Priority Research Paper Volume 16, Issue 22 pp 13452—13504

Figure 1. Quantification of intrinsic and extrinsic aging. (A) Graphical depiction of how the predictive accuracy of an epigenetic clock derived from bulk-tissue can be decomposed in terms of an extrinsic and intrinsic aging process, as shown. The accuracy, measured by the R² value, of a clock reflecting the extrinsic process can be estimated from the given formula, if one can estimate the accuracies of the full unadjusted clock and the one fully adjusted for cell-type heterogeneity (CTH), the latter reflecting the intrinsic aging of the individual cell-types. (B) Barplots compare the R² values of the unadjusted clock, and clocks adjusted for 12 and 9 immune cell types, in each of 11 whole blood cohorts. Right panel displays the average and standard deviation of the two indicated ratios across the 11 cohorts. These ratios measure the fraction of the unadjusted clock’s accuracy that can be attributed to intrinsic aging. (C) As (B) but for brain DNAm datasets, where the adjusted clock was adjusted for 7 brain cell-types.