Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.

ABSTRACT: Epigenetic aging clocks have been widely used to validate rejuvenation effects during cellular reprogramming. However, these predictions are unverifiable because the true biological age of reprogrammed cells remains unknown. We present an analytical framework to consider rejuvenation predictions from the uncertainty perspective. Our analysis reveals that the DNA methylation profiles across reprogramming are poorly represented in the aging data used to train clock models, thus introducing high epistemic uncertainty in age estimations. Moreover, predictions of different published clocks are inconsistent, with some even suggesting zero or negative rejuvenation. While not questioning the possibility of age reversal, we show that the high clock uncertainty challenges the reliability of rejuvena

SUBMITTER: Kriukov D 

PROVIDER: S-EPMC11561706 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature