“Epigenetic clocks”: Theory and applications in human biology

Abstract

All humans age, but how we age—and how fast—differs considerably from person to person. This deviation between apparent age and chronological age is often referred to as “biological age” (BA) and until recently robust tools for studying BA have been scarce. “Epigenetic clocks” are starting to change this. Epigenetic clocks use predictable changes in the epigenome, usually DNA methylation, to estimate chronological age with unprecedented accuracy. More importantly, deviations between epigenetic age and chronological age predict a broad range of health outcomes and mortality risks better than chronological age alone. Thus, epigenetic clocks appear to capture fundamental molecular processes tied to BA and can serve as powerful tools for studying health, development, and aging across the lifespan. In this article, I review epigenetic clocks, especially as they relate to key theoretical and applied issues in human biology. I first provide an overview of how epigenetic clocks are constructed and what we know about them. I then discuss emerging applications of particular relevance to human biologists—those related to reproduction, life‐history, stress, and the environment. I conclude with an overview of the methods necessary for implementing epigenetic clocks, including considerations of study design, sample collection, and technical considerations for processing and interpreting epigenetic clocks. The goal of this review is to highlight some of the ways that epigenetic clocks can inform questions in human biology, and vice versa, and to provide human biologists with the foundational knowledge necessary to successfully incorporate epigenetic clocks into their research.

The Principle of Continuous Biological Information Flow as the Fundamental Foundation for the Biological Sciences. Implications for Ageing Research

“…These great achievements have been preceded by almost a decade of increasing involvement of epigenetic processes in ageing . This includes, among many more studies, the thriving field of epigenetic clock development (Liu et al, 2020;Ryan, 2020;Bell et al, 2019;Horvath, 2013;Bocklandt et al, 2011), and its relationship to all-cause mortality in humans (McCrory et al, 2020;Marioni et al, 2015). The relation between all-cause mortality and epigenetic clock signature suggests a somehow epigenetically caused mortality, as predicted by the model described in this paper.…”

Characteristics of epigenetic aging across gestational and perinatal tissues

“…This suggests that gestational epigenetic age acceleration or deceleration itself may not be linked to a higher risk for diseases per se, but that these associations are more complex and dependent on the condition and tissue during the earliest phase of life. It has been proposed that adjustments to the maturational tempo may explain why children in both favorable and unfavorable environments can exhibit epigenetic age acceleration, as this possibly constitutes specific adaptations to future challenges [53,54]. Recent studies in adult populations also reported large differences in associations with lifestyle risk factors among studies and clocks [14,55,56], and it was assumed that different epigenetic clocks may capture the consequences of different environmental stimuli [14].…”

“…Recent studies in adult populations also reported large differences in associations with lifestyle risk factors among studies and clocks [14,55,56], and it was assumed that different epigenetic clocks may capture the consequences of different environmental stimuli [14]. Overall, it has to be noted that the mechanistic underpinnings of biological age and epigenetic clocks are still discussed and not fully understood [3,19,54].…”

The Principle of Continuous Biological Information Flow as the Fundamental Foundation for the Biological Sciences. Implications for Ageing Research

“…These great achievements have been preceded by almost a decade of increasing involvement of epigenetic processes in ageing . This includes, among many more studies, the thriving field of epigenetic clock development (Liu et al, 2020;Ryan, 2020;Bell et al, 2019;Horvath, 2013;Bocklandt et al, 2011), and its relationship to all-cause mortality in humans (McCrory et al, 2020;Marioni et al, 2015). The relation between all-cause mortality and epigenetic clock signature suggests a somehow epigenetically caused mortality, as predicted by the model described in this paper.…”