Aging & Longevity

CONCLUSION: There was a downward trend in global ICH incidence from 1992 to 2021. Economically developed countries must remain vigilant against the rise in ICH cases due to aging. For males, primary prevention should target the younger adults, whereas for females, it should target aged population.

Age-related decline in intrinsic capacity (IC), defined as the sum of an individual's physical and mental capacities, is a cornerstone for promoting healthy aging by prioritizing maintenance of function over disease treatment. However, assessing IC is resource-intensive, and the molecular and cellular bases of its decline are poorly understood. Here we used the INSPIRE-T cohort (1,014 individuals aged 20-102 years) to construct the IC clock, a DNA methylation-based predictor of IC, trained on...

Mice missing the complex I subunit Ndufs4 of the electron transport chain are widely used as a leading animal model of Leigh syndrome, a pediatric neurodegenerative disorder that leads to premature death. More broadly, this animal model has enabled a better understanding of the pathophysiology of mitochondrial disease and mitochondrial dysfunction in sporadic disorders. Intriguingly, longevity interventions are very effective at treating symptoms of disease in this model. Herein, we introduce...

Intrinsic Capacity (IC) is a crucial measure of the comprehensive physiological and psychological capabilities of older adults, playing a key role in assessing healthy aging. This systematic review aims to explore the trajectories of IC in older adults, as well as the associated determinants and health outcomes. By searching through PubMed, Embase, Ovid, and Web of Science databases, we identified 13 studies that met our inclusion criteria. To ensure the rigor of the review, the Newcastle-Ottawa...

The excitation-inhibition ratio is a key functional property of cortical microcircuits which changes throughout an individual's lifespan. Adolescence is considered a critical period for maturation of excitation-inhibition ratio. This has primarily been observed in animal studies. However, there is limited human in vivo evidence for maturation of excitation-inhibition ratio at the individual level. Here, we developed an individualized in vivo marker of regional excitation-inhibition ratio in...

CONCLUSIONS: Our findings demonstrate that modifiable lifestyle patterns-specifically increased leisure-time physical activity, optimized sleep duration, and reduced sedentary behavior-are significantly associated with attenuated biological aging. These results suggest behavioral modifications may represent viable strategies for decelerating aging.

Myocardial infarction (MI) remains the leading cause of mortality and morbidity worldwide. It is caused by a thrombotic occlusion of coronary vessel/s that leads to cardiomyocyte death. As a response, inflammatory and fibrotic responses are initiated to replace the necrotic tissue and remodel the heart. However, in most cases, these responses are excessively activated, which accentuates the injury and causes adverse cardiac remodeling, often leading to heart failure. This is highly attributed to...

Age-associated neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis, are marked by progressive degeneration of the nervous system. Current diagnostic approaches, such as neuroimaging and cerebrospinal fluid biomarkers, are invasive, costly, and lack early diagnostic reliability. Recent studies highlight the potential of extracellular vesicles, particularly exosomes, derived from erythrocytes or red blood cells (RBCs), as...

Age-related increases in cerebral pulsatility are thought to stress cerebral microcirculation, with effects that may vary across different brain regions. The aging brain also undergoes neurofunctional changes to preserve and, in some cases, enhance cognitive abilities. This study investigated the association between cerebral pulsatility and neurofunctional changes in aging. Sixty healthy adults were divided into two groups of younger (aged 19-31 years) and older adults (aged 62-75 years)....

Hippocampal adult neural stem cells (NSCs) contribute to neurogenesis and astrogliogenesis throughout life. They play multifaceted roles in hippocampal function, including memory processing, stress regulation, and cognitive flexibility. Located in unique neurogenic niches like the subgranular zone of the hippocampal dentate gyrus, NSCs exhibit notable heterogeneity and can be classified into quiescent, activated, and intermediate transitioning states. This diversity, while instrumental to their...

The human kidney maintains homeostasis through a complex network of up to a million nephrons, its fundamental tissue units. Using innovative tissue processing and light sheet fluorescence microscopy, we mapped the 3D neurovascular connectivity of nephrons to understand how their structural organization enables coordinated functions like filtration, absorption, and blood pressure regulation. Our analysis revealed developmental changes in glomerular orientation, density, volume, and innervation...

Neural stem cells (NSCs) in the mammalian brain decline rapidly with age, leading to impairment of hippocampal memory function in later life. However, the relationship between epigenetic remodeling and transcriptional regulation that compromises hippocampal NSC activity during the early stage of chronological aging remains unclear. Here, we performed single-cell RNA sequencing (scRNA-seq) and single-cell ATAC sequencing (scATAC-seq) on NSCs and newly generated neurons across different stages....

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Caloric restriction and methionine restriction-driven enhanced lifespan and healthspan induces 'browning' of white adipose tissue, a metabolic response that increases heat production to defend core body temperature. However, how specific dietary amino acids control adipose thermogenesis is unknown. Here, we identified that weight loss induced by caloric restriction in humans reduces thiol-containing sulfur amino acid cysteine in white adipose tissue. Systemic cysteine depletion in mice causes...

Reactive thiols of proteinaceous cysteines are vital to cell biology by serving as sensor, effector and buffer of environmental redox fluctuations. Being the major source, as well as the prime target, of reactive oxygen species (ROS), mitochondria confront great challenges in preserving their thiol pool. Here we show that ROS modulator 1 (ROMO1), a small inner mitochondrial membrane protein, plays a role in protecting the mitochondrial cysteinome. ROMO1 is redox sensitive and reactive and...

Cellular senescence increases with age and contributes to age-related declines and pathologies. We identified circulating biomarkers of senescence and related them to clinical traits in humans to facilitate future noninvasive assessment of individual senescence burden, and efficacy testing of novel senotherapeutics. Using a nanoparticle-based proteomic workflow, we profiled the senescence-associated secretory phenotype (SASP) in THP-1 monocytes and examined these proteins in 1,060 plasma samples...

Aging alters morphology and locomotor function in diverse organisms, yet standardized model systems for studying these changes remain limited to a relatively few species. Here, we present a comprehensive analysis of age- and sex-dependent morphological variations in house crickets (Acheta domesticus), integrating refined husbandry protocols to enhance reproducibility and translational relevance. To ensure data consistency, we implemented a standardized husbandry framework incorporating...

Werner syndrome (WS) is a rare hereditary progeroid syndrome caused by mutations in the WRN gene. Patients frequently develop various age-associated diseases prematurely, often leading to early mortality (≤ 60 years of age). Depletion of nicotinamide adenine dinucleotide (NAD)^(+) has been reported in patients with WS, suggesting a key role in the pathogenesis of WS. NAD^(+) supplementation may improve the condition of WS and other accelerated aging diseases. Therefore, we conducted a...

Resilience is increasingly recognized as a central factor in how older adults adapt to life's inevitable changes, yet many clinicians remain unfamiliar with its practical applications in late life. Drawing on the true story of Cocota, a Brazilian matriarch who lived to be 100, this special article illustrates how resilience is neither a static trait nor limited to mere survival. Instead, it emerges over decades, shaped by early adversities and sustained through purposeful roles, strong social...

This research paper investigates the prevalence of functional limitations among employed adults in the United States and the association between these limitations and medical conditions. The authors administered a survey adapted from the Dutch Functional Abilities List to a nationally representative sample of US adults ages 22 and older, finding that nearly three-quarters of working adults report at least one functional limitation, with an average of nearly six functional limitations per working...