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Dietary restriction (DR) improves insulin sensitivity, however, it has not been tested in long-term interventions and with diet type as variable. Therefore, we exposed mice to either a low-fat (LF) or high-fat-sucrose (HFS) diet, either fed ad libitum (AL) or in a DR regimen from weaning till 2 years of age. Using an oral glucose tolerance test with [6,6-²H(2)]-labelled glucose, we found that DR markedly reduced plasma insulin concentrations and strongly elevated hepatic and peripheral insulin...

Recently, we have identified rs1333046 as one of the candidate functional single nucleotide polymorphisms (fSNPs) on the atherosclerosis-associated CDKN2A/B locus. However, how rs1333046 influences the pathogenesis of and susceptibility to atherosclerosis is unknown. In this work, we demonstrate that rs1333046 is part of a cis-regulatory element (cis-RE) that regulates p16^(INK4a) and p16^(INK4a)-dependent cellular senescence in human endothelial cells (ECs). This is achieved by recruiting...

Social drivers of health (SDOH) impact health outcomes across the lifespan, with distinct effects on the health and well-being of older adults. SDOH contribute to outcomes of particular importance to older adults, including physical and cognitive functioning and aging in place, highlighting the critical importance of addressing SDOH as part of comprehensive, patient-centered geriatrics care. Yet, there is limited guidance on best practices for the integration of SDOH into healthcare,...

The mechanisms underlying skeletal muscle ageing, whilst poorly understood, are thought to involve dysregulated micro (mi)RNA expression. Using young and aged rat skeletal muscle tissue, we applied high-throughput RNA sequencing to comprehensively study alterations in miRNA expression occurring with age, as well as the impact of caloric restriction (CR) on these changes. Furthermore, the function of the proteins targeted by these age- and CR-associated miRNAs was ascertained. Numerous known and...

Epigenetic clocks are increasingly proposed as surrogate endpoints in aging trials, yet their short-term behavior in healthy older adults is not well characterized. We analyzed DNA methylation at baseline, year 1, and year 2 in 899 COSMOS-Blood participants (mean age 70.0; 50% women), deriving Horvath, Hannum, PhenoAge, and GrimAge clocks (original and principal component [PC] versions) and DunedinPACE. Epigenetic age acceleration was computed by regressing each clock on chronological age....