Plasma Sphingolipids are Associated with Gait Parameters in the Mayo Clinic Study of Aging

Background Disrupted gait has been associated with an increased risk of frailty, disability, and death, but the causal molecular pathways are not well understood. Sphingolipids, including ceramides, are associated with multiple age-related diseases. Ceramides promote atrophy, necrosis, and proteolysis in cellular and animal models, and ceramide C16:0 levels are negatively correlated with muscle mass in men. However, there is a paucity of evidence examining sphingolipids and physical function. Methods We examined the cross-sectional association between plasma ceramides, sphingosine-1-phosphate (S1P), and ceramide/S1P ratios and gait, a robust measure of physical function, in 340 clinically normal participants aged 70 years and older enrolled in the Mayo Clinic Study of Aging. GAITRite® instrumentation was used to measure gait speed, cadence, step width, double support time, and intra-individual stride time variability. Based on previous studies, we hypothesized that higher plasma levels of ceramide C16:0 would be associated with worse gait. Results Multivariable adjusted linear regression models revealed that higher levels of ceramide C16:0 were associated with slower gait speed, decreased cadence, and increased double support time. Conclusions These results suggest an association between plasma ceramide C16:0 and physical function. Longitudinal studies are needed to determine whether elevated ceramide C16:0 can be utilized as a prognostic marker for functional decline.