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Psilocybin and human longevity

2 weeks 1 day ago
Psilocybin extends lifespan in aged mice, and this has prompted extensive media speculation about possible human longevity benefits. We examined mortality among prominent psychedelic personalities, researchers, and advocates who claimed psychedelic use (n = 11) and compared them with cancer (n = 12) and aging researchers (n = 5). All groups exceeded population life expectancy, reflecting the effect of socioeconomic advantage on lifespan, but psychedelic personalities did not outlive cancer and...
Leonard Lerer

Dissecting the boundary of quiescence and activation of murine melanocyte stem cells in the hair follicle niche

2 weeks 1 day ago
Melanocyte stem cells (McSCs) are a crucial melanocyte reservoir within the hair follicle niche. This review provides an overview of the processes for McSC quiescence and activation. Because McSCs closely interact with hair follicle stem cells, we have focused on this interaction. Given the high prevalence of hair graying, the McSC system serves as a model for cellular aging. Here, we highlight current research on the mechanisms of hair graying.
Tatsuya Ogawa

Plasma Proteomic Profiling of Young and Older Adults Identifies Candidate Biomarkers of Biological Aging at the Intersection of Age and Disease

2 weeks 1 day ago
Aging and chronic diseases intersect at the level of biological aging mechanisms, where age-related molecular and cellular changes contribute to the development of diverse pathologies. Biomarkers of biological aging could help predict and track the progression of chronic diseases and evaluate the effectiveness of interventions aimed at promoting healthy aging. Here, we aimed to identify biomarkers reflecting biological aging by analyzing protein signatures shared between older age and elevated...
Juliette Tavenier

The exposome of brain aging across 34 countries

2 weeks 1 day ago
The physical and social exposome affects human aging, and brain clocks may track its effects. However, most studies neglect multidomain exposures (physical, social and political) across diverse settings globally and their associations with brain aging. In this study, we characterized the associations between 73 country-level physical and social exposomal factors and multimodal brain age in 18,701 participants from 34 countries (healthy individuals and those with Alzheimer's disease,...
Agustina Legaz

The case for space as a model of accelerated aging

2 weeks 1 day ago
Aging is a complex biological and societal challenge, where modest advances can yield substantial clinical and economic benefits. While model organisms have uncovered key mechanisms of aging, their physiological relevance to humans remains limited. Astronauts offer a uniquely informative human model: despite being healthy and highly selected, they exhibit many hallmarks of aging and experience comparable declines in cardiovascular, musculoskeletal, cognitive and immune function-often on...
Max Manwaring-Mueller

Neuronal APOE4-induced early hippocampal network hyperexcitability in Alzheimer's disease pathogenesis

2 weeks 1 day ago
The full impact of APOE4 (apolipoprotein E4), the strongest genetic risk factor for Alzheimer's disease (AD), on neuronal and network function remains unclear, particularly during early preclinical stages of disease. Here we show that young APOE4 knockin (E4-KI) mice exhibit hippocampal region-specific network hyperexcitability that predicts later cognitive deficits. This early phenotype arises from cell-type-specific subpopulations of smaller, hyperexcitable neurons and is eliminated by...
Dennis R Tabuena

The longevity effects of reduced IGF-1 signaling depend on the stability of the mitochondrial genome

2 weeks 1 day ago
Suppression of insulin-like growth factor-1 (IGF-1) signaling extends mammalian life span and protects against a range of age-related diseases. Unexpectedly, we found that reduced IGF-1 signaling fails to extend the life span of mitochondrial mutator mice. Most of the longevity pathways that are normally initiated by IGF-1 suppression were either blocked or blunted in the mutator mice. These observations suggest that the prolongevity effects of IGF-1 suppression critically depend on the...
Sarah J Shemtov

RUVBL2 Regulates Microglia Metabolic Reprogramming to Mediate Stress Granules Aggregation Exacerbating Postoperative Delirium in Aged Mild Cognitive Impairment Rats

2 weeks 1 day ago
Postoperative delirium (POD) accelerates the transition from mild cognitive impairment (MCI) to Alzheimer's disease (AD) in elderly patients. Microglial metabolic reprogramming, a pivotal aspect of the immune-inflammatory response, modulates microglia-neuron interactions and postoperative cognitive function through microenvironmental alterations. Aberrant overexpression of RUVBL2 disrupts metabolic homeostasis, leading to stress granule (SG) aggregation and fibrosis. This study investigated the...
Lin Zhang

Deletion of SPI1 in microglia exacerbates amyloid pathology by impairing microglial response in Alzheimer's disease models

2 weeks 1 day ago
Recent human genetic studies have highlighted the potential role of microglial genes and their regulatory functions in the pathogenesis of Alzheimer's disease (AD). The transcription factor PU.1 (encoded by SPI1) is expressed mainly in microglia in the central nervous system and has been reported to be a genetic risk factor for AD. However, the role of microglial SPI1 in AD etiology is still poorly understood. Here, we demonstrate that the selective deletion of Spi1 in microglia exacerbates...
Byungwook Kim

Identifying maximally informative signal-aware representations of single-cell data using the information bottleneck

2 weeks 1 day ago
Rapid advancements in single-cell RNA sequencing (scRNA-seq) technologies revealed the richness of myriad attributes encompassing cell identity. However, the complexity of the data hinders tasks focusing on a specific biological signal. To address this challenge, we introduce bioIB, a framework based on the information bottleneck method, designed to extract an interpretable compressed representation of scRNA-seq data, optimally informative with respect to a specific biological signal, such as...
Serafima Dubnov