Aging & Longevity

Over the past decade, clonal hematopoiesis (CH) has gained substantial attention as a prevalent, age-associated phenomenon with major implications for hematologic malignancy, cardiovascular disease, and mortality. CH arises from the clonal expansion of hematopoietic stem cells and progenitor cells harboring somatic mutations, most commonly in genes implicated in leukemia. Beyond chronological aging, CH evolution is shaped by lifelong exposure to inflammatory, metabolic, and environmental...

From a cellular perspective, senescence has been considered a binary state, wherein cells are either senescent or not. This reductionist notion, often defined as irreversible growth arrest, has guided efforts to identify universal biomarkers and senolytics, but both have consistently eluded us. This outcome is not surprising, given that the biological nature of senescence may not be strictly irreversible; the accumulated evidence suggests that growth arrest can become unstable over time, with...

Aging is a complex biological process characterized by progressive functional decline and increased risk of chronic diseases. In recent years, DNA methylation-based epigenetic clocks have emerged as some of the most robust biomarkers for estimating biological age. Initial research clocks, such as those developed by Horvath and Hannum, provided highly accurate chronological age predictions. Subsequent models, including PhenoAge, GrimAge, and DunedinPACE, improved upon this by incorporating...

CONCLUSION: Different physical activity intensities were not significantly associated with resting-state functional connectivity of various brain networks in a sample of healthy older adults. This finding contrasts with the results of previous cross-sectional studies.

Stroke remains the second leading cause of death globally, yet traditional risk factors explain only 50-60 percent of cases. Emerging evidence indicates that lipid dysregulation is a central mechanism linking environmental exposures to cerebrovascular vulnerability. Aging, chronic inflammation, infections, diet, inactivity, stress, sleep disorders, and toxins are associated with disruption of lipid homeostasis through oxidative stress-induced lipid peroxidation, cytokine-mediated metabolic...

Mitochondrial dynamics play a critical role in the development of aging-related diseases such as type 2 diabetes mellitus. To investigate how mitochondrial dynamics influence cellular behavior in pancreatic beta-cells, we developed a rule-based, multi-level simulation model of insulin secretion. The pancreatic beta-cell model encompasses metabolic pathways (glycolysis and oxidative phosphorylation), compartmental processes (mitochondrial fusion and fission), and cellular processes (insulin...

Sepsis disproportionately affects older adults and children, two immunologically vulnerable extremes of age. Yet sepsis is superimposed on distinct baselines-immunosenescence in the elderly and immune immaturity in neonates and young children-leading to different pathways toward immune failure. This comparative narrative review synthesizes clinical and experimental evidence on age-specific and shared alterations in lymphocyte subsets in sepsis, including lymphopenia; CD4^(+) and CD8^(+) T cell...

In this prospective cohort study of 1545 participants aged 80 years and older from the China Hainan Centenarian Cohort Study, we investigated the independent and joint associations of modifiable risk factors and genetic predisposition with life expectancy. A weighted modifiable risk factor score (MRFS) based on 11 factors and a polygenic risk score (PRS) for longevity were constructed. A favorable modifiable risk factor profile (low MRFS) was associated with a 40.7% lower death risk (HR 0.593,...

Cancer-causing mutations have been identified primarily from positive selection signals in cancer genomes. However, positive selection is also a ubiquitous feature of normal tissue aging. Here we develop a statistical framework to disentangle selection in normal tissue and causation of carcinogenesis. By comparing cancer and normal tissue genomes, we estimate the effects of mutations on cancer risk in the blood, esophagus and colon. We determine that stronger cancer-causing mutations are...

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Cellular senescence is a multifaceted stress response marked by stable proliferative arrest and the secretion of diverse biologically active factors, collectively known as the senescence-associated secretory phenotype (SASP). The senescent phenotype is remarkably variable and subject to various regulatory influences. We previously demonstrated that mitochondrial dysfunction induced by diverse stimuli, including the loss of sirtuin 3 (SIRT3), leads to the hyperactivation of AMPK and p53,...

