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The GHK-Cu delays aging in Caenorhabditis elegans via coordinated regulation of mitochondrial function and activation of DAF-16/SKN-1 pathways

16 hours 23 minutes ago
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...
Huijun Wen

A <em>Caenorhabditis elegans</em> spatiotemporal proximity atlas reveals the MAPK p38 as a generator of phenotypic plasticity in vivo

16 hours 23 minutes ago
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,...
Wang Yuan

PRKN/parkin-mediated control of SNCA (synuclein alpha) and chaperone-mediated autophagy are defective in cellular, mice models and Parkinson disease-affected brains

16 hours 23 minutes ago
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...
Lígia Ramos Dos Santos

Aged Gut Microbiota Induces Mucosal Transcriptional Dysregulation, Impairing Immune Surveillance

16 hours 23 minutes ago
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...
Fang Wu

From "Passive Supplementation" to "Active Repair": Melatonin Reshapes the Treatment Paradigm for Late-Onset Hypogonadism by Targeting Leydig Cell Senescence

16 hours 23 minutes ago
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...
Hui Wu

Social Connectedness and Cognitive Function in Later Life: GrimAge as an Epigenetic Mediating Pathway

16 hours 23 minutes ago
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...
Layla Katharine Santana

Learning patient-specific spatial biomarker dynamics via operator learning for Alzheimer's disease progression

1 day 16 hours ago
Alzheimer's disease (AD) is a complex, multifactorial neurodegenerative disorder with substantial heterogeneity in progression and treatment response. Despite recent therapeutic advances, predictive models capable of accurately forecasting individualized future biomarker states remain limited. Here, we present a machine learning-based operator learning framework for personalized modeling of AD progression, integrating longitudinal multimodal imaging, biomarker, and clinical data. Unlike...
Jindong Wang

Metformin improves cardiac stress tolerance and mitochondrial function during early aging

1 day 16 hours ago
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...
Qun Chen