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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...

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.

Engineered fluids could extract metals from fracked reservoirs, supplying materials for solar cells and electric vehicles