DNA methylation GrimAge strongly predicts lifespan and healthspan
Ake T. Lu, Austin Quach, James G. Wilson, Alex P. Reiner, Abraham Aviv, Kenneth Raj, Lifang Hou, Andrea Baccarelli, Yun Li, James D. Stewart, Eric A. Whitsel, Themistocles L. Assimes, Luigi Ferrucci, Steve Horvath
Abstract
.Using large scale validation data from thousands of individuals, we demonstrate that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death (Cox regression P=2.0E-75), time-to-coronary heart disease (Cox P=6.2E-24), time-to-cancer (P= 1.3E-12), its strong relationship with computed tomography data for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12). AgeAccelGrim is strongly associated with a host of age-related conditions including comorbidity count (P=3.45E-17). Similarly, age-adjusted DNAm PAI-1 levels are associated with lifespan (P=5.4E-28), comorbidity count (P= 7.3E-56) and type 2 diabetes (P=2.0E-26). These DNAm-based biomarkers show the expected relationship with lifestyle factors including healthy diet and educational attainment.Overall, these epigenetic biomarkers are expected to find many applications including human anti-aging studies.