Aging & Longevity

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...

Collagen, a central component of the extracellular matrix (ECM), precisely regulates tissue mechanical properties and biological functions through hierarchical assembly, playing a vital role in maintaining homeostasis. However, the molecular mechanism of assembly remains poorly understood, limiting insights into tissue remodeling, aging, and ECM-related diseases. Here, we employ time-resolved cryo-electron microscopy to resolve two critical hierarchical intermediates in fibrillar collagen...

Reactivating dead alkali metal is an effective strategy for extending the lifespan of alkali metal batteries. Until now, relevant works are mainly concentrated in lithium batteries, however, the reactivation of dead Na remains a mystery. Herein, dead Na reactivation is realized by a reverse-pulse-interspersed charging strategy. Transient large reverse currents are incorporated into the battery charging protocol, during which dead Na can be reactivated by the dielectrophoresis effect. Different...

The benefit of early diagnosis and treatment has been demonstrated in animal models of several lysosomal storage diseases. In a clinical setting, however, diagnoses are often not made until after patients become symptomatic. The lysosomal storage disease alpha-mannosidosis is caused by a genetic deficiency of lysosomal alpha-mannosidase, leading to the widespread presence of storage lesions throughout the brain and other tissues. In a feline model of alpha-mannosidosis, we previously...

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Methionine restriction has emerged as a promising strategy for extending lifespan and enhancing cancer therapy. LAT4, an amino acid transporter encoded by SLC43A2, is frequently overexpressed in multiple cancers and critically contributes to systemic methionine accumulation. However, the structural basis of LAT4 function remains poorly understood, and no effective inhibitors have been developed to date. In this study, we present high-resolution cryo-electron microscopy structures of LAT4 and the...

Photobiomodulation (PBM) is a non-invasive strategy to enhance cognitive function, yet the effects of stimulation frequency remain unclear. We applied pulsed 810 nm PBM at 5 Hz or 40 Hz to the frontal cortex of adult rats, and 40 Hz PBM to aged rats. In young adults, both stimulation frequencies enhanced cognitive flexibility, and in aged rats 40 Hz PBM improved learning speed. In terms of brain changes, we studied cytochrome c oxidase (CCO) activity, c-Fos expression and protein levels. We...