Do circulating sphingolipid species correlate with age? A study in a normoglycemic biracial population

Sphingolipids (SPLs) are essential membrane lipids with significant bioactive roles involved in various cellular processes, and their alterations have been found to be linked to many diseases, including age-related diseases. However, comprehensive studies on the association of plasma sphingolipids with aging in large, diverse cohorts remain limited. The objective of this study was to investigate the relationship between plasma sphingolipid levels and aging in a cohort of 240 normoglycemic, biracial individuals (Black and White), aged 19-65 years. Using a targeted lipidomics approach, we measured 76 sphingolipid species using liquid chromatography-tandem mass spectrometry (LC-MS/MS) in picomole/mL and determined changes in their levels with age and their correlations with aging. We found significant age-related changes in several sphingolipid species, including ceramide C18:1 and several very long-chain sphingomyelins (VLC SMs), such as C28:1 and C30:1, increases with age, showing a positive correlation. On the other hand, glycosphingolipids (monohexosylceramide, MHC; lactosylceramide, LacCer) and sphingosine (So) showed strong negative correlations with aging. A significant correlation was also observed between the ratios of saturate/monosaturated sphingolipid species with aging. In conclusion, our findings provide novel insights into the dynamic changes of circulating sphingolipids with aging. Specific sphingolipid species, such as Ceramide C18:1 and SM, accumulate with age, while others, including MHC, LacCer, and So decrease. These results suggest that the plasma SPL profile may provide valuable information about healthy aging and age-associated disease conditions.