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Questions about the culprit virus and its route of spread remain as health officials make plans for stranded passengers

Levodopa-induced dyskinesia (LID) is a debilitating complication of symptomatic therapy in Parkinson's disease. Although there is compelling evidence that striatal pathophysiology is a major driver of LID, the specific circuit mechanisms governing its expression remain obscure. To address this gap, molecular, cellular, and behavioral strategies were used to interrogate circuits in a mouse model of LID. These studies revealed that LID induction led to an upregulation of GluN2B-containing...

Microplastics (MPs), defined as plastic fragments less than 5 mm in diameter, are ubiquitous in the environment. As an emerging environmental pollutant, MPs can infiltrate the human body through multiple pathways, including inhalation, ingestion, dermal contact and bloodborne transmission.Correspondingly, MPs, which can penetrate the blood-brain barrier and enter the central nervous system (CNS), have been linked to the development of neurodegenerative diseases (NDs).In this review, we provide a...

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,...

Pathological accumulation of toxic SNCA species and loss of E3-ligase function of PRKN are two key features observed in Parkinson disease (PD). Here, we established the contribution of an E3-ligase-independent transcriptional function of PRKN in SNCA regulation. PRKN depletion decreased SNCA and GBA1 (glucosylceramidase beta 1) mRNA levels and reduced CMA-driven degradation of SNCA, thereby triggering the accumulation of its phosphorylated aggregation-prone toxic species. We established that...

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...