Aging & Longevity

Cortical function, including sensory processing, is surprisingly resilient to neuron loss during aging and neurodegeneration. In this Article, we used the mouse auditory cortex to investigate how homeostatic mechanisms protect the representational map of sounds after neuron loss. We combined two-photon calcium imaging with targeted microablation of 30-40 sound-responsive neurons in layer 2/3. Microablation led to a temporary disturbance of the representational map, but it recovered in the...

CONCLUSIONS: By merging national data and distinguishing emotional from social loneliness, this study offers insights into their differential impacts on healthcare utilization among older adults in Taiwan. It emphasizes the importance of addressing loneliness to improve physical and mental well-being and optimize the effective utilization of healthcare resources.

Low circulating taurine concentrations have been proposed as a driver of the aging process. We found that circulating taurine concentrations increased or remained unchanged with age in three geographically distinct human cohorts as well as in nonhuman primates and mice when measured longitudinally (repeatedly in the same population) or cross-sectionally (sampling distinct populations at various ages). Moreover, considerable variability was observed in associations between taurine and age-related...

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CONCLUSIONS: The study showed an association between quantitatively assessed visual and physical functions in community-dwelling older adults living in Japan. Thus, the findings indicate that maintaining and enhancing grip strength and visual function in older adults may be an important factor in leading a healthy and fulfilling life.

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Gene editing (GE) using homology-directed repair (HDR) in hematopoietic stem and progenitor cells (HSPCs) offers promise for long-range gene correction of inherited genetic disorders. However, cellular responses induced by CRISPR-Cas9/AAV6 engineering impair the long-term repopulating potential of HDR-edited HSPCs, adversely impacting the safety and efficacy of clinical translation. Our study uncovers a durable senescence-like response in genetically engineered HSPCs triggered by p53 and...

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....