Aging & Longevity

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...

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...

No abstract

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,...

Stem cells proliferate after injury to repair damaged tissue, and chronic injury can promote cancer. However, the injury-activated signals and regulatory mechanisms, and their relationship to cancer, are poorly understood. Here, we identified insulin-like growth factor 2 (Igf2) as an injury-activated mitogen for lung neuroendocrine stem cells, which are facultative airway progenitors and a cell of origin of small-cell lung cancer in mice. Igf2 was constitutively produced by the stem cells but...

Cardiovascular risk (CVR) factors exert effects that extend beyond the vascular system, influencing brain structure, neural function, and cognitive performance. The mechanisms by which CVR factors exert these effects remain unclear. Here, we specifically investigate the impact of CVR factors on brain aging, testing whether quantitative measures of the heart and major arteries mediate the CVR-brain-age relationship. Using longitudinal UK Biobank data, we infer individual brain age estimates based...

The benign-to-malignant transition is a defining step in cancer progression. To investigate when and how malignancy initiation occurs and tissue reorganization proceeds, we combine single-cell and spatial transcriptomic profiling in mouse models of pancreatic ductal adenocarcinoma (PDAC) that capture spontaneous p53 loss. Among Kras-mutant cells, we find that oncogenic and tumor-suppressive programs, including those controlled by p53, CDKN2A, and SMAD4, are co-activated in a discrete...

CONCLUSIONS: In diabetic patients, elevated baseline ePWV is an independent predictor of a persistently low cognitive trajectory over a 9-year period. This association appears to be partially mediated by accelerated biological aging, suggesting that vascular stiffness may act as a systemic driver of cognitive compromise.

Memory complaints indicate the self-reported experience of memory failures or difficulties in daily life. While different measures of functional and psychological health seem to be associated with memory complaints in later life, the concurrent impact of perceived physical health, memory self-efficacy, and objectively measured motor and sleep parameters remains under-examined. This study addressed this gap by recruiting 118 community dwellers (M(age) = 81.7 years, SD = 8.1 years) from the...

No abstract

Ocular rosacea (OR) is a chronic inflammatory disease of the ocular surface frequently associated with meibomian gland dysfunction (MGD), with limited therapeutic options and an underexplored pathophysiology. Here, we uncover the pivotal role of mineralocorticoid receptor (MR) pathway overactivation in driving MGD and OR. Analysis of eyelid tissues from OR patients revealed increased MR expression and altered local corticosteroid metabolism, associated with inflammation, fibrosis, and impaired...