Using Epigenetic Clocks to Characterize Biological Aging in Studies of Children and Childhood Exposures: a Systematic Review

Abstract

Biological age, measured via epigenetic clocks, offers a unique and useful tool for prevention scientists to explore the short- and long-term implications of age deviations for health, development, and behavior. The use of epigenetic clocks in pediatric research is rapidly increasing, and there is a need to review the landscape of this work to understand the utility of these clocks for prevention scientists. We summarize the current state of the literature on the use of specific epigenetic clocks in childhood. Using systematic review methods, we identified studies published through February 2023 that used one of three epigenetic clocks as a measure of biological aging. These epigenetic clocks could either be used as a predictor of health outcomes or as a health outcome of interest. The database search identified 982 records, 908 of which were included in a title and abstract review. After full-text screening, 68 studies were eligible for inclusion. While findings were somewhat mixed, a majority of included studies found significant associations between the epigenetic clock used and the health outcome of interest or between an exposure and the epigenetic clock used. From these results, we propose the use of epigenetic clocks as a tool to understand how exposures impact biologic aging pathways and development in early life, as well as to monitor the effectiveness of preventive interventions that aim to reduce exposure and associated adverse health outcomes.

Keywords: Biological adaptation; Biological clock; Epigenetic age; Hannum clock; Horvath clock; PedBE clock.

Fig. 1

PRISMA flow chart of identification and elimination of studies for review. The search was completed through February 2023 From: Moher D, Liberati A, Tetzlaff J, Altman DG, The PRISM Group (2009). Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISM Statement. PLoS Med 6(7): e1000097. doi: 10.1371/journal.pmed1000097