Aging & Longevity

Aging leads to neurodegenerative diseases, such as cognitive decline, which are induced by persistent chronic low-grade inflammation in the brain driven by microglial activation. However, whether and how brain-derived exosomes from aged mice (A-exo) induce a pro-inflammatory state and cellular senescence in microglia within the aging brain is poorly understood. Here, we report that brain-derived exosomes from aged mice (A-exo) cause cognitive decline in normal young mice, inducing microglial...

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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...

Alzheimer's disease, a progressive neurodegenerative disorder, is characterized by a decline in brain volume and neuronal loss, with early symptoms often presenting as short-term memory impairment. Automated classification of Alzheimer's disease remains a significant challenge due to inter-patient variability in brain morphology, aging effects, and overlapping anatomical features across different stages. While traditional machine learning techniques, such as Support Vector Machines (SVMs) and...

Global warming intensifies wildfires and exacerbates greenhouse gas and pollutant emissions¹. However, global projections remain incomplete, hindering effective policy interventions amid uncertain warming futures². Here, we developed an interpretable machine learning framework to project global burned areas and wildfire emissions. This framework accounts for the impacts of future climate change on fire activity and quantifies associated premature deaths and radiative forcing from fire-induced...

The mechanisms of aging are becoming increasingly well mapped; however, there remains ongoing debate about the ultimate and proximate causes of aging. The recent development of highly precise aging clocks led to a resurgence of arguments in support of a biological program of aging. However, the declining force of natural selection after the onset of reproduction means that cellular function could deteriorate without requiring a specific program. Here, we argue that aging clocks do not imply an...

Z-form DNA (Z-DNA)-binding protein 1 (ZBP1)-mediated RNA sensing plays a critical role in tumor immunogenicity. However, how to augment ZBP1 signaling-mediated immunogenic tumor cell death to boost targeted therapy is yet unknown. Here, we demonstrated that epigenetic modulation by 5-aza-2'-deoxycytidine (5AZA) facilitated antitumor effects of anti-HER2 therapy, which requires antitumor CD8^(+) T cell responses initiated by ZBP1-mediated tumor immunogenicity. Moreover, the combination of...

Poor sleep quality is associated with increased frailty in older adults, but the role of the gut microbiome in this relationship remains unclear. Here, gut metagenome and plasma metabolome were profiled in 1,225 individuals aged 62-96 years. Poor sleep quality was associated with reduced abundances of potential probiotics such as Faecalibacterium prausnitzii and elevated abundances of pathobionts. A gut microbiome sleep quality index (GMSI) was developed to quantify microbial balance related to...

CONCLUSIONS: Our study identifies a significant relationship between negative wealth shocks and biological aging in middle-aged and older adults. This suggests that socioeconomic factors, particularly sudden economic losses and fluctuations, should be considered in strategies for promoting healthy longevity and aging interventions. Additionally, there is a need for unemployment protection policies or measures to help stabilize medical and food consumption for households or individuals during...

Sleep entails profound changes in the brain and body, marked by altered states of consciousness and reduced somatic and autonomic motor activity. Regarding "how" sleep is regulated, whole-brain screening revealed large sleep-control networks spanning the forebrain, midbrain, and hindbrain. We unify diverse experimental evidence under a "motor theory," in which the sleep-control mechanism is integral to somatic and autonomic motor circuits. Regarding the "why" question, sleep deprivation impairs...

CONCLUSIONS: The BCW-based health promotion intervention effectively enhanced the well-being of migrant older adults by addressing their unique needs. The findings highlight the potential of tailored, multidimensional interventions to support this vulnerable population. Future research should explore long-term effects and cost effectiveness for broader implementation.

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Despite extensive research, significant uncertainty remains regarding the associations between various risk factors and ischemic stroke (IS). This study aimed to systematically identify and validate a broad range of potential modifiable risk factors for IS. Utilizing genetic and phenotypic data from the UK Biobank (UKB; N = 418,236), we conducted a phenome-wide association study (PheWAS) and Cox regression analysis to identify modifiable factors across sociodemographics, physical measures,...

GLP-1-based therapy is highly effective in combating aging-associated metabolic diseases. However, the metabolic effects of frequent withdrawal from this therapy in aged, obese mice have not been previously studied. In this study, aged obese UM-HET3 mice were assigned to three groups: Group 1 received no liraglutide treatment (Lira OFF); Group 2 underwent 3 cycles of treatment followed by withdrawal (Lira ON/OFF); and Group 3 remained on continuous treatment (Lira ON). As expected, mice in Group...

Considerable amounts of branched chain fatty acids (BCFAs) are present in the human diet from beef and dairy products. BCFAs can also be produced by the human gut microbiota and synthesized from branched chain amino acids. However, the physiological impact of a BCFA-rich diet on lipid metabolism and organismal health is unclear. In this study, by screening a collection of dietary bacteria, we find that the BCFA-rich Microbacterium diet causes the formation of supersized LDs and delays...