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Amyloid-β (Aβ) fibrils primarily composed of Aβ(1-40) and Aβ(1-42) form the core of senile plaques in Alzheimer's disease. Aβ(1-40) fibrils may exhibit significant polymorphism influenced by sample preparation conditions, complicating atomic resolution structural characterization. To establish a reliable structural baseline, we developed a protocol for expressing and purifying recombinant Aβ(1-40) that forms monomorphic fibrils under physiological conditions (pH 7.4). We present a...

Sleep deprivation (SD), together with inevitable stress inherent to conventional SD protocols, can induce oxidative stress and inflammation, thereby increasing the risk of premature death. However, the source and signaling pathways underlying reactive oxygen species (ROS) generation remain unclear. Here, we demonstrate that both mechanical and thermogenetic SD, along with possible stress induced by both protocols, lead to initial ROS accumulation in Drosophila gut subregions, including the...

Insufficient understanding of α-synuclein turnover mechanisms has impeded successful clinical translation for Parkinson's disease (PD). Here, we pinpointed cholesterol 25-hydroxylase (CH25H) as a pivotal regulator of α-synuclein degradation. Through bulk RNA sequencing of substantia nigra tissue from the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD, along with reanalysis of published datasets from induced pluripotent stem cell-derived astrocytes of patients with PD, we...

An established vascular network is a prerequisite to ensuring an optimal supply of oxygen and nutrients for sustaining developmental events and systemic function. Herein, we construct a time-resolved proteolipidomic atlas of the aorta across the human life cycle. trans-omics integration reveals that postnatal ganglioside GM3 accumulation is functionally coregulated with calcium homeostasis mediated by plasma membrane calcium-transporting ATPases (PMCAs). We then verify mechanistically in...

Extracellular matrix degradation is a fundamental pathological feature of osteoarthritis, while the roles of degraded matrix remain largely unknown. We previously showed that serum elastin fragments were a systemic aging driver. Here, we found that elastin fragments were upregulated in synovial fluid in dual-center osteoarthritis patients. Elastin fragments actively impaired joint tissue in mice and human explants. Mechanistically, a specific elastin motif containing...

Sleep deprivation (SD), together with inevitable stress inherent to conventional SD protocols, can induce oxidative stress and inflammation, thereby increasing the risk of premature death. However, the source and signaling pathways underlying reactive oxygen species (ROS) generation remain unclear. Here, we demonstrate that both mechanical and thermogenetic SD, along with possible stress induced by both protocols, lead to initial ROS accumulation in Drosophila gut subregions, including the...

Roman concrete structures have remained serviceable for nearly two millennia and are widely regarded as outstanding examples of durable ancient engineering. Existing literature attributes Roman concrete longevity to the pozzolanic reaction that occurs between reactive volcanic ashes and lime. While the pozzolanic reaction is of fundamental importance, we argue that carbonation over a long period of time also substantially enhances the durability and potential self-healing properties of concrete....

Autosomal monoallelic gene expression and asynchronous replication between alleles are established features of imprinted genes and genes regulated by allelic exclusion. Inactivation/Stability Centers (I/SCs) are recently described autosomal loci that exhibit epigenetic regulation of allelic expression and replication timing, with differences that can be comparable to those observed between the active and inactive X chromosomes . Here, we characterize >100 autosomal loci with allele-specific...

Cellular senescence has emerged as a central mechanism driving cutaneous aging, impaired regeneration, and numerous dermatologic pathologies. Initially evolved as a protective mechanism to prevent malignant transformation and facilitate wound repair, senescence becomes maladaptive when senescent cells persist. Senescent keratinocytes, fibroblasts, and melanocytes can secrete pro-inflammatory mediators and other factors, collectively termed the senescence-associated secretory phenotype (SASP),...

Sirtuin 6 (SIRT6) is a protein deacetylase and ribosyltransferase that is a vital hub for maintaining epigenetic homeostasis, regulating the transcriptome, and repairing DNA double stranded breaks (DSBs). Comprehensive proteomic profiling of the SIRT6 posttranslational landscape, however, remains elusive. The SIRT6 C-terminal domain contains multiple phosphorylation sites. We find that the presence and the use of these sites are strongly correlated with maximum lifespan across mammals....

Late-life depressive symptoms have been associated with structural brain changes and cognitive impairment, but prior studies have typically examined individual markers of brain aging in isolation. This study examined the associations between depressive symptoms and multiple markers of brain aging in a population-based cohort of community-dwelling older adults. Baseline data from 2,746 participants with complete data on depressive symptoms, neuroimaging measures, cognitive assessment, and...

Cognitive impairment is highly prevalent among patients with end-stage renal disease (ESRD), particularly those undergoing dialysis, and is associated with poor clinical outcomes and reduced quality of life. Emerging evidence suggests that Klotho, an anti-aging protein predominantly expressed in the kidney, plays a critical role in the pathophysiology of uremia-related cognitive dysfunction. This review summarizes current clinical and experimental evidence regarding Klotho deficiency in dialysis...

Scientists have discovered that creatine may strengthen one of the immune system's most important cancer-fighting pathways by energizing dendritic cells that activate killer T cells. The promising results could eventually help make immunotherapy more effective, but they have not yet been tested in human patients.

Intermittent fasting helped people lose as much weight as calorie restriction, but without the same feeling of constantly controlling their food intake. Researchers say that difference could make fasting a more sustainable option for people who struggle with traditional diets.