Ceramide Biomarkers Predictive of Cardiovascular Disease Risk Increase in Healthy Older Adults After Bed Rest

Abstract Acute bed rest places older adults at risk for health complications by disrupting homeostasis in many organ systems, including the cardiovascular system. Circulating ceramides are emerging biomarkers predictive of cardiovascular and metabolic health and have recently been shown to be sensitive indices of cardiovascular (CV) risk. Therefore, the purpose of this study was to characterize the time course of changes in circulating ceramides in healthy younger and older adults after 5 days of bed rest and to determine whether short-term bed rest alters CV-related circulating ceramides. We hypothesized that circulating ceramides predictive of poor cardiometabolic outcomes would increase following 5 days of bed rest. Thirty-five healthy younger and older men and women (young: n = 13, old: n = 22) underwent 5 days of controlled bed rest. Fasting blood samples collected daily during the course of bed rest were used to measure circulating ceramides, lipoproteins, adiponectin, and fibroblast growth factor 21 (FGF21) levels. The primary findings were that circulating ceramides decreased while ceramide ratios and the cardiac event risk test 1 score were increased primarily in older adults, and these findings were independent of changes in circulating lipoprotein levels. Additionally, we found that changes in circulating adiponectin, FGF21 and the 6-minute walk test (6MW) inversely correlated with CV-related circulating ceramides after bed rest. The results of this study highlight the sensitivity of circulating ceramides to detect potential CV dysfunction that may occur with acute physical disuse in aging.