Aging & Longevity

Skeletal muscle undergoes many alterations with aging. However, the impact of aging on muscle's ability to secrete myokines and its subsequent effects on the body remain largely unexplored. Here, we identify myokines that have the potential to ameliorate age-related muscle and bone decline. Notably, circulating levels of cardiotrophin-like cytokine factor 1 (CLCF1) decrease with age, while exercise significantly upregulates CLCF1 levels in both humans and rodents. Restoring CLCF1 levels in aged...

Maladaptive proximal tubular (PT) epithelial cells have been implicated in progression of chronic kidney disease (CKD), however the complexity of epithelial cell states within the fibrotic niche remains incompletely understood. Hence, we integrated snRNA and ATAC-seq with high-plex single-cell molecular imaging to generate a spatially-revolved multiomic atlas of human kidney disease. We demonstrate that in injured kidneys, a subset of HAVCR1^(+)VCAM1^(+) PT cells acquired an inflammatory...

Current approaches used to track stem cell clones through differentiation require genetic engineering^(1,2) or rely on sparse somatic DNA variants^(3,4), which limits their wide application. Here we discover that DNA methylation of a subset of CpG sites reflects cellular differentiation, whereas another subset undergoes stochastic epimutations and can serve as digital barcodes of clonal identity. We demonstrate that targeted single-cell profiling of DNA methylation⁵ at single-CpG resolution can...

CONCLUSIONS: This study identified the prevalence and specific patterns of multimorbidity among older hospital dental patients, providing essential insights for dental professionals to enhance service provision and manage complex multimorbidity cases.

Alzheimer's disease (AD) and traumatic brain injury (TBI) are currently untreatable neurodegenerative disorders afflicting millions of people worldwide. These conditions are pathologically related, and TBI is one of the greatest risk factors for AD. Although blood-brain barrier (BBB) disruption drives progression of both AD and TBI, strategies to preserve BBB integrity have been hindered by lack of actionable targets. Here, we identify 15-hydroxyprostaglandin dehydrogenase (15-PGDH), an enzyme...

The aging of mammalian epigenomes fundamentally alters cellular functions, and such changes are the focus of many healthspan and lifespan studies. However, studies of this process typically use mouse models living under standardized laboratory conditions and neglect the impact of variation in social, physical, microbial, and other aspects of the living environment on age-related changes. We examined differences in age-associated methylation changes between traditionally laboratory-reared mice...

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CONCLUSIONS: Higher social engagement in older adults is associated with reduced mortality risk possibly due to decreased biological aging and increased physical activity levels.

Loss of cognitive function is a significant challenge in aging, and developing models to understand and target cognitive decline is crucial for the development of Geroscience-based interventions. Aged mice offer a valuable model as they share features of cognitive decline with humans. Despite numerous studies, knowledge of longitudinal age-related cognitive changes and cognitive frailty in naturally aging mice is limited, particularly in cohorts exceeding 30 months of age, where cognitive...

T cell aging increases the risk of viral infection-related morbidity and mortality and reduces vaccine efficacy in the elderly. A major hallmark of T cell aging is the loss of quiescence and shift toward terminal differentiation during homeostasis. However, how aging impacts the differentiation program of virus-specific T cells during infection is unclear. Here, in a murine coronavirus (MHV) infection model with age-associated increased mortality, we demonstrate that aging impairs, instead of...

Metabolic disorders such as insulin resistance and hypertension are potential risk factors for aging and neurodegenerative diseases. These conditions are reversed in Chromogranin A (CgA) knockout (CgA-KO) mice. CgA is known to be associated with protein aggregates in the brains of neurodegenerative diseases including Alzheimer's disease (AD). Here, we investigated the role of CgA in Tau pathogenesis in AD and corticobasal degeneration (CBD). CgA ablation in Tauopathy mice (PS19) (CgA-KO/PS19)...

Chimeric antigen receptor (CAR) T cell therapy is one of the most promising cancer treatments. However, different hurdles are limiting its application and efficacy. In this context, how aging influences CAR-T cell outcomes is largely unknown. Here we show that CAR-T cells generated from aged female mice present a mitochondrial dysfunction derived from nicotinamide adenine dinucleotide (NAD) depletion that leads to poor stem-like properties and limited functionality in vivo. Moreover, human data...

Age-related hearing loss (ARHL) is among the most prevalent and complex disorders in older adults. However, the pathogenesis of ARHL remains poorly understood. Using a single-cell transcriptomic landscape of mouse cochlea at five time points (1, 2, 5, 12 and 15 months), we found that the levels of human antigen R (HuR)-a classical RNA-binding protein-increase with age. Here we show that HuR is specifically transported from the nucleus to the cytoplasm in hair cells in both aging mice and...

Whether and how endometrial aging affects fertility remains unclear. In our in-house clinical cohort at the Center for Reproductive Medicine of Peking University Third Hospital (n = 1,149), we observed adverse pregnancy outcomes in the middle-aged group after excluding aneuploid embryos, implying the negative impact of endometrial aging on fertility. To understand endometrial aging, we performed comprehensive transcriptomic profiling of the mid-secretory endometrium of young (<35 years) and...

The widespread use of single-cell RNA sequencing has generated numerous purportedly distinct and novel subsets of microglia. Here, we challenge this fragmented paradigm by proposing that microglia exist along a continuum rather than as discrete entities. We identify a methodological over-reliance on computational clustering algorithms as the fundamental issue, with arbitrary cluster numbers being interpreted as biological reality. Evidence suggests that the observed transcriptional diversity...

CONCLUSION: The study concludes that while FoF does not impair static balance, it significantly impacts movement initiation and execution in transitional tasks. Prolonged preparation time (S1) in the HIGH FoF group highlights the role of fear in delaying movement. These findings are important for designing interventions to reduce FoF and prevent falls in older adults.

CONCLUSION: This nomogram provides a robust tool for malnutrition risk stratification in nursing homes. Future studies should validate its generalizability across diverse populations and regions.

CONCLUSIONS: Poor stereopsis was associated with cognitive dysfunction and had increased odds for cognitive impairment. Our findings suggest a cross-sectional association between stereopsis and cognitive dysfunction in community-dwelling older adults.

CONCLUSION: Our findings align with previous studies involving participants of comparable age, indicating comparable results, apart from disease-related participation restrictions. However, the significant proportion of patients who did not want to participate (55.7%) and the analysis of the reasons for nonparticipation suggest that the actual number of geriatric patients who do not engage online is higher. While this does not necessarily imply a complete rejection of digital products by this...

CONCLUSIONS: Poor sleep quality was associated with reduced physical function, especially in with advancing ageand in women. Targeted interventions to enhance sleep in the elderly may contribute to maintaining physical function and improve the quality of life of such patients.