EPIGENETIC CLOCKS OF COMPUTED TOMOGRAPHY MEASURES OF FATTY ORGANS

DNA methylation (DNAm) based biomarkers collectively known as “epigenetic clock” yielding accurate measure of age in any tissue across the entire life course have associated with a large host of age-related conditions. To study their implications in metabolic syndromes, we analyzed computed tomography (CT) derived measures of adiposity with 1) three widely-used clocks: Horvath, Hannum, and Levine (PhenoAge), and a newly developed clock DNAmGrimAge, and 2) seven DNAm based plasma proteins, the components comprising the DNAmGrimAge. Age-adjusted DNAmGrimAge and several age-adjusted DNAm plasma proteins including plasminogen activation inhibitor 1 (PAI-1) stand our followed by adrenomedullin and leptin. Fatty liver (r ≤ 0.41, P ≤ 2.9E-37) and excess visceral adipose tissue fat (r ≤0.42, P ≤ 1.5E-41) are the most significant CT-based measures of DNAmPAI-1 and DNAmGrimAge. Furthermore, age-adjusted DNAmGrimAge and age-adjusted DNAmPAI-1 continued showing the most significant relationship with lifestyle factors including healthy diet and educational attainment in expected directions.