Aging & Longevity

Heat hormesis describes the beneficial adaptations resulting from transient exposure to mild heat stress, which enhances stress resilience and promotes healthy aging. While heat hormesis is widely observed, much remains to be learned about its molecular basis. This study bridges a critical knowledge gap through a comprehensive multiomic analysis, providing key insights into the transcriptomic and chromatin accessibility landscapes throughout a heat hormesis regimen in Caenorhabditis elegans. We...

Aging is a major risk factor for breast cancer, yet how it shapes tumor development, molecular phenotype, and immune evasion remains incompletely understood. Deciphering how aging influences cancer evolution is critical for improving risk assessment, prevention, and treatment. Here, using a N-nitroso-N-methylurea (NMU)-induced rat mammary tumor model that recapitulates key features of human breast cancer, we integrated bulk and single-cell transcriptomics, whole-exome sequencing, and...

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CONCLUSIONS: Controlling body weight and encouraging older adults to engage in physical activities that enhance handgrip strength can reduce the risk of dynapenia. Therefore, promoting self-care behaviors to reduce the adverse outcomes of dynapenia is crucial for enhancing healthy life in older populations.

INTRODUCTION: Mechanisms underlying age-related weakness are not fully understood, with neuronal mechanisms recently gaining attention. Despite studies on excitatory and inhibitory inputs, conflicting findings on α-motoneuron intrinsic excitability and PIC changes highlight a major gap in explaining age-related strength decline.

Changes in brain [NADPH]/[NADP^(+)] and [NAD^(+)]/[NADH] may contribute to aging. Anti-aging dietary restriction (DR) and intermittent fasting (IF) alter redox states that may contribute to their longevity effects. Pyruvate/lactate and acetoacetate/beta-hydroxybutyrate are indicators of the cytoplasmic and mitochondrial [NAD^(+)]/[NADH], respectively, while the malate/pyruvate and isocitrate/alpha-ketoglutarate are indicators of the cytoplasmic [NADPH]/[NADP^(+)]. Using these metabolite-pair...

Most diseases are not caused by large-effect single factors but by the cumulative impact of small, context-dependent perturbations arising from genetic variants, personal behavior, or environmental exposures, a phenomenon we term the "long tail" of biology. Early disease signals often differ from late-stage biomarkers and evolve across demographic, lifestyle, and environmental contexts. Shifting medicine from reactive treatment to proactive health requires detecting and interpreting these...

Blood factors transfer the benefits of exercise to the aged brain independent of physical activity. Here, we show that the liver-derived exercise factor (exerkine) glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (GPLD1), a GPI-degrading enzyme, reverses aging- and Alzheimer's-related memory loss by targeting the brain vasculature. GPLD1 has the potential to cleave over 100 putative GPI-anchored proteins, necessitating the identification of downstream targets that mediate cognitive...

Insulating sheaths of myelin accelerate neuronal communication in the mammalian brain. Oligodendrocytes that produce myelin are generated throughout life to gradually increase myelin coverage, but these dynamics have not been defined brain-wide across the lifespan. We developed a cellular mapping pipeline involving tissue clearing, lightsheet microscopy, and AI-assisted analysis to identify the precise location of millions of oligodendrocytes and assess regional myelin density in the mouse...

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CONCLUSIONS: The LTC Data Cooperative offers novel EHR data capturing clinical measures not available in the Minimum Data Set or claims data on a SNF resident population that is comparable to the national population. Studies using these data can generate evidence to inform and improve clinical care and outcomes for older adults in the SNF setting.

Mixed-matrix membranes (MMMs) with high chain packing density by incorporating soluble macrocycle compounds represent a promising class of materials for gas separation. However, achieving the ultra-high selectivity (He/CH(4) > 1000) for helium extraction from natural gas with ultra-low helium content remains a formidable challenge, especially for Matrimid membranes, which are commercially available but exhibit relatively low permeability and moderate selectivity. Herein, the cyclic Cyclen with...

Aging is accompanied by progressive impairment of neurovascular coupling (NVC), the mechanism that matches local cerebral blood flow to neuronal activity, contributing to cognitive decline and the development of vascular cognitive impairment and dementia. Exposure to a young systemic milieu through heterochronic parabiosis has been shown to restore NVC in aged mice, suggesting that circulating factors can rejuvenate cerebrovascular function. Yet, the molecular mediators responsible for this...

Subjective and objective markers are important in describing healthy aging, yet little is known about their relationships. This study analysed the time-dependent association of dehydroepiandrosterone sulfate (DHEAS) with subjective health. At baseline, DHEAS was measured in participants aged 45-83 randomly selected from the general population. Subjective mental and physical health were assessed using the 12-item Short Form (SF-12) questionnaire at baseline and two follow-ups. In sex-specific...

Dietary restriction may extend lifespan by improving late-life gut health. Because micronutrients mediate the effects of macronutrient ratios on longevity, we examined how cholesterol limitation affects gut health in female Drosophila melanogaster. Low-cholesterol diets increased intestinal permeability and reduced lifespan, however, not all flies lost barrier function before dying. This indicates gut dysfunction is either a marker of ageing, or contributes to death, but predominantly during...

Alzheimer's disease (AD) is an irreversible neurodegenerative disorder whose progression is closely associated with time. However, most diagnostic models are based on single time-point data, overlooking longitudinal disease characteristics. Structural magnetic resonance imaging (sMRI) has been widely utilized in the study of AD. To address the need for multi-time series analysis in longitudinal AD research and the integration of features from different brain tissues, we propose a Multi-Branch...

Visceral adipose tissue (VAT) is increasingly recognized as a metabolically active organ that contributes to systemic metabolic dysfunction and aging. Accumulation of VAT is thought not merely to be a biomarker of but also a causal contributor to impaired metabolic health and reduced lifespan. In this Review, we summarize evidence from both animal and human studies to evaluate whether this causal relationship truly holds. Our assessment indicates that VAT is not inherently harmful; rather, its...

Oxidative stress contributes to age-related musculoskeletal decline, partly through disruption of glutathione-dependent redox homeostasis. Although creatine and β-hydroxy-β-methylbutyrate (HMB) have been individually linked to antioxidant and cytoprotective effects, their combined influence on systemic redox balance in older adults remains insufficiently characterized.To examine the effects of creatine plus HMB supplementation on oxidative stress biomarkers and composite redox indices, and to...

Blood levels of neurofilament light chain (NfL) increase with age in healthy humans and have been shown to predict all-cause human mortality. To determine whether this relationship is conserved across species, we analyzed NfL in the blood of various animals. We observed age-related increases in NfL levels comparable to those seen in humans in mice, cats, dogs and horses. Longitudinal analysis of NfL trajectories in aged mice demonstrated that a faster rate of NfL increase predicts mortality....

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