To assess the risk stratification ability of physiology-based biological aging and DNA methylation-based clocks for improving precision in detection of stroke risk.

Scaled up prevention strategies that allow wider coverage of individuals at stroke risk are limited by absence of personalized and sensitive biomarkers for early detection.

The present study included individuals who consented for blood draw in the Health and Retirement Venous blood substudy. Physiology-based assessment of biological aging based on 9 biomarkers was included (albumin, creatinine, glucose, C-reactive protein, lymophocyte percent, mean cell volume, red blood cell distribution width, alkaline phosphatase and white blood cell count). Biological aging based on DNA-methylation was assessed using clocks including Grim Age, Horvath and Phenotypic Age. The association was assessed using median splines and regression in whole sample and a subsample of matched stroke and stroke-free individuals. 

DNA methylation clocks showed a relatively slower rate of aging compared to physiology with significant differences. Among all individuals in the sample (N=3,410), one year increase in biological age based on physiology reflected changes in DNA methylation with coefficients ranging between 0.06, P<0.001 to 0.20, P<0.001. The estimates of biological aging observed were doubled among those with stroke, with coefficient= 0.12, P=0.03 for one year increase in physiology-based biological aging. The differences in the speed of biological aging between physiology and DNA methylation were further observed in median splines, with more pronounced variations among those younger than 50 or older than 75 years. 

Differences in biological aging based on physiology compared to DNA methylation were observed, with changes in physiology in asymptomatic patients at risk or on the trajectory of stroke progression being more influenced by aging processes than DNA methylation. Such variations seem to be more pronounced in healthy aging.