Aging & Longevity

Aging is accompanied by chronic low-grade inflammation which has been associated with cognitive decline. Physical activity might regulate plasma levels of inflammatory-related proteins and may contribute to cognitive benefits, although the underlying mechanisms remain poorly understood. This exploratory secondary analysis aimed to evaluate whether different physical activity modalities were associated with distinct inflammatory-related plasma proteomic signatures in healthy older adults and to...

Lower urinary tract symptoms (LUTS) are associated with older age and mobility limitations. We evaluated whether energetic determinants of mobility-maximum oxygen consumption (VO(2)peak), energetic cost of walking (EC(w)), and cost-capacity ratio (CCR) were associated with LUTS in community-dwelling older adults. We used baseline data from 629 participants aged ≥ 70 years in the Study of Muscle, Mobility and Aging. The 10-item LURN Symptom Index (LURN SI-10; range: 0-38, higher = worse) assessed...

Low back pain is a leading cause of disability worldwide. While non-specific low back pain accounts for the majority of cases, older adults are at increased risk of pathological and structural causes related to age-associated spinal degeneration, including intervertebral disc degeneration. Despite widespread use, conventional diagnostic imaging often fails to reliably identify pain-generating sources. Treatment decisions remain challenging, with many current interventions providing limited...

The ovarian microenvironment is a dynamic target of aging and highly responsive to metabolic and dietary stressors. Western diets (WD) and high-fat diets (HFD) promote obesity and systemic metabolic dysfunction. However, whether these diets induce remodeling of the ovarian microenvironment remains unclear. In this study, we investigated how distinct dietary patterns influence metabolic homeostasis, estrous cyclicity, ovarian reserve, and stromal remodeling in female mice. Three-month-old C57BL/6...

Nicotinamide adenine dinucleotide (NAD⁺) is central to energy metabolism, redox reactions, and cellular signaling. However, human evidence linking circulating NAD⁺ concentrations to frailty remains limited. We examined the association of whole-blood NAD⁺ concentration with frailty in community-dwelling older adults. This cross-sectional analysis included community-dwelling adults aged ≥ 65 years from the 2025 Itabashi Longitudinal Study on Aging. Frailty was assessed using the revised Japanese...

The distinction between healthy and pathological ageing has led to the concept of vitality capacity, which can be understood as the body's physiological reserve and estimated using 12 biomarkers distributed across three domains: immune and stress response, energy and metabolism, and neuromuscular function. This physiological reserve may be preserved by lifelong physical activity. This exploratory cross-sectional study aimed to examine the relationship between vitality capacity and lifelong...

Clonal haematopoiesis (CH) is driven by somatic mutations in haematopoietic stem cells that generate clonal populations detectable in peripheral blood and is present in 10-20% of individuals over the age of 65. Mutations in DNMT3A and TET2 are the most common drivers and have been linked to inflammatory phenotypes and increased risk of haematologic and cardiovascular disease. However, the cell-intrinsic mechanisms connecting these mutations to inflammatory signalling remain incompletely...

Aging is a major risk factor for cardiovascular disease, but the role of the cardiac lymphatic vasculature in this process remains poorly understood. Here we show that aging reduces cardiac lymphatic vessel density in humans and mice and induces structural remodeling characterized by tighter, zipper-like endothelial junctions. These changes are associated with immune cell infiltration, fibrinogen and amyloid accumulation, and myocardial edema. Selective reduction of cardiac lymphatics in young...

Activation of microglia is a prominent feature of amyotrophic lateral sclerosis (ALS), a neurodegenerative disease that leads to the death of motor neurons. A key component of this activation is elevated expression of the TAM receptor tyrosine kinases Axl and Mer (gene name Mertk). Here we show that germline and microglial-restricted inactivation of the Axl and Mertk genes in the SOD1^(G93A) mouse model of ALS leads to an extension of lifespan, which is tied to the preservation of cholinergic...

Traumatic brain injury (TBI) is a significant public health concern, particularly in aging populations. While advanced age and frailty affect outcomes after TBI, the independent effect of frailty on long-term outcomes in geriatric TBI patients remains poorly understood. We hypothesized that higher disease-specific frailty is independently associated with poor long-term outcomes and quality of life following TBI. To determine whether a TBI-specific frailty index assessed at presentation is...

