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A long-standing question in biology and medicine concerns how astrocytes influence neurons. Here, progress concerning how astrocytes affect neurons and neural circuits is summarized by focusing on data and concepts from studies of the striatum, which has emerged as a model nucleus. Mechanisms broadly applicable across brain regions and disorders are emphasized, and knowledge gaps are described. Experiments spanning multiple scales of biology show that astrocytes regulate neural circuits by...

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Aggregation of α-synuclein (α-syn) represents a pathogenic hallmark of Parkinson's disease (PD). Using exogenous molecular chaperone systems has the potential to stabilize native conformations and inhibit the aberrant aggregation of α-syn, yet inefficient blood-brain barrier (BBB) penetration and insufficient accumulation at PD sites limit their application. Herein, we developed chemotactic chaperone nanomotors (CNMs) that exploit the unique pathological microenvironment of PD lesions,...

The transcription factor CCAAT/enhancer binding protein alpha (C/EBPα) regulates cell differentiation, proliferation, and function in various tissues, including the liver, adipose tissue, skin, lung, and hematopoietic system. Studies in rats, mice, humans, and chickens have shown that CEBPA mRNA undergoes alternative translation initiation, producing three C/EBPα isoforms. Two of these isoforms act as full-length transcription factors with N-terminal transactivation domains and a C-terminal...

Microglia, the brain's resident immune cells, are crucial for maintaining healthy brain homeostasis. However, as the brain ages, microglia can shift from a neuroprotective to a neurotoxic phenotype, contributing to chronic inflammation and promoting neurodegenerative processes. Despite the importance of understanding microglial aging, there are currently few human in vitro models to study these processes. To address this gap, we have developed a model in which human microglia undergo accelerated...

Cellular senescence is an irreversible form of cell-cycle arrest caused by excessive stress or damage. While various biomarkers of cellular senescence have been proposed, there are currently no universal, stand-alone indicators of this condition. The field largely relies on the combined detection of multiple biomarkers to differentiate senescent cells from non-senescent cells. Here we introduce a new approach: unbiased cell culture selections to identify senescent cell-specific folded DNA...

Rapamycin (RAPA) and related mTOR-inhibitors have been shown to enhance healthy aging in animal models (2-10) and to be generally safe and tolerable in older people (11-13). However, studies to assess their effects on specific age-related pathologies in humans are limited. Since improvements in cardiovascular function with RAPA treatment have been reported in preclinical studies (5, 9, 10, 14-17), we posited that RAPA could be similarly efficacious in humans. Towards this end, we performed a...

Periodontal disease (PD) is a chronic inflammatory condition linked to systemic health issues, yet its relationship with intrinsic capacity (IC)-a key determinant of healthy aging-remained underexplored. The present study investigated the associations between moderate/severe PD and IC domains in older adults in a cross-sectional analysis from the National Health and Nutrition Examination Survey (NHANES) 2009-2014. From the 30,468 NHANES subjects, we included participants aged ≥ 60 years with...

The interaction between sleep, circadian rhythms and cardiovascular resilience is a crucial yet underexplored research area with important public health implications. Disruptions in sleep and circadian rhythms exacerbate hypertension, diabetes mellitus and obesity, conditions that are increasingly prevalent globally and increase the risk of cardiovascular disease. A National Heart, Lung, and Blood Institute workshop examined these connections, as well as the emerging concept of cardiovascular...

Political directives have undermined agency's independence and record of supporting the best basic research