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Alzheimer's disease (AD) is a neurodegenerative disorder characterized by progressive cognitive decline, yet its epigenetic underpinnings remain elusive. Here, we generate and integrate single-cell epigenomic and transcriptomic profiles of 3.5 million cells from 384 postmortem brain samples across 6 regions in 111 AD and control individuals. We identify over 1 million candidate cis-regulatory elements (cCREs), organized into 123 regulatory modules across 67 cell subtypes. We define large-scale...

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Emerging gene-editing technologies, such as the CRISPR system, represent a potential pathway for precision medicine targeting the genetic and molecular causes of diseases. Second-generation CRISPR technologies, including base editing, prime editing, and engineered Cas variants, have improved fidelity and offer alternative strategies for precise gene correction, transcriptional repression or activation, and modulation of pathological pathways in neurodegeneration. These tools can correct...

Personality changes are a clinical criterion for dementia diagnosis, yet their progression across disease stages remains unclear. This systematic review and meta-analyses examined change in the five major personality traits across the preclinical, transitional, and clinical dementia stages. We conducted pre-registered searches of three databases from their inception to November 2024. The standardized mean difference (SMD) with 95 % CIs were combined in random-effects meta-analyses. Prospective...

Skin ageing is a multifaceted process influenced by both intrinsic genetic factors and extrinsic environmental exposures. This review explores the genetic variants and molecular mechanisms underlying skin ageing phenotypes, while identifying gaps in current research to inform future studies. A systematic search of the Scopus and Web of Science databases was conducted, with articles screened based on criteria including a focus on human genetic association studies and indexing in either Scopus or...

Age-related declines in neuronal bioenergetic levels may limit vesicular trafficking and autophagic clearance of damaged organelles and proteins. Age-related ATP depletion would impact cognition dependent on ionic homeostasis, but limits on proteostasis powered by GTP are less clear. We used neurons isolated from aged 3xTg-AD Alzheimer's model mice and a novel genetically encoded fluorescent GTP sensor (GEVAL) to evaluate live GTP levels in situ. We report an age-dependent reduction in...

Human brains undergo considerable morphologic variation with age, a primary risk factor for neurodegenerative disorders. While aging often causes neurocognitive decline, its governing biological mechanisms remain unclear. These age-related brain microstructural changes may be quantified by advanced diffusion MRI (dMRI) with tissue-specific compartment modeling approach. This longitudinal study investigates age-related differences in hippocampal subfields vulnerable to early stages of Alzheimer's...

CONCLUSIONS: The finding that patients with insomnia exhibited shorter telomeres than those with RLS and OSAS suggests that insomnia may present a higher risk for age-related diseases and accelerated aging processes.

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During prostate aging collagen-IV is modified by advanced glycation end-products, inducing crosslinking of the basement membrane surrounding glandular acini. Basement membrane stiffness sensed by Endo180 disrupts its suppressor complex with CD147, triggering epithelial-to-mesenchymal transition and limiting survival in prostate cancer patients. Here we report basement membrane stiffness and Endo180 cooperate in rewiring epithelia for mitochondrial oxidative phosphorylation (OXPHOS) and growth...

The survival of antibody-secreting plasma cells is essential for long-lasting humoral immunity. BCMA is proposed to promote APRIL-mediated survival signals. However, extensive shedding of murine BCMA raises doubts about its role as a signaling receptor. To unequivocally establish BCMA's function in plasma cell survival, we generate two BCMA-deficient mouse lines and examine antigen-specific plasma cells post-immunization. Contrary to previous reports, both BCMA-deficient mouse lines have...

The C. elegans-Orsay virus pathosystem provides a powerful model for investigating the mechanisms that govern viral infection and immunity. Here, we focus on two key aspects of this interaction: the impact of lifelong latent infections and the dynamics of superinfection. By tracking the course of a lifelong infection, we demonstrate that the infection remains latent, with animals maintaining control over viral replication for most of their lifespan. Furthermore, we show that animals previously...

Accumulating evidence suggests that mitogenic signaling during cell cycle arrest can lead to severe cytotoxic outcomes, such as senescence, though the underlying mechanisms remain poorly understood. Here, we explored the link between cell cycle dynamics and the formation of PML-nuclear bodies (PML-NBs), intranuclear structures known to mediate cellular stress responses. Our findings demonstrate that PML-NBs increase their number during interphase arrest. Moreover, the activation of mitogenic ERK...

Plan to revamp research and merge environment and energy ministries sparks concern

The iPsych project, which investigates the genetics of psychiatric disorders, has sent 140,000 opt-out notices amid backlash

Cognitive aging is associated with increased prefrontal cortex (PFC) activity, often interpreted as either a compensatory mechanism or a sign of neural inefficiency. In the context of speech-in-noise perception, it remains unclear whether this increase supports or impairs performance, as findings across studies are mixed. This study investigated age-related differences in PFC activity during sentence comprehension in noise using functional near-infrared spectroscopy. Fifty-seven participants (22...

Combating aging has become a central challenge in the life sciences, and myocardial aging, as a fundamental pathological process underlying the development and progression of various cardiovascular diseases, has become a key area in anti-aging research. In recent years, lactylation and methylation, two metabolism-dependent epigenetic modifications, have garnered increasing attention in the context of myocardial aging. Lactylation, mediated by lactate accumulation due to metabolic dysregulation,...

CONCLUSION: All visceral fat accumulation indicators were positively associated with sarcopenia risk and WWI identified as the most important predictor. The ML model achieved high predictive accuracy, highlighting the role of visceral fat accumulation in sarcopenia risk and healthy aging promotion.

Epigenetic drift refers to the gradual and stochastic accumulation of epigenetic changes, such as DNA methylation variability, with advancing age. Although increasingly recognized for its potential role in aging biology, its extent, biological significance, and population specificity remain insufficiently characterized. Here, we present the first comprehensive epigenome-wide drift study (EWDS) in a large Chinese cohort (n = 3,538), with replication in two independent Chinese (total n = 1,467)...

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