Host-associated microbiomes often display host specificity and heritability, yet the evolutionary processes under which such structured communities first emerge are still unclear. In particular, the conditions by which intergenerational (i.e., vertical) transmission of microbes can evolve and generate host-specific microbiomes are still unresolved. Here, we present an eco-evolutionary theory of microbiome assembly under minimal assumptions of microbial dynamics (i.e., neutrally driven by...

Understanding the molecular basis of neurodegeneration requires a comprehensive map of the genome's protein-coding output. Although thousands of small open reading frames (ORFs) are translated in the human brain, proteomic evidence for their encoded microproteins (MPs) (≤150 amino acids (aa)) remains limited. Here, we present a brain MP atlas that integrates transcriptomics, mass spectrometry and deep-learning-predicted spectra across more than 600 postmortem frontal cortex samples with and...

Somatic mosaicism is increasingly recognized as a pervasive feature of the human brain and a potential contributor to neurological disease across the lifespan. Unlike germline variants, somatic variants arise post-zygotically and are unevenly distributed across regions, cell types and even individual neurons, enabling focal biological effects that can scale to network-level dysfunction. In this Review, we synthesize current evidence that developmental timing, clonal architecture and...

Sleep is increasingly recognised as a potentially modifiable factor in cognitive ageing, but evidence is often limited by cross-sectional designs, single sleep measures and global cognitive outcomes. This study examined whether multiple sleep characteristics (device-based and self-report) were associated with domain-specific cognitive function across repeated observations in community-dwelling adults aged 55 years and older. Adults aged ≥ 55 years were assessed at three time points over 2 years...

Tobacco smoking is a critical modifiable risk factor for age-related diseases and mortality. Although smoking cessation is known to improve health outcomes, whether smoking-induced biological aging is reversible upon cessation remains unclear. We investigated the associations of smoking status and cessation duration with epigenetic age acceleration (EAA) using multi-generational DNA methylation clocks. We analyzed data from 1,911 adults aged 50-84 years in the National Health and Nutrition...

Chronic occupational stress is increasingly recognized as a modifiable accelerator of biological aging, yet it remains underappreciated as a target of geroscience-informed public health intervention. This review reframes workplace stress as a life-course determinant of aging trajectories and introduces a translational framework that positions occupational environments as platforms for promoting healthy aging. Drawing on insights from the Semmelweis Study, a large longitudinal occupational...

Rapid population aging has markedly increased the exposure of elder humans to invasive mechanical ventilation (MV). Mounting evidence suggests that aging fundamentally alters pulmonary structure and stress responses, predisposing the aged lung to ventilator-induced lung injury (VILI). However, the biological basis of this heightened vulnerability remains insufficiently synthesized. The review was conducted in accordance with the PRISMA 2020 guidelines. To this end, PubMed, Web of Science, and...

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) reduce major adverse cardiovascular events, all-cause mortality, and systemic inflammation in randomized controlled trials, with effect sizes exceeding those predicted from glycemic and weight-related improvements alone. The convergence of these findings with a maturing body of evidence linking metabolic dysfunction to accelerated epigenetic aging has prompted renewed interest in GLP-1 RAs as candidate gerotherapeutic agents. The present...

Physical multimorbidity and loneliness are increasingly recognised as public health concerns, but the nature of their potential relationships remains unclear. Here we report bidirectional associations between physical multimorbidity and loneliness in middle-aged and older adults and the mediating role of social inactivity. Longitudinal data from adults aged ≥45 years are analysed across 19 countries from five prospective cohorts: US Health and Retirement Study; English Longitudinal Study on...

This study investigated environmental justice by developing and comparing four contemporary urban segregation typologies (persistent exclusivity, persistent disadvantage, recent gentrification, and recent displacement-hosting) with historical Homeowners' Loan Corporation (HOLC) zones and 104 variables spanning the natural and built environments, pollution, environmental hazards, health, and disability. We applied principal component analysis to the 2010 and 2020 American Community Survey and the...