Developing an understanding of the biochemistry of aging in both sexes is critical for managing disease throughout the lifespan. Lipidomic associations with age and sex have been reported, but prior studies are limited by measurements in serum rather than plasma or by participants taking lipid-lowering medications.

Our study included lipidomic data from 980 participants aged 18–87 years old from the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN). Participants were off lipid-lowering medications for at least 4 weeks, and signal intensities of 413 known lipid species were measured in plasma. We examined linear age and sex associations with signal intensity of (a) 413 lipid species; (b) 6 lipid classes (glycerolipids, glycerophospholipids, sphingolipids, sterol lipids, fatty acids, and acylcarnitines); and (c) 15 lipid subclasses; as well as with the particle sizes of three lipoproteins.

Significant age associations were identified in 4 classes, 11 subclasses, 147 species, and particle size of one lipoprotein while significant sex differences were identified in 5 classes, 12 subclasses, 248 species, and particle sizes of two lipoproteins. For many lipid species (n = 97), age-related associations were significantly different between males and females. Age*sex interaction effects were most prevalent among phosphatidylcholines, sphingomyelins, and triglycerides.

We identified several lipid species, subclasses, and classes that differ by age and sex; these lipid phenotypes may serve as useful biomarkers for lipid changes and associated cardiovascular risk with aging in the future. Future studies of age-related changes throughout the adult lifespan of both sexes are warranted.

Trial registration
ClinicalTrials.gov NCT00083369; May 21, 2004.

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Published in Lipids in Health and Disease, v. 20, article no. 30.

© The Author(s) 2021

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Funding Information

GOLDN biospecimens and baseline phenotype data were collected with funding from National Heart, Lung, and Blood Institute (NHLBI) grant U01HL072524. This work was also supported in part by grants from the National Center for Advancing Translational Sciences (UL1TR001998), the National Institute of Diabetes and Digestive and Kidney Diseases (1R01DK113625), the National Institute on Aging (1R56AG057589), the NHLBI (R01HL091357), the National Institute of General Medical Sciences (1P20GM130456), and the American Heart Association (15SDG25760020).

Related Content

The data that support the findings of this study are available from the corresponding author upon reasonable request.

12944_2021_1456_MOESM1_ESM.docx (76 kB)
Additional file 1. Continuation of Table 4. Associations between lipid signal intensity with age, sex, and their interaction (includes all lipid species).

12944_2021_1456_MOESM2_ESM.docx (135 kB)
Additional file 2. Correlation between total class intensities.

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Additional file 3. Diagnostic plots for regression models of lipid classes and subclasses.