Circulating ceramides are inversely associated with cardiorespiratory fitness in participants aged 54–96 years from the Baltimore Longitudinal Study of Aging

Abstract

SummaryCardiorespiratory fitness (VO 2 peak) declines with age and is an independent risk factor for morbidity and mortality in older adults. Identifying biomarkers of low fitness may provide insight for why some individuals experience an accelerated decline of aerobic capacity and may serve as clinically valuable prognostic indicators of cardiovascular health. We investigated the relationship between circulating ceramides and VO 2 peak in 443 men and women (mean age of 69) enrolled in the Baltimore Longitudinal Study of Aging (BLSA). Individual species of ceramide were quantified by HPLC–tandem mass spectrometry. VO 2 peak was measured by a graded treadmill test. We applied multiple regression models to test the associations between ceramide species and VO 2 peak, while adjusting for age, sex, blood pressure, serum LDL, HDL, triglycerides, and other covariates. We found that higher levels of circulating C18:0, C20:0, C24:1 ceramides and C20:0 dihydroceramides were strongly associated with lower aerobic capacity (P < 0.001, P < 0.001, P = 0.018, and P < 0.001, respectively). The associations held true for both sexes (with men having a stronger association than women, P value for sex interaction <0.05) and were unchanged after adjusting for confounders and multiple comparison correction. Interestingly, no significant association was found for C16:0, C22:0, C24:0, C26:0, and C22:1 ceramide species, C24:0 dihydroceramide, or total ceramides. Our analysis reveals that specific long‐chain ceramides strongly associate with low cardiovascular fitness in older adults and may be implicated in the pathogenesis of low fitness with aging. Longitudinal studies are needed to further validate these associations and investigate the relationship between ceramides and health outcomes.

A Lipidomics Approach to Assess the Association Between Plasma Sphingolipids and Verbal Memory Performance in Coronary Artery Disease Patients Undertaking Cardiac Rehabilitation: A C18:0 Signature for Cognitive Response to Exercise

“…Previously, better cardiopulmonary fitness was associated with lower plasma ceramide concentrations in healthy elderly subjects[82] and muscle ceramide concentrations were decreased following chronic aerobic exercise[83, 84]. The present study shows similar effect of exercise in CAD, a disease characterized by aberrant ceramide metabolism.…”

Beyond fitness tracking: The use of consumer-grade wearable data from normal volunteers in cardiovascular and lipidomics research

“…All significant sphingolipids were negatively associated with DailySteps. Of these, the specific sphingolipids most significantly ( p < 0.01; q < 0.1) associated with DailySteps included Cer(d18:1/18:0), Cer(d18:1/20:0), and Cer(d18:1/24:1(15Z)), ceramides previously reported to be negatively correlated with cardiorespiratory fitness as measured by peak oxygen consumption in volunteers [ 25 ]. We also identified associations among precursor dihydroceramides Cer(d18:0/20:0) and Cer(d18:0/24:1(15Z)), which have been linked to obesity [ 24 , 27 ].…”

Elevated plasma ceramide levels in post-menopausal women

“…The present study has several limitations. First, even though we excluded persons affected by obesity and diabetes, we did not collect information on metabolic factors that could potentially impact ceramide mobilization – such as adiposity, physical activity and levels of cholesterol and glucose in blood [18,49-51]. Second, our study was focused on a specific subset of ceramides that we had previously found to be altered in the hippocampus of aged male and female mice [19].…”