Aging & Longevity

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White matter (WM) is a key substrate for interregional neural communication and cognitive function but the role of WM glucose metabolism in cognitive aging has been understudied. Using multimodal neuroimaging (MRI, FDG-PET, amyloid-PET) from 3142 participants (15,287 visits) across two studies, we examined the contribution of WM to cognition and identified divergent WM signatures. Higher glucose metabolism in expected WM (EWM; corpus callosum and cingulum) was associated with better cognition,...

Mesenchymal stem cells (MSCs) in bone marrow (BM) play a role in the development of BM adipose tissue (BMAT). Here, we propose ways to restock the BM-MSC niche to meet the needs of BMAT in ageing, including the activation of pluripotent precursor cells, the breakdown of BM-MSC grafts and the mobilisation of extramedullary MSCs. It can be exploited to understand the BM-MSC-adipocyte axis in ageing and better target anti-ageing interventions.

Age-associated hematopoietic stem cell (HSC) dysfunction is accompanied by dramatic transcription changes, but it remains unclear whether specific transcripts could orchestrate these HSC aging phenotypes. Here, we perform epigenetic profiling in male mice to investigate the regulatory mechanisms underlying the HSC aging transcriptome and screen for potential aging driver genes. We identify a looping structure formed between part of the Btaf1 gene and the whole Ide gene in old HSCs which is...

Senescent cells contribute to degenerative processes in multiple tissues, including the retina. In the retinal pigment epithelium (RPE), their accumulation is closely associated with retinal aging and disease progression. Eliminating senescent RPE cells has shown therapeutic potential, but conventional senolytics often lack the specificity required to spare non-senescent cells, raising safety concerns. To overcome this, we performed integrated transcriptomic analyses of male mouse-derived RPE...

The biological feasibility of human rejuvenation remains a subject of intense debate, yet answering this question is critical for guiding research strategies. Should aging research focus only on reversing aging in older individuals, or pausing its progression at mid-ages, be more accessible? Here, we attempt to address this question with evolutionary biology. Rejuvenation occurs in a few species, and, paradoxically, is typically induced by stress but not used under optimal conditions. Using...

The thymus is essential for establishing T cell diversity early in life, but undergoes profound involution with age and has therefore traditionally been regarded as largely nonfunctional in adults^(1,2). Here we propose that preserving thymic functionality is integral to adult health and longevity. We developed a deep learning framework to quantify thymic health from routine radiographic images and evaluated its association with longevity and risk of major age-associated diseases in two large...

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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...