Aging & Longevity

Physical activity (PA) is one of the most fundamental traits in the animal kingdom, has pervasive health benefits, and is genetically influenced. Using data from the Million Veteran Program, we conducted genetic analyses of leisure, work and home-time PA. For leisure, we included 189,812 individuals of European ancestry (SNP-based heritability (h²) = 0.083 ± 0.005), 27,044 of African ancestry (h² = 0.034 ± 0.017) and 10,263 of Latin American ancestry (h² = 0.083 ± 0.036) in a cross-ancestry...

With concerns about aging dams and nonstationary changes in hydrologic extremes (e.g., flooding), questions arise about whether existing dams may be at risk of failure and pose threats to society. Here, we analyzed 33 dams across the United States to investigate temporal trends in dam overtopping probabilities of annual maximum dam water levels. These dams were selected because of the availability of public domain long-term time series of uncontrolled water levels (50 years or longer). We...

The choroid plexus (ChP) is a complex ventricular structure that forms a semi-permeable barrier between the blood and cerebrospinal fluid (CSF). It is responsible for CSF secretion and clearance, contains macrophages, and is one of the few sites within the central nervous system (CNS) where T cells are present. Additionally, the ChP plays a role in detecting peripheral inflammation, which leads to the modulation of its epithelial cell function. Despite its critical importance in maintaining...

CONCLUSIONS: This study reveals that LST and MVPA may play a causal role in the process of aging. Accordingly, public health efforts to promote increased physical activity and reduce sedentary time can effectively combat accelerated aging.

The accumulation of senescent endothelial cells within the endothelium leads to vascular dysfunction. Independent studies have linked miR-217, a senescence-associated microRNA and FOXO3, a longevity factor, to cellular senescence in different study models. However, their roles and direct interaction in endothelial replicative senescence (RS) remain to be investigated. This study sought to investigate the role of miR-217/FOXO3 axis in endothelial cell senescence. Young and RS HUVEC models were...

Longitudinal studies provide conflicting evidence regarding the impact of vitamin D deficiency on cognitive performance in older individuals. The present study aimed to investigate whether vitamin D deficiency is a risk factor for poorer trajectories in global cognition and specific cognitive domains over a six-year follow-up period. This cohort study analysed data from 2625 participants aged 50 years or older from the English Longitudinal Study of Ageing. Vitamin D [25-hydroxyvitamin D,...

DNA-protein crosslinks (DPCs) are endogenous and chemotherapy-induced genotoxic DNA lesions and, if not repaired, lead to embryonic lethality, neurodegeneration, premature ageing, and cancer. DPCs are heavily polyubiquitinated, and the SPRTN protease and 26S proteasome emerged as two central enzymes for DPC proteolysis. The proteasome recognizes its substrates by their ubiquitination status. How SPRTN protease, an essential enzyme for DPC proteolysis, achieves specificity for DPCs is still not...

Smoking is one of the most recognized risk factors for pulmonary fibrosis (PF). However, the underlying mechanism is not well understood. This study reveals smoking increases the risk of developing idiopathic PF (IPF) and that smoked IPF patients exhibit higher levels of senescence markers than non-smoker IPF patients. Moreover, smoking enhances bleomycin (Bleo)-induced PF, along with obvious senescence of type II alveolar (AT2) cells. RNA-seq assay identifies cigarette downregulates protection...

CONCLUSIONS: This study is the first to establish normative reference values for PhA across the lifespan of a Korean population aged 10-80 years and the cutoff points for diagnosing sarcopenia in older adults.

CONCLUSION: Activities of Daily Living mediates the relationship between social participation and Self-rated Health. Attention should be paid to the Activities of Daily Living of older adults, with particular attention to those living alone and those who are chronically ill, and to social resources to enhance the social participation of older persons.

Proteins are essential biomolecules that play indispensable roles in maintaining cellular homeostasis and regulating systemic metabolic processes. Protein deficiency is closely associated with age-related chronic diseases. Our purpose is to reveal the reason of protein deficiency in the elderly and potential treatments. A systematic literature search mainly on human studies addressing gastrointestinal aging and amino acid homeostasis was conducted. This review investigated the effects of aging...

While a ketogenic diet (KD) can improve certain health parameters, evidence from murine and clinical studies suggests that these effects may be dependent on multiple variables. One understudied variable is the role of sex in the response to a KD. Here, we show that a KD-induced increase in p53, p21, and cellular senescence is only observed in male mice, except when they are given estrogen, and in female mice administered tamoxifen. Male, but not female, mice on a KD exhibit an increase in...

Accurate measurement of Drosophila feeding is vital for metabolic and aging studies, but current assays lack the throughput and sensitivity needed for large-scale screens. We introduce FlyPlate-BCA, a 96-well platform that combines automated single-fly tracking with BCA protein quantification for high-resolution, longitudinal intake measurements. FlyPlate-BCA detects a 0.1× nutrient dilution with 90% power using just four replicates, three times fewer than the capillary feeder (CAFE) assay. It...

Transformative neuropathology is redefining human brain research by integrating foundational descriptive pathology with advanced methodologies. These approaches, spanning multi-omics studies and machine learning applications, will drive discovery for the identification of biomarkers, therapeutic targets, and complex disease patterns through comprehensive analyses of postmortem human brain tissue. Yet critical challenges remain, including the sustainability of brain banks, expanding donor...

Aging-related declines in energy metabolism represent a key risk factor for the development of amyloid pathology, the earliest hallmark of Alzheimer's disease. Aging also contributes to the emergence of the second major hallmark, tau pathology, whose propagation is facilitated by pre-existing amyloid accumulation. The overlap of amyloid and tau pathologies ultimately leads to neurodegeneration and the onset of Alzheimer's disease-the most prevalent form of dementia. Recent findings underscore a...

CONCLUSIONS: The mortality risk is elevated among frail elderly individuals, particularly those who are underweight. Overweight exhibits a protective role in both frail and non-frail elderly persons.

DNMT3A is a critical regulator of hematopoietic stem cell (HSC) fate decisions and the most recurrently mutated gene in human clonal hematopoiesis (CH). DNMT3A is described as a DNA methyltransferase enzyme, but cells with DNMT3A loss of function show minor changes in DNA methylation that do not correlate with altered gene expression. To explore the possibility that Dnmt3a has DNA-methylation-independent functions in HSCs, we created an allelic series of mice with varying levels of...

CONCLUSION: Fall history independently predicts stroke risk in individuals with PS, highlighting the potential of fall prevention to reduce stroke burden in this population. This study provides novel evidence of a prolonged stroke risk trajectory in Asian PS cohorts, complementing Western studies focused on short-term post-fall risks. The study has several limitations. Self-reported falls may introduce recall bias and lack mechanistic details. Unmeasured confounders such as diet and medication...

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