Aging & Longevity

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Treatment decisions in IDH-mutant oligodendrogliomas are shaped by tumor aggressiveness, underscoring the need for objective grading of these malignant brain tumors. We collect 302 primary and recurrent resections from oligodendrogliomas and perform Ki-67 staining, proteomics, and DNA methylation profiling. During tumor progression, DNA methylation of oligodendrogliomas changes along a continuum. This continuum is linked to increased epigenetic aging, methylation of transcription factors and...

Aging is a multifactorial process characterized by a gradual decline in function, increased susceptibility to diseases, and diminished regenerative capacity. As the primary refractive structure and barrier of the eye, the cornea undergoes significant structural and functional changes during aging, making individuals more prone to various ocular surface diseases. Key age-related corneal changes include epithelial thinning, stromal remodeling with increased collagen cross-linking, endothelial cell...

CONCLUSIONS: WWI was significantly associated with fall risk and severity in older adults. Further prospective studies are essential to validate its predictive value in fall risk stratification and prevention.

Exercise training improves the age-induced decline in oxidative metabolic capacity in cardiac mitochondria. Nuclear respiratory factor-1 (NRF-1) signaling via peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) regulates genes encoding mitochondrial oxidative metabolic enzymes. However, the effects of aging and subsequent exercise training on fatty acid (FA) metabolism-related gene expression via the myocardial PGC-1α-NRF-1 pathway, and the relevance of these changes to...

During aging, decreased intestinal barrier function and its ability to synthesize metabolites are closely associated with various age-related diseases. However, the mechanism by which impaired intestinal synthesis contributes to gut-liver axis aging remains unclear. This study reveals that aging induces a mitochondrial energy crisis and defective membrane localization of ABCA1, significantly inhibiting the biosynthesis of high-density lipoprotein 3 (HDL3) in the intestine. Exogenous...

Hyperparathyroidism is an endocrine disorder linked to vitamin D deficiency. Reduced vitamin D receptor (VDR) activity promotes parathyroid hormone (PTH) hypersecretion by increasing heterodimerization of the type B γ-aminobutyric acid receptor 1 (GABA(B1)R) with the extracellular Ca^(2+)-sensing receptor (CaSR) in parathyroid cells; however, endogenous activators of the heterodimers are unknown. We uncovered increased expression of amyloid-β peptide cleaved from the amyloid-β precursor protein...

The function of innate immune sensors is intricately shaped by their spatial distribution within cells. cGAS (cyclic GMP-AMP synthase), a key cytosolic DNA sensor, illustrates this principle through its unexpected localisation to diverse organelles-including the nucleus, micronuclei, mitochondria, and plasma membrane. In these compartments, cGAS assumes distinct regulatory states and executes specialised functions. For instance, chromatin-bound nuclear cGAS remains inactive under homeostasis but...

Integrating the diagnostic and therapeutic functions of drugs poses challenges due to specific structural design requirements. However, the trial-and-error dilemma in performance-driven structural evolution of nanomaterials is unsatisfactory. Here, we propose a strategy using graphene quantum dots with sp²-sp³ hybridized carbon frameworks for visualized, intelligent targeted clearance of metabolically reprogrammed senescent cells. We establish a structure-activity relationship between the...

Anode-free lithium metal batteries (AFLMBs), which are manufactured without anode active material, offer great potential for high-energy-density, low-cost energy storage. However, AFLMBs face a long-standing challenge of short lifespan due to the harsh conditions of lacking excess Li-resource and an anode host^(1-8). This issue is associated with uneven Li deposition/dissolution, rooted in the micro-heterogeneity and mechanical fragility of solid electrolyte interphase (SEI)⁹. Here we report a...

Modern biology increasingly relies on complex, high-dimensional datasets such as single-cell RNA sequencing (scRNA-seq), which present a vast space of potential hypotheses. Systematically exploring this space is often impractical, as scRNA-seq analyses are time-consuming and require substantial computational and domain expertise. To address this challenge, we introduce CellVoyager, an AI agent built on large language models that autonomously generates and implements scRNA-seq analyses within a...

Dental collagen, a protein subject to essentially zero turnover, is highly susceptible to the accumulation of advanced glycation end-products (AGEs) due to elevated blood glucose in type 2 diabetes mellitus (T2DM). Progressive loss of collagen's structural stability likely increases the risk of tooth decay and fracture complicating the proper fixation of dental restorations. Our study aimed at investigating the structural and mechanical alterations in T2DM-affected teeth by measuring the...

CONCLUSIONS: Like the broader frailty literature, emerging AI tools lack a consistent definition of frailty, leading to design and implementation inconsistencies. The absence of knowledge user involvement may further limit the clinical relevance and equity of these technologies.

The Interventions Testing Program (ITP) evaluated eleven compounds in genetically heterogeneous UM-HET3 mice to assess their potential to extend lifespan. These interventions included both novel agents and previously tested compounds administered at novel doses or starting ages. Despite prior evidence suggesting lifespan benefits of these proposed interventions in other models or under different conditions, none of the tested compounds significantly increased lifespan in male or female mice....

The human skin microbiome is essential for health and is shaped by both host and environmental factors. To establish a nationwide baseline, we profile the skin microbiome of 1,029 Chinese individuals across three body sites (hand, axilla, and foot), four geographic regions, and four ethnic groups using 16S rRNA gene sequencing. Within each skin site, we identify two cutotypes, one of which is consistently dominated by Staphylococcus. Microbial diversity and community composition vary across body...

Aging is a primary risk factor for disease progression in multiple sclerosis (MS). Because of this, treatments that can reduce the consequences of molecular aging, like senescence, have been proposed as a strategy to address disease progression. However, the effects of senolytics, a class of drugs which selectively ablate senescent cells, on the central nervous system are largely unknown. Here, we examined the effects of senolytic treatment on myelination and oligodendrocyte function in vivo...

Proteomics enables the systematic elucidation of biological mechanisms underlying frailty. Through a large proteome-wide association study of 2,911 plasma proteins from 50,506 UK Biobank participants, we identified 1,339 proteins significantly associated with frailty, highlighting collagen-containing extracellular matrix and vesicle lumen pathways. Replication in the TwinGene study confirmed partial but consistent associations. Mendelian randomization analyses identified five potentially causal...

We present TLPath, a deep learning framework that predicts bulk-tissue telomere length from tissue morphology extracted from routine histopathology images. The central thesis of TLPath is that telomere length can be determined from tissue morphology. Trained on >5,000 whole-slide images across 919 individuals and 18 organs, TLPath discovers that extracted morphological features naturally separate young, middle-aged, and elderly individuals, demonstrating that aging causes architectural changes...

Perovskite solar cells tend to degrade much faster under day-night cycling conditions. One key reason lies in the periodic strain in perovskite film under cycling mode due to its soft crystal lattice nature. Here, we propose a dynamic reversible crosslinking strategy by introducing disulfide-mediated cross-linkable additive of 2-methacryloyloxyethyl-thioctate. Combining with carbon-carbon double bond, 2-methacryloyloxyethyl-thioctate crosslinks at grain boundaries at high temperature through...