Aging & Longevity

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...

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.

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...

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,...

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...

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...

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...

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Adrenergic signalling is heavily implicated in human age-related disease and yet the potential for this neuroendocrine signalling pathway to modulate ageing has received little attention. Here, we use Drosophila melanogaster to test if adrenergic-like signalling can promote longevity by manipulating tyramine (TA) or octopamine (OA), the invertebrate equivalents of adrenergic hormones. Increased neuronal synthesis of TA boosts health and longevity in both sexes, whereas OA is marginally...

CONCLUSION: The present study identifies Siah-1 as a novel mediator linking hypoxic signaling to SKN-1-dependent transcriptional programs, providing insights into conserved mechanisms of stress adaptation and aging. This work underscores the importance of ubiquitin-mediated regulatory nodes in coordinating longevity pathways under environmental stressors.

The integrated stress response (ISR) is essential for cellular homeostasis and cognitive function. We investigated how persistent ISR activation affects cognitive performance by studying the PPP1R15B^(R658C) genetic variant associated with intellectual disability. To model this condition, we generated a mouse line with the pathogenic allele inserted. This variant destabilized the PPP1R15B•PP1 phosphatase complex, causing persistent ISR activation, impaired protein synthesis, and long-term memory...

Biocompatible integration of synthetic materials with living tissue remains a major challenge for bioelectronics. In this case, substrate-free conducting polymer (CP) interfaces could help bridge this gap. We report in vivo assembly of n-doped poly(benzodifurandione) (n-PBDF) using whole blood-catalyzed polymerization in awake zebrafish and mice. This approach leverages endogenous catalysts, specifically hemoproteins, to form stable, thermally and ionically sensitive CP networks, ensuring...

Extracellular adenosine (e-Ado) is a critical signaling molecule, yet its origin beyond energy stress and inflammation is underexplored. Herein, we propose that Ado is ubiquitously generated in the S-adenosylmethionine transmethylation pathway and integrate this source with the concept of cellular privilege in nutrient acquisition. In this model, less privileged cells convert Ado to adenosine monophosphate (AMP) under nutrient scarcity, activating AMP-activated protein kinase, while privileged...

Aging reshapes T cell immunity, as evidenced by eroding naive diversity and remodeled memory hierarchies. This generates an experienced yet constrained repertoire, with weakened protection against novel infections and malignancies and blunted vaccine responsiveness. However, the pace and extent of decline vary widely between individuals. Such heterogeneity signals a recalibration of immune priorities that favors persistence over plasticity of memory T cells. Here, we discuss how aging shapes...

Cancer immunotherapy has markedly improved patient outcomes, particularly when combined with conventional treatments such as chemotherapy, radiotherapy, and targeted therapy. Following these therapies, however, a subset of cancer cells can enter a senescent state, ceasing proliferation while remaining metabolically active and persistent within tissues. Such therapy-induced senescent cancer cells (TISCCs) significantly influence antitumor immune responses. TISCCs can enhance tumor immunogenicity...