LC–MS/MS Profiling Reveals Age- and Sex-Dependent Trends in Blood Sphingolipids

Certain fats in your blood, called sphingolipids, can give extra insight into your risk of heart and metabolic diseases—sometimes more than standard tests. But before doctors can use this information routinely, they need to understand how these fat levels normally change with age and differ between men and women. To that end, Swiss researchers conducted a study aimed to characterize sphingolipid levels in clinically healthy individuals across the lifespan, with serum sphingolipids from 522 clinically healthy individuals aged 20 to 91 (48% females) quantified using targeted liquid chromatography-tandem mass spectrometry (LC-MS/MS). A paper based on their work was published in Communications Medicine.¹

How Do Excess Dietary Fat and Sphingolipids Affect Metabolism, Disease Risk, and Aging?

When you take in more calories than your body uses—or have ongoing inflammation—your usual fat storage fills up. The extra fat then gets turned into other types of fats, including sphingolipids. These can build up in organs like the muscles and liver, especially in a form called ceramides. Too much of these fats interferes with how your cells handle sugar, encourages more fat buildup, and makes your cells less efficient at producing energy. Early on, this can lead to problems like insulin resistance and fatty liver. If it continues, the excess fat becomes toxic and can contribute to serious conditions like heart disease, advanced liver disease, and type 2 diabetes.^2,3

Levels of these fats—especially ceramides—tend to be higher in older people, which suggests they may be involved in the aging process. In studies with mice, blocking the body’s production of these fats lowered their levels in muscle, helped build more muscle, and improved strength, suggesting it could help prevent age-related muscle loss.^4,5

How Do Sphingolipid Levels Change with Age and Sex?

Associations between sphingolipids and age were assessed for this study using multiple linear regressions adjusted for sex, cardiorespiratory fitness, and other confounding variables. Descriptive age- and sex-specific sphingolipid quantile curves were modelled using generalized additive models for location, scale, and shape.¹

The researchers found that 14 of the 21 detected sphingolipids were significantly and positively associated with age in both sexes. All four of the sphingolipids used in heart risk tests increased as people got older, but the ratios between them didn’t really change with age. Women generally had higher levels than men for several of these fats. The study also provides typical ranges for these levels by age and sex (from 20 to 90 years old). Links between fitness levels and these fats were mixed, depending on the specific type.¹

“Association analyses,” wrote the authors of the paper,¹ “revealed that age significantly influenced the circulating levels of 14 sphingolipid species. Descriptive, age-specific quantile curves complemented this finding, showing a global accumulation of circulating sphingolipids in both sexes. These results underscore the importance of considering age when assessing cardiometabolic risk with sphingolipid-based scores.”

“Notably,” the authors continue,¹ “ratios of deleterious to neutral sphingolipids were independent of age. This may suggest that while overall sphingolipid accumulation is linked to aging, these ratios could more closely reflect current cardiometabolic status. Nonetheless, this observation must be interpreted cautiously, as causal inferences cannot be drawn from cross-sectional data."

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References

1. Carrard, J.; Gallart-Ayala, H.; Infanger, D. et al. Lifespan Trajectories of Serum Sphingolipids in a Clinically Healthy Swiss Population, Towards Precision Medicine in Cardiometabolic Health Assessment. Commun Med (Lond). 2026.DOI: 10.1038/s43856-026-01565-y
2. Nicholson, R. J.; Norris, M. K.; Poss, A. M. et al. The Lard Works in Mysterious Ways: Ceramides in Nutrition-Linked Chronic Disease. Annu. Rev. Nutr. 2022, 42 (1), 115-144. DOI: 10.1146/annurev-nutr-062220-112920
3. Hannun, Y. A.; Obeid, L. M. Sphingolipids and their Metabolism in Physiology and Disease. Nat Rev Mol Cell Biol. 2018, 19 (3), 175-191. DOI: 10.1038/nrm.2017.107
4. Slade, E.; Irvin, M. R.; Xie, K. et al. Age and Sex Are Associated with the Plasma Lipidome: Findings from the GOLDN Study. Lipids Health Dis. 2021, 20 (1), 30. DOI: DOI: 10.1186/s12944-021-01456-2
5. Laurila, P-P.; Wohlwend, M.; Imamura de Lima, T. et al. Sphingolipids Accumulate in Aged Muscle, and Their Reduction Counteracts Sarcopenia. Nat Aging 2022, 2 (12), 1159-1175. DOI: 10.1038/s43587-022-00309-