Aging & Longevity

T-cell metabolism is a key regulator of immune function. Metabolic dysfunction in T cells from young mice results in an aged phenotype, accelerating immunosenescence. Physical activity (PA) maintains T-cell function and delays immunosenescence in older adults, but the underlying mechanisms are poorly understood. We investigated the effects of PA on the metabolic and functional profiles at a single-cell resolution of resting and stimulated T cells from young adults (N = 9, 23 ± 3 years) and...

BACKGROUND: We examined the efficacy of physical exercise with nutritional lectures in preventing cognitive decline among older adults.

Alzheimer's disease (AD) is a neurodegenerative condition associated with aging. As the population ages, the incidence of AD has risen annually, making it the fourth leading cause of death, following cardiovascular disease, cancer, and stroke. The main pathological features of AD are now thought to include the accumulation of extracellular amyloid-β (Aβ) plaques, the formation of intracellular neurofibrillary tangles, and a reduction in synaptic connections in the cerebral cortex and...

CONCLUSION: The comprehensive clinical use of multiple laboratory biomarkers can contribute both to the early identification of trajectories of cognitive and functional decline in older adults, and to the identification of mechanisms underlying the effect of multidisciplinary interventions on age-related pathological processes.

The salivary gland (SG) is vital for oral function and overall health through secretion of saliva. However salivary dysfunction due to aging, medications, autoimmune disorders, and cancer treatments poses significant challenges. We established the first diverse and clinically annotated salivary regenerative biobank at Mayo Clinic to study salivary gland stem/progenitor cells (SGSPCs). Optimization of cell isolation and progenitor assays revealed SGSPCs enriched within the CD24/EpCAM/CD49f+ and...

Lymph nodes (LN) are the key organs in charge of long-term maintenance of naïve lymphocytes and their initial, primary activation upon infection. Accumulating evidence indicates that LN stromal cells undergo degenerative changes with aging that critically impair LN function, including the generation of protective primary immune responses. The nature of these defects remains incompletely understood. We here demonstrate that age-related LN stromal changes manifest themselves in mitochondrial...

CONCLUSIONS: ICs generally accepted the use of CR, but they also reported some concerns about using CR for implement. In order to support the safe, equitable, and people-oriented implementation of CR in the long-term care system, we propose consider the ICs' attitudes to optimize CR, offer more technical support to IC, and find a way to balance the conflict of use right between IC and their care recipients in the use of CR.

The sense of smell is essential for human perception. Olfactory function declines with increasing age, affecting a substantial portion of the elderly population, and this decline is more pronounced in men. This reduction can be attributed to anatomical and degenerative changes in the brain and olfactory receptors. There is robust clinical evidence indicating an association between olfactory perception decline/deficit (OPD) and major neurodegenerative diseases, with severe deficits observed in...

CONCLUSIONS: These findings identify self-perceptions of aging as a strong predictor of physical recovery and disability following a fall, independent of other important factors such as age, gender, and pre-fall physical function. These novel observations advance our understanding of the psychological factors impacting physical recovery from a fall. Future work should explore if targeting such perceptions can directly improve physical recovery and outcomes following a fall.

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)...