Aging & Longevity

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Sleep and circadian disturbances are associated with cognitive decline and dementia. Narcolepsy type 1 (NT1), characterized by severe sleep-wake disruption and loss of hypocretin, would therefore be expected to predispose individuals to premature brain aging. Yet available biomarker and neuroimaging findings do not consistently support this possibility, raising questions about the role of hypocretin in mechanisms linking sleep to neurodegeneration. Beyond maintaining wakefulness, hypocretin...

The increasing burden of dementia highlights the need for sensitive and ecologically relevant tools for early detection and intervention. Dual-task (DT) paradigms have emerged as promising approaches for assessing cognitive-motor alterations. This study aimed to map the 22-year evolution of DT research in cognitive aging using bibliometric analysis. We retrieved 1347 articles from the Web of Science Core Collection (January 2003-February 15, 2025) and analyzed them using CiteSpace. Co-citation,...

Lipids dynamically reside in multiple intracellular locations, and their organellar distribution is important for function. During brain aging, lysosomal lipid changes have been noted, but lipid identity, interactions, and functional relevance have not been characterized. We used mass spectrometry to assess longitudinal changes in the lipidome and proteome of lysosomal fractions from the murine cortex, from 3 to 24 months, followed by multi-omics factor analysis (MOFA) to identify factors...

Cryptovivipary and vivipary, referred to as (crypto)vivipary, occur across multiple angiosperm lineages and enable embryos to continue developing before dispersal. Yet, this trait raises a fundamental question: how are seed-specific abscisic acid (ABA) responses modulated to support continuous embryonic growth without compromising ABA-dependent vegetative stress tolerance? Here, integrating phylogenomic analyses of independently evolved (crypto)viviparous lineages with spatiotemporal...

Precise three-dimensional (3D) genome organization is crucial for regulating gene expression during development, yet its role in age-related transcriptional changes and physiological decline remains elusive. Here, we show that aging reshapes chromatin architecture and gene regulation in murine naive CD4^(+) T cells, a quiescent T cell population essential for adaptive immunity. Aged naive CD4^(+) T cells exhibit intrinsic transcriptional reprogramming marked by increased expression of...

INTRODUCTION: Aging is associated with alterations in white matter structure and decline in bimanual performance. These parallel changes may be interrelated, as previous studies have linked cerebral white matter properties to both motor and cognitive function. The cerebellum plays a central role in complex motor coordination and higher-order processes, yet age-related differences in cortico-cerebellar pathways remain insufficiently understood. This study therefore examined two major...

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.