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, ,

  • 1 Department of Biostatistics, Fielding School of Public Health, University of California Los Angeles, Los Angeles, CA 90095, USA
  • 2 Research Institute of Sport Science, University of Physical Education, Budapest, Hungary
  • 3 San Diego Institute of Science, Altos Labs, San Diego, CA 92121, USA
  • 4 Department of Epidemiology and Butler Columbia Aging Center, Columbia University Mailman School of Public Health, New York, NY 10032, USA
  • 5 Department of Cancer Epidemiology, University of Hawaii, Honolulu, HI 96813, USA
  • 6 Centre for Genomic and Experimental Medicine, Institute of Genetics and Cancer, University of Edinburgh, Edinburgh EH4 2XU, UK
  • 7 Longitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA
  • 8 Małopolska Centre of Biotechnology, Jagiellonian University, Kraków, Poland
  • 9 Department of Forensic Genetics, Pomeranian Medical University in Szczecin, Szczecin, Poland
  • 10 Institute of Zoology and Biomedical Research, Faculty of Biology, Jagiellonian University, Kraków, Poland
  • 11 Department of Anthropology, Faculty of Biology and Environmental Protection, University of Łódź, Łódź, Poland
  • 12 Central Forensic Laboratory of the Police, Warsaw, Poland
  • 13 Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
  • 14 Department of Epidemiology, University of Washington, Seattle, WA 98195, USA
  • 15 Lothian Birth Cohorts, Department of Psychology, University of Edinburgh, Edinburgh EH8 9JZ, UK
  • 16 Department of Medical Genetics, University of British Columbia, Vancouver, Canada
  • 17 Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
* Co-first authors

Received: July 12, 2022       Accepted: January 23, 2023       Published: February 22, 2023
How to Cite

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.


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.


DNAm: DNA methylation; FEV: forced expiratory volume; FEV1: forced expiratory volume in one second; VO2max: maximal oxygen uptake; Gripmax: maximum handgrip force; FHS: Framingham Heart Study Offspring Cohort; BLSA: Baltimore Longitudinal Study on Aging; LBC1921: Lothian Birth Cohort 1921; LBC1936: Lothian Birth Cohort 1936; CALERIE: Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy; JHS: Jackson Heart Study; WHI: Women’s Health Initiative; CpG: cytosine-phosphate-guanine; CHD: time-to-coronary-heart-disease; OR: odds ratios; GREAT: Genomic Regions Enrichment of Annotations Tool; FDR: false discovery rate.