Aging & Longevity

Aging is accompanied by molecular hallmarks conserved from yeast to humans. One such hallmark, senescence, is an irreversible nondividing state that promotes aging. We previously reported that mutants of the yeast Anaphase Promoting Complex (APC) shorten the lifespan of both dividing and nondividing cells. Here, we propose that activation of the APC will promote the maintenance of quiescent yeast cells, thereby delaying senescence and aging. We observed that APC activity in aging quiescent cells...

The global incidence and mortality of nontuberculous mycobacterial infections have risen sharply with population aging. In some regions, they are now surpassing Mycobacterium tuberculosis complex infections, imposing a substantial clinical and economic burden. Because nontuberous mycobacteria exhibit species-level heterogeneity and require prolonged culture for identification, their diagnosis remains slow and is frequently inaccurate. Here, we describe a multiplexed clustered regularly...

Structural reconstruction is a major cause of heterogeneous catalyst deactivation, yet elucidating the restructuring mechanism remains difficult due to underresolved dynamics. Here, by introducing pseudotime, we recover dynamics and identify the key determinant of nanoparticle sintering from ex situ electron microscopy alone, beyond the general view that postmortem observations provide only end-state structures. Pseudotemporal ordering of SiN(x)-supported gold across asynchronous aging states...

Age-related microvascular dysfunction disrupts nutrient homeostasis and waste clearance, leading to organ failure. However, a critical gap remains in our understanding of the specific molecular drivers of vascular deterioration and how they orchestrate organism-wide aging. Here, we identify progressive activation of the CCAAT/enhancer-binding protein β (C/EBPβ)/asparagine endopeptidase (AEP) pathway in aging vascular endothelial cells contributes to vascular degeneration and lifespan reduction....

Successful cognitive aging (SCA) describes the preservation of cognitive abilities into advanced age, but its neural basis remains incompletely understood. Metabolic and pathological evidence implicates the posterior cingulate cortex (PCC) as a key region supporting cognitive resilience. However, functionally distinct PCC subregions have rarely been examined using complementary structural, microstructural, and functional imaging measures. In this cross-sectional secondary analysis of publicly...

Age-related hearing loss (ARHL) is the most common sensory disorder in older adults. Current hearing interventions, including hearing aids and cochlear implants, face limitations in accessibility and adherence. Therefore, efforts have been devoted to elucidating the molecular mechanisms underlying cochlear aging and identifying effective therapeutic targets for ARHL. This review summarizes several molecular mechanisms implicated in cochlear aging and ARHL, including autophagy dysregulation,...

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...