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Caloric restriction (CR) provides anti-aging benefits but has also been reported to be associated with reduced immune function, and how hematopoietic stem cells (HSCs) potentially contribute to this decline remains unclear. Using lifelong and short-term CR in male mice, we found reducing the energy supply decreases total white blood cell production and shifts hematopoiesis towards myeloid and thrombo-erythroid lineages, prioritizing cells essential for survival (red blood cells, platelets,...

Mutations in genes encoding mitochondrial proteins are increasingly recognized as a major cause of neurodegenerative disorders, owing to the role of mitochondria in neuronal energy metabolism and signaling. Here, we investigate MTNAP1 (mitochondrial nucleoid-associated protein 1) as a novel gene associated with an autosomal recessive neurodevelopmental disorder characterized by progressive cerebral and cerebellar atrophy. Three affected probands from two unrelated families presented with global...

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Experimental models such as heterochronic parabiosis and heterochronic plasma transfer have profoundly advanced our understanding of systemic aging, demonstrating that circulating factors can influence brain, vascular, and immune aging through cell nonautonomous mechanisms. These preclinical models have revealed that both pro-geronic and anti-geronic signals in blood can modulate neuroinflammation, neurovascular health, and cognitive resilience. However, despite their experimental promise, the...

Tauopathies are neurodegenerative diseases marked by pathological tau aggregation. While disease-specific folds of insoluble tau filaments have been established, it remains unclear whether the smaller, earlier species also differ across tauopathies. Here, we characterize these small tau aggregates from postmortem brain of individuals with Alzheimer's disease (AD), progressive supranuclear palsy (PSP), corticobasal degeneration, Pick's disease, and healthy controls. Using two complementary...

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...