Epistemic uncertainty challenges aging clock reliability in predicting rejuvenation effects.

Autor: Kriukov D; Skolkovo Institute of Science and Technology, Moscow, Russia.; Artificial Intelligence Research Institute, Moscow, Russia., Kuzmina E; Skolkovo Institute of Science and Technology, Moscow, Russia.; Artificial Intelligence Research Institute, Moscow, Russia., Efimov E; Skolkovo Institute of Science and Technology, Moscow, Russia., Dylov DV; Skolkovo Institute of Science and Technology, Moscow, Russia.; Artificial Intelligence Research Institute, Moscow, Russia., Khrameeva EE; Skolkovo Institute of Science and Technology, Moscow, Russia.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2024 Jul 28, pp. e14283. Date of Electronic Publication: 2024 Jul 28.
DOI: 10.1111/acel.14283
Abstrakt: 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 rejuvenation effects observed during in vitro reprogramming before pluripotency and throughout embryogenesis. Conversely, our method reveals a significant age increase after in vivo reprogramming. We recommend including uncertainty estimation in future aging clock models to avoid the risk of misinterpreting the results of biological age prediction.
(© 2024 The Author(s). Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
Externí odkaz: