Abstract: The disclosure provides seven DNAm-based estimators of plasma protein levels including those of plasminogen activation inhibitor 1 (PAI-1) and growth differentiation factor 15 (GDF15). The predictor of lifespan, DNAm GrimAge (in units of years), is a composite biomarker based on the seven DNAm surrogate markers and a DNAm-based estimator of smoking pack-years. These novel DNAm based biomarkers show the expected relationship with lifestyle factors (including healthy diet or educational attainment) and clinical biomarkers. Overall, these DNAm based biomarkers are expected to find many useful applications including human anti-aging studies.

Abstract: The invention disclosed herein is a DNA methylation-based estimator of human telomere length (“DNAmTL”) that is based on 140 CpGs, and is applicable across the entire age spectrum. DNAmTL is even more strongly associated with chronological age than is measured TL (r˜?0.75 for DNAmTL versus r˜?0.35 for TL) and outperforms the latter in predicting i) time-to-death (P=4.1E-15), ii) time-to-coronary heart disease (p=6.6E-5), and iii) time-to-congestive heart failure (p=3.5E-6); all of which were corroborated with large sets of blood methylation data (N=6,850). DNAmTL is also associated with non-pathological conditions including physical functioning (P=7.6E-3), age-at-menopause (P=0.039), dietary variables (omega 3, fish, vegetable), educational attainment (P=4.3E-6) and income (P=3.1E-5). DNAmTL is an attractive molecular biomarker of aging due to its superior performance to measured TL, its intuitive interpretation of telomere length, its ease of use in vivo and in vitro, and its robustness.