Aging & Longevity

CONCLUSION: These findings reveal a novel pulse-derived harmonic signature as a biomarker for prefrailty, indicating that subtle arterial functional alterations detectable via spectral analysis are associated with early physical vulnerability and may help bridge vascular pathology with geriatric decline. The discriminative performance (AUC = 0.70) is competitive with existing tools, while the 1-minute, noninvasive protocol establishes a favorable balance between accuracy and clinical...

CONCLUSIONS: Our study identifies CISD2 and MST1 as high-confidence proteins implicated in frailty pathogenesis through brain and plasma mechanisms, respectively. These findings provide crucial molecular insights into aging and highlight promising targets for therapeutic intervention to mitigate frailty.

CONCLUSIONS: Blood neurodegeneration biomarkers show complex associations with cognition that involve direct and physical performance-related pathways. Our findings suggest that physical performance may serve as an early marker and therapeutic target in neurodegenerative aging, particularly in vulnerable populations, though longitudinal studies are needed to establish temporal relationships.

Aging is a complex, multifactorial process, influencing disease risk and overall health. While chronological age (CA) is widely used in clinical practice, it fails to capture individual aging trajectories. Current approaches to estimate biological age (BA) often focus on single organs or predefined clinical biomarkers, limiting comprehensive assessment. We introduce a novel, purely imaging-driven deep learning framework for organ-specific BA estimation across seven organ systems. Our...

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...