A Sex-Specific Minimal CpG-Based Model for Biological Aging Using ELOVL2 Methylation Analysis

Abstract

Significant deviations between chronological and biological age can signal the early risk of chronic diseases, driving the need for tools that accurately determine biological age. While DNA methylation-based clocks have demonstrated strong predictive power for biological aging determination, their clinical application is limited by several barriers including high costs, the need to analyze hundreds of methylation sites using sophisticated platforms and the lack of standardized measurement tools and protocols. In this study, we developed a multivariate linear model using the analysis of eight CpGs within the promoter region of the very long chain fatty acid elongase 2 gene (ELOVL2). The model generated predicts biological age with a mean absolute error (MAE) of 5.04, providing a simplified, cost-effective alternative to more complex methylation-based clocks. Additionally, we identified sex-specific biological clocks, achieving MAEs of 4.37 for males and 5.38 for females, highlighting sex-related molecular differences in the methylation of this gene during aging. Our minimal CpG-based clock offers a practical solution for estimating biological age, with potential applications in clinical practice for assessing age-related disease risks and providing personalized healthcare interventions.