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Research Paper|Volume 15, Issue 10|pp 3904—3938

DNAmFitAge: biological age indicator incorporating physical fitness

Kristen M. McGreevy1, Zsolt Radak2, Ferenc Torma2, Matyas Jokai2, Ake T. Lu3, Daniel W. Belsky4, Alexandra Binder5, Riccardo E. Marioni6, Luigi Ferrucci7, Ewelina Pośpiech8,9, Wojciech Branicki10, Andrzej Ossowski9, Aneta Sitek11, Magdalena Spólnicka12, Laura M. Raffield13, Alex P. Reiner14, Simon Cox15, Michael Kobor16, David L. Corcoran17, Steve Horvath1,3
  • 1Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 2Research Institute of Sport Science, University of Physical Education, Budapest, Hungary
  • 3San Diego Institute of Science, Altos Labs, San Diego, CA 92121, USA
  • 4Department of Epidemiology and Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY 10032, USA
  • 5Department of Cancer Epidemiology, University of Hawaii, Honolulu, HI 96813, USA
  • 6Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK
  • 7Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
  • 8Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland
  • 9Department of Forensic Genetics, Pomeranian Medical University in Szczecin, Szczecin, Poland
  • 10Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków, Poland
  • 11Department of Anthropology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
  • 12Central Forensic Laboratory of the Police, Warsaw, Poland
  • 13Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
  • 14Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
  • 15Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK
  • 16Department of Medical Genetics, University of British Columbia, Vancouver, Canada
  • 17Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
* Co-first authors
Received: July 12, 2022Accepted: January 23, 2023Published: February 22, 2023

Copyright: © 2023 McGreevy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Physical fitness is a well-known correlate of health and the aging process and DNA methylation (DNAm) data can capture aging via epigenetic clocks. However, current epigenetic clocks did not yet use measures of mobility, strength, lung, or endurance fitness in their construction. We develop blood-based DNAm biomarkers for fitness parameters gait speed (walking speed), maximum handgrip strength, forced expiratory volume in one second (FEV1), and maximal oxygen uptake (VO2max) which have modest correlation with fitness parameters in five large-scale validation datasets (average r between 0.16–0.48). We then use these DNAm fitness parameter biomarkers with DNAmGrimAge, a DNAm mortality risk estimate, to construct DNAmFitAge, a new biological age indicator that incorporates physical fitness. DNAmFitAge is associated with low-intermediate physical activity levels across validation datasets (p = 6.4E-13), and younger/fitter DNAmFitAge corresponds to stronger DNAm fitness parameters in both males and females. DNAmFitAge is lower (p = 0.046) and DNAmVO2max is higher (p = 0.023) in male body builders compared to controls. Physically fit people have a younger DNAmFitAge and experience better age-related outcomes: lower mortality risk (p = 7.2E-51), coronary heart disease risk (p = 2.6E-8), and increased disease-free status (p = 1.1E-7). These new DNAm biomarkers provide researchers a new method to incorporate physical fitness into epigenetic clocks.