Aging & Longevity

Hutchinson-Gilford progeria syndrome (HGPS) is a premature aging disorder affecting tissues of mesenchymal origin. Most patients harbor a c.1824C>T/p.G608= variant, commonly described as G608G, in exon 11 of LMNA that leads to aberrant splicing and production of the toxic progerin protein. In addition to cardiovascular, dermal, and adipose tissue deterioration, HGPS mouse models also develop progressive bone dysplasia that occurs in patients. Here we characterize the efficacy of in vivo mutation...

Aging kidneys exhibit accumulation of senescent cells together with sterile low-grade inflammation. However, the spatial organization of senescence-associated immune cell accumulation in the aging kidney remains poorly defined. We systematically analyzed kidneys from young, middle-aged, and aged mice, focusing on the spatial relationship between senescent tubular cells and distinct immune cell populations. Senescent tubular cells showed significant local enrichment of immune cells, with...

Prolonged crises expose older adults to chronic psychological and social stress, irregular nutrition, reduced physical activity, reduced access to health care, and interruptions in treatment of chronic disease. Together, these factors can compound age-related vulnerabilities and increase the risk of metabolic deterioration, multimorbidity and functional decline. This Perspective argues that prolonged crises should be viewed not only as social or psychological events, but also as conditions that...

Is there a limit to human lifespan? We examine upper-tail lifespan dynamics in 46 countries using reliable period life-table data. The characteristic life ( α ), the model-based upper-tail parameter ( ω ), and their interval ( δ = ω - α ) are estimated annually from the 1990s onward. Across countries, α increases steadily, whereas ω declines or stabilizes and δ narrows, a pattern consistent with postponed and increasingly concentrated late-life mortality rather than unlimited upper-tail...

Workplace stress is an increasingly recognized determinant of both workforce well-being and healthy aging. However, few longitudinal studies have systematically integrated stress assessment into large occupational cohorts with an explicit focus on aging processes. The Semmelweis Study, launched in 2024, addresses this gap by embedding validated stress assessment tools into a comprehensive, multidisciplinary framework designed to explore the biological, psychological, and social determinants of...

Multiomic profiling provides a comprehensive physiological overview at the molecular level, but understanding of its spatiotemporal dynamics remains limited in human populations. We profiled longitudinal whole-blood gene expression and metabolite levels in 335 females over 8 years. Levels of 5061 genes and 181 metabolites changed over time, with individual trajectories often diverging from population-level trends. Longitudinally variable genes showed cell type specificity and enrichment for...

CONCLUSION: Rare and common variants in AD- and neurodegenerative biomarker-associated genes with increased frequency in India compared to other populations may impact blood levels of neurodegenerative biomarkers in South Asians.

Insulin-like growth factor 1 (IGF1) signaling plays a critical role in brain function and declines significantly with aging. However, how these changes occur across different brain regions and cell types, and how they contribute to behavioral dysfunction, remains poorly understood. The prefrontal cortex (PFC), a key regulator of cognitive, emotional, and social behaviors, is particularly vulnerable to age-related changes. Here, we investigated age-associated changes in IGF1 and its receptor...

Falls, delirium and functional decline are commonly treated as distinct geriatric outcomes despite sharing vulnerabilities in sensory integration, gait regulation, attention and physiological reserve. We propose silent neurovestibular frailty as a conceptual model describing a latent ageing phenotype in which vestibular dysfunction, dual-task gait deterioration and sensitivity to cognitive load interact before overt disability becomes apparent. This construct is presented as a...

OBJECTIVES: This study explored the mediation and moderation effects of social engagement on the relationship between hearing status and cognitive function among Mexican adults aged ≥ 50 years across a six-year period (2015-2021).

CONCLUSION: There is a high burden of geriatric depression among older adults with MSDs in southeastern Nigeria, driven by both clinical and social factors. These findings underscore the need for integrated mental and musculoskeletal health services, especially within primary care settings in low-resource contexts.

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Microglia are the resident macrophages of the central nervous system¹. In mice, microglia seed the brain during embryogenesis and can be maintained throughout life with minimal input from adult haematopoiesis^(2-4). The origins of human microglia are less clear, but recent evidence suggests that bone-marrow-derived cells contribute to the human microglial pool in certain individuals^(5-9). Here, to investigate the ontogeny of human microglia, we develop an approach that uses the collection of...

Solution processing remains the dominant route to high-performance perovskite/silicon tandems, but it remains challenging to simultaneously achieve industrial scalability and long-term reliability^(1-3). Thermal evaporation is more industrially viable, yet it has not been successfully demonstrated for large-area perovskite/silicon tandems, largely due to the thermal degradation of formamidinium iodide (FAI) during high-temperature evaporation. Here we synthesize a formamidinium-based eutectic...

Pharmacological glucagon-like peptide-1 receptor (GLP-1R) activation reduces food intake and is an effective therapy for type 2 diabetes and obesity¹. The use of GLP-1 medicines has revealed pleiotropic beneficial effects beyond glucose and weight control^(2-5), but little is known about the underlying basis of the pleiotropic effects. Here, treatment of 20-month-old female C57BL/6 mice with the GLP-1R agonist semaglutide for 3 months improved physiological function, attenuated hallmarks of...

Chemotherapy-induced bone loss represents a major clinical challenge, particularly in aging populations, yet the contribution of cellular senescence to this process and its therapeutic potential remain incompletely understood. Here, we investigated the role of chemotherapy-induced cellular senescence in mediating skeletal deterioration following chemotherapy and evaluated the therapeutic potential of senolytic treatment. Young (3-month-old) and aged (20-month-old) male and female mice were...

Excessive alcohol consumption accelerates cardiovascular aging by promoting oxidative stress, inflammation, lipid dysregulation, fibrotic remodeling, and loss of ventricular-vascular reserve. PCSK9, a key regulator of cholesterol metabolism, has emerged as a mediator of age-related cardiovascular dysfunction and alcohol-associated liver and neurovascular injury. We investigated whether PCSK9 inhibition protects against alcohol-induced cardiovascular dysfunction and associated cardiac-hepatic...