Abstract Body: Background: Individuals of the same chronological age often show considerable variation in health due to differences in biological aging, the process of accumulating molecular and cellular damage. Because lipidomics has shown strong associations with cardiometabolic disorders, we hypothesize that a lipidomic aging clock can more accurately reflect metabolic health and serve as a more powerful predictor of cardiometabolic disorders. We aim to assess the lipidomic aging clock and its associations with cardiometabolic disorders in American Indians.
Methods: We quantified 1,542 lipid species from 1,800 American Indian adults (mean age 40.0, 62.3% women) in the Strong Heart Family Study (2001-2003) using untargeted LC-MS lipidomics. A lipidomic aging clock was constructed by regressing chronological age on 1,542 standardized lipid species using elastic-net, adjusting for sex and BMI. We defined lipidomic age acceleration (mAgeΔ) as the residual of lipidomic age regressed on chronological age. Finally, we used logistic mixed-effects models (adjusted for age, sex and LDL-C) to evaluate associations of mAgeΔ quintiles with obesity, hypertension, and type 2 diabetes (T2D).
Results: Among the 1,800 participants, the prevalence of cardiometabolic disorders was high: obesity (54%), hypertension (28%), and T2D (17%). The constructed lipidomic aging clock was strongly correlated with chronological age (Pearson r = 0.78). Compared to those in the bottom quintile (Q1) of lipidomic age acceleration, participants in the top quintile group (Q5) showed significantly higher odds for all outcomes: obesity (OR = 1.48, 95% CI: 1.09-2.02), hypertension (OR = 1.52, 95% CI: 1.04-2.23), and T2D (OR = 1.81, 95% CI: 1.26-2.62).
Conclusion: Accelerated lipidomic aging is significantly associated with higher odds of obesity, hypertension, and diabetes in American Indians. These findings underscore the potential of the lipidomic aging clock as a powerful and precise biomarker of current cardiometabolic health.