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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,...

Alzheimer's Disease (AD) is a neurodegenerative condition affecting millions worldwide. Defining early pathobiological events remains challenging, in part due to inaccessibility of neural tissue. Because olfactory neurons are accessible, and olfactory loss is prevalent in AD, we evaluated olfactory brush biopsies from controls, individuals with cerebrospinal fluid (CSF) biomarker-confirmed AD, and cognitively typical individuals whose positive CSF biomarkers signal a pre-clinical AD stage. Here...

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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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Find explains how volcanic ash plumes spark lightning and why dust in grain silos can explode

Tiny capsules can deliver healthy organelles into animals with Parkinson’s-like and other mitochondria-linked disorders

Hyperphosphorylated Tau aggregates are a central pathological hallmark of Alzheimer's disease (AD), yet no approved therapy directly targets this process. mRNA therapeutics provide a transient and non-viral option but are limited by the blood-brain barrier (BBB). TRIM11 is an ATP-independent disaggregase that dissolves pathological Tau fibrils and promotes proteasomal clearance. Here, a ligand-free lipid nanoparticle (PLNP) is developed with zwitterionic, acetylcholine-mimetic...

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...