GDF-15 as a Proxy for Epigenetic Aging: Associations with Biological Age Markers, and Physical Function

Growth differentiation factor 15 (GDF-15) has emerged as a significant biomarker of aging, linked to various physiological and pathological processes. This study investigates circulating GDF-15 levels in a cohort of healthy individuals from the Balearic Islands, exploring its associations with biological age markers, including multiple DNA methylation (DNAm) clocks, physical performance, and other age-related biomarkers. Seventy-two participants were assessed for general health, body composition, and physical function, with GDF-15 levels quantified using ELISA. Our results indicate that GDF-15 levels significantly increase with age, particularly in individuals over 60. Strong positive correlations were observed between GDF-15 levels and DNAm GrimAge, DNAm PhenoAge, Hannum, and Zhang clocks, suggesting that GDF-15 could serve as a proxy for epigenetic aging. Additionally, GDF-15 levels were linked to markers of impaired glycemic control, systemic inflammation, and physical decline, including decreased lung function and grip strength, especially in men. These findings highlight the use of GDF-15 as a biomarker for aging and age-related functional decline. Given that GDF-15 is easier to measure than DNA methylation, it has the potential to be more readily implemented in clinical settings for broader health assessment and management.