptive changes in central auditory pathways, yet their joint effects on auditory brainstem response (ABR) amplitudes and auditory thresholds remain unclear. We developed the Auditory Homeostatic Dynamics Model (AHDM), a three-state ordinary differential equation model of hair-cell sensory function, cochlear synaptic integrity, and activity-dependent central compensation across low-, mid-, and...

Persistent low-grade inflammation, oxidative stress, cellular senescence, and disturbance of cellular homeostasis are all connected with ageing and can lead to the development of age-related diseases. Ferroptosis, an iron-dependent type of controlled cell death, has been linked to these processes more and more. It may represent a key connection between inflammation, oxidative damage, and tissue failure as people age. With a focus on neurodegenerative, cardiovascular, metabolic, pulmonary, and...

CONCLUSION: Health literacy is a key factor of active and successful ageing. To promote active ageing, older adults care centres should prioritise health literacy.

Hutchinson Gilford progeria syndrome (HGPS) is a fatal premature aging disorder caused by pathogenic farnesylated lamin A variants that disrupt nuclear architecture and DNA repair. Current therapies, including farnesyltransferase inhibitors, provide only modest survival benefits and lack molecular specificity, while mutation-specific genome-editing strategies cannot address atypical laminopathies. Here, we develop Farnesylation Amino acid Targeted Editing (FATE), a mutation-agnostic base-editing...

Estrogen Receptor alpha (ERα) is the primary driver in ER+ breast cancer and can be targeted using small molecules such as fulvestrant, a selective estrogen receptor degrader (SERD). Despite being approved over two decades ago and used regularly in post-menopausal women, its precise anti-tumor mechanism remains unclear, with several reports showing efficacy without the requirement for ERα degradation. To investigate the molecular basis of fulvestrant's action, we employed split intein-based µMap...