GDF-15 as a Biomarker of Aging
Researchers here provide evidence for circulating GDF-15 to increase with age and correlate with aging clock assessments of biological age. In the long term, more biomarkers can only help to improve our understanding of aging and the ability to measure aging sufficiently well to guide research and development to the most effective therapies. In the short term, the proliferation of interesting biomarkers is outpacing the exploration of their value. Considerable work and expense lies between where we stand now and a good understanding of how and why aging clocks work, and perhaps more importantly, how specific underlying processes of aging map to specific components of the clock measurements.
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.