TY - JOUR
T1 - DNAmFitAge
T2 - Biological age indicator incorporating physical fitness
AU - Mcgreevy, Kristen M.
AU - Radak, Zsolt
AU - Torma, Ferenc
AU - Jokai, Matyas
AU - Lu, Ake T.
AU - Belsky, Daniel W.
AU - Binder, Alexandra
AU - Marioni, Riccardo E.
AU - Ferrucci, Luigi
AU - Pośpiech, Ewelina
AU - Branicki, Wojciech
AU - Ossowski, Andrzej
AU - Sitek, Aneta
AU - Spólnicka, Magdalena
AU - Raffield, Laura M.
AU - Reiner, Alex P.
AU - Cox, Simon
AU - Kobor, Michael
AU - Corcoran, David L.
AU - Horvath, Steve
N1 - Funding: SH, KMM, REM, and ATL supported from 1U01AG060908. ZR, FT, and MJ supported from the National Excellence Program (126823), Scientