Lifespan trajectories of serum sphingolipids in a clinically healthy Swiss population, towards precision medicine in cardiometabolic health assessment

Measurements of blood sphingolipids have previously been shown to predict cardiometabolic risk beyond traditional biomarkers. However, before these scores can be implemented in clinical practice, it is essential to establish lifespan trajectories and age- and sex-specific values for sphingolipid levels. This cross-sectional study aimed to characterise sphingolipid levels in clinically healthy individuals across the lifespan. Serum sphingolipids from 522 clinically healthy individuals aged 20 to 91 of the COmPLETE-Health study (48% females) were quantified using targeted liquid chromatography-tandem mass spectrometry. Associations between sphingolipids and age were assessed using multiple linear regressions adjusted for sex, cardiorespiratory fitness, and other confounding variables. Descriptive age- and sex-specific sphingolipid quantile curves were modelled using generalised additive models for location, scale, and shape. Fourteen of the 21 detected sphingolipids were significantly and positively associated with age in both sexes. Notably, all four sphingolipids included in the Cardiovascular Event Risk Tests (Cer16:0, Cer18:0, Cer24:0, and Cer24:1) increased with age, whereas their respective ratios were not significantly associated with age. Females exhibited significantly higher levels than males for four sphingomyelins, two ceramides, HexCer18:0, and the Cer16:0/Cer24:0 ratio. Age- and sex-specific values across the lifespan (20 to 90 years) are provided as percentiles. Associations between cardiorespiratory fitness and sphingolipid levels varied by species. Serum sphingolipid levels depended on age, underscoring the need for age-specific interpretation when assessing cardiometabolic risk using sphingolipid-based scores. Conversely, sphingolipid ratios remained unaffected by age. Carrard, Gallart-Ayala et al. quantify serum sphingolipids across adulthood using targeted lipidomics in a clinically healthy population. They show that several sphingolipids, including ceramides used in cardiometabolic risk scores, increase with age, highlighting the need for age-specific interpretation. Certain blood lipids, called sphingolipids, can help predict the risk of heart and metabolic diseases. To use these markers properly, it is important to understand how their levels normally change with age and between women and men. In this study, we measured sphingolipids in blood samples from more than 500 healthy adults aged 20 to 91 years. We analysed how sphingolipid levels varied across the lifespan while accounting for sex, fitness, and other health factors. We found that many sphingolipids increase steadily with age, including those used in existing cardiovascular risk scores, whereas their ratios remain stable. Women and men also exhibited distinct patterns across several sphingolipids. These results provide age- and sex-specific values that can improve the interpretation of sphingolipid markers in future cardiometabolic research.