With an ageing population comes a growing burden of age-related cognitive decline. While evidence supports a relationship between higher diet quality and better cognitive outcomes, the association between ultra-processed foods (UPFs) and cognitive function remains underexplored. We examined this association using prospective data from the ASPirin in Reducing Events in the Elderly (ASPREE) study, a cohort of Australian adults aged 70 years and older. Dietary intake was assessed via a mail-based...

This study examined associations between diet quality, epigenetic age acceleration (EAA), and mortality in two U.S. cohorts: NHANES (n = 2158) and HRS (n = 1752), while accounting for demographic and socioeconomic (SES) determinants. Diet was evaluated as a potentially modifiable exposure within broader social and biological pathways. Participants were linked to the National Death Index. Cox proportional hazards models, additive Bayesian networks (ABN), generalized structural equation models...

Vascular aging, characterized by progressive structural and functional deterioration of the vasculature, serves as a critical pathophysiological nexus between chronological aging and cardiovascular disease (CVD). This study establishes a quantitative vascular age model to decode individualized vascular senescence patterns, thereby enabling early identification of accelerated aging phenotypes for targeted intervention. We collected physical examination records from 2009 to 2019 and a total of...

Aging is a complex biological process characterized by progressive functional decline across tissues and increased susceptibility to age-related diseases, with oxidative stress being a key contributing factor. Glycine-Histidine-Lysine (GHK), a naturally occurring tripeptide present in human plasma and urine, possesses potent antioxidant properties; however, its broader anti-aging potential remains inadequately explored. In this study, we employed the model organism Caenorhabditis elegans to...

Phenotypic plasticity, the ability to change diverse traits without altering genomic information, is fundamental for organismal adaptations to changing environments. The mitogen-activated protein kinase (MAPK) pathway plays a key role in cellular adaptations to changing environments. To analyze the contributions of the MAPK p38 and its interaction partners to phenotypic plasticity in an animal, we established an in vivo proximity labeling proteomics method called ContinuumID. With this method,...

Aging is associated with systemic immune remodeling and disease susceptibility, but its impact on intestinal mucosal immunity, particularly changes in M cells, remains largely unknown. This study aimed to investigate how aging alters intestinal mucosal immune phenotypes, specifically follicle-associated epithelial cells (FAE) and the gut microbiota, and to identify interconnected pathways that may be exploited to maintain intestinal immune function in the elderly. Using intestinal tissue from...

In the context of global population aging, public health challenges due to aging are garnering significant attention. Late-onset hypogonadism (LOH) is a common age-related condition in men characterized by progressively decreasing serum testosterone levels with age, manifesting as sexual dysfunction, reduced physical vigor, and psychological or neurological abnormalities. Testosterone is synthesized primarily in testicular Leydig cells (LCs), and LC senescence during aging is key for suppressing...

ObjectivesTo test whether epigenetic aging mediates associations between social connectedness and later cognitive function among U.S. older adults.MethodsUsing Health and Retirement Study data (N = 1,574; mean age = 68.5), we modeled 2014 social connectedness as a latent factor (participation, isolation, loneliness), assessed four DNA methylation clocks in 2016 (DNAmGrimAge, DunedinPoAm, DNAmPhenoAge, Zhang), and cognition in 2018. Survey-weighted regression-with-residuals mediation models...

Cardiac aging reduces stress resistance and increases the susceptibility to myocardial injury. Although cardiac dysfunction typically manifests in late-stage aging, the underlying process begins in middle age. Elevated endoplasmic reticulum (ER) stress is a key contributor to cardiac aging. We have shown that ER stress increases in middle-aged hearts and peaks in advanced age, while chronic metformin treatment reduces ER stress and improves mitochondrial function in late-aged hearts. This study...