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Aging is a complex biological process characterized by the loss of metabolic homeostasis, epigenetic drift, and systemic functional decline. Although exercise is widely recognized as a potent non-pharmacological intervention for aging, the mechanisms by which it translates transient metabolic fluctuations into long-term systemic adaptations remain incompletely understood. During physical activity, skeletal muscle exhibits significantly enhanced glycolytic flux, leading to the accumulation of...

Alterations in the epigenetic transcriptome are crucial in the aging process and the occurrence of age-related diseases. This study aims to define global RNA methylation patterns in nursing home residents, an aged population with a high burden of age-related health deficits and sharing a common environment. The study was conducted on RNA samples extracted from blood samples of 56 older adults in a nursing home and of 36 young subjects living independently in their own homes. The RNA samples were...

CONCLUSIONS: Bed rest was associated with increases in frailty that were not fully reversed by four months. Exercise during bed rest could support earlier recovery. These findings highlight the harmful effects of bed rest and the potential role of exercise for hospitalised adults.

CONCLUSIONS: This study adds large-scale, population-based evidence on the associations between different PA intensities and NHHR. Regular moderate-to-vigorous PA is associated with more favorable lipid profiles and lower mortality risk. These findings highlight NHHR as a valuable biomarker linking physical activity to cardiometabolic health and longevity in middle-aged and older adults.

Immune-stromal crosstalk governs tissue fibrosis, which is marked by dysregulated extracellular matrix (ECM) production and aberrant vasculature. Here, we investigate how γδ T cell interactions with stromal cells shape fibrosis in the foreign body response in a murine biomaterial implant model. During the acute reaction, type-1 (γδIFNγ) and type-17 (γδ17) γδ T cell subsets accumulate at the implant site. While γδIFNγ cells decrease as fibrosis progresses, activated γδ17 cells persist as dominant...

Identifying robust, non-invasive biomarkers of biological age is key to preventive medicine. While gut aging clocks exist, the oral microbiome remains underexplored as a quantitative biomarker. Using oral microbiome data from two NHANES cohorts (N = 4,675), we identified 64 age-dependent bacterial genera and developed a machine learning model predicting chronological age, with generalizability in an independent external cohort (N = 1,293). We derived an Oral Microbiome Aging Acceleration (OMAA)...

BACKGROUND: The ageing population faces numerous physiological changes, among which immunosenescence plays a central role. Understanding the mechanisms underlying immunosenescence remains a priority. Within this framework, the contribution of comorbidities to immune dysfunction is still poorly characterized, despite growing evidence suggesting that it may represent a critical determinant in the evaluation of immunosenescence. The main objective of this report was to disentangle the respective...

Alzheimer's disease (AD) is a major cause of dementia and cognitive decline. Here, we assessed how episodic memory (EM) network dysfunction, a hallmark of AD, is related to the longitudinal progression of AD biomarkers, neurodegeneration and cognition using data from the DZNE DELCODE study. This data set includes over 1000 longitudinal functional magnetic resonance imaging measurements of EM network function. We related activation and deactivation of EM to individual disease progression scores...

Ageing leads to diurnal misalignment with a global reduction in physiological fitness, yet the mechanisms underlying such age-related diurnal reprogramming and its role in ageing remain poorly understood. Here we generate diurnal transcriptomes across eight peripheral tissues and reveal that disrupted redox oscillations are common diurnal alterations in organismal ageing. Restoring redox rhythms through the time-restricted application of antioxidants and pro-oxidants markedly improved glucose...

Metabolic processes shape ageing and longevity at multiple levels. Emerging evidence shows that many of these processes are orchestrated within and between cellular organelles. Organelles function not only as metabolic reactors but also as signalling hubs, and their coordination plays crucial roles in maintaining cellular homeostasis and promoting organismal fitness. Rather than acting in isolation, organelles engage in dynamic crosstalk through membrane contact sites, metabolite exchange and...

The brain is vulnerable to DNA damage and cardiometabolic risk. Yet, whether genetic variation in DNA repair interacts with cardiometabolic factors to explain cognitive variability remains unclear. Participants (n = 376,533) of white-British ancestry from the UK biobank with cognitive, neuroimaging, and whole-exome sequencing data were included. Six cognitive outcomes were assessed: fluid intelligence (FIQ), symbol-digit matching task (SDMT), visual matching (MATCH), trail making (TRAIL1 and...

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Senile osteoporosis is characterized by a progressive decline in bone formation. Our study identifies Zfp462/ZNF462 as a novel regulator of osteoblast differentiation, providing new mechanistic insights into the aging-related change in bone formation. Here, we demonstrate that ZNF462, MOZ, and RUNX2 physically interact with each other and promote osteoblastic bone formation by increasing RUNX2 activity and histone H3 acetylation. Importantly, we reveal that aging decreases ZNF462 expression in...

Aging-associated changes in myeloid cells are incompletely understood. One of the culprits of aging is the downregulation of the Tert gene coding for the catalytic subunit of telomerase. Studies of mouse models with Tert knockout (KO) in specific cells have revealed the importance of the telomere-independent noncanonical function of TERT in supporting mitochondrial metabolism and protection from cell senescence. To investigate the role of TERT in myeloid cells (MCs), we analyzed mice with Tert...

INTRODUCTION: Confluent evidence suggests that aging is associated with a reduction in the spectral slope of neural recordings. This phenomenon has been hypothesized to reflect an increase in the ratio of excitatory and inhibitory (E/I) balance. As neural E/I ratio is considered essential for cognitive functioning, this study investigated whether spectral slope (β) predicts cognitive performance in the older adults and could serve as a potential neural signature of cognitive aging. Nevertheless,...