DNA methylation aging clocks: challenges and recommendations

Author:

Bell Christopher G.ORCID,Lowe Robert,Adams Peter D.,Baccarelli Andrea A.,Beck Stephan,Bell Jordana T.,Christensen Brock C.,Gladyshev Vadim N.,Heijmans Bastiaan T.,Horvath Steve,Ideker Trey,Issa Jean-Pierre J.,Kelsey Karl T.,Marioni Riccardo E.,Reik Wolf,Relton Caroline L.,Schalkwyk Leonard C.,Teschendorff Andrew E.,Wagner Wolfgang,Zhang Kang,Rakyan Vardhman K.

Abstract

AbstractEpigenetic clocks comprise a set of CpG sites whose DNA methylation levels measure subject age. These clocks are acknowledged as a highly accurate molecular correlate of chronological age in humans and other vertebrates. Also, extensive research is aimed at their potential to quantify biological aging rates and test longevity or rejuvenating interventions. Here, we discuss key challenges to understand clock mechanisms and biomarker utility. This requires dissecting the drivers and regulators of age-related changes in single-cell, tissue- and disease-specific models, as well as exploring other epigenomic marks, longitudinal and diverse population studies, and non-human models. We also highlight important ethical issues in forensic age determination and predicting the trajectory of biological aging in an individual.

Funder

National Institute on Aging

National Cancer Institute

Glenn/AFAR

National Institutes of Health

National Institute for Health Research

UCLH Biomedical Research Centre

Economic and Social Research Council

Biotechnology and Biological Sciences Research Council

Nederlandse Hartstichting

Joint Programming Initiative A healthy diet for a healthy life

BBMRI-NL

National Institute of Environmental Health Sciences

AACR

Alzheimer’s Research UK

Medical Research Council

Cancer Research UK

National Science Foundation of China

Royal Society Newton Advanced Fellowship

Deutsche Forschungsgemeinschaft

Bundesministerium für Bildung und Forschung

Interdisciplinary Center for Clinical Research, RWTH Aachen University

Deutsche Krebshilfe

Publisher

Springer Science and Business Media LLC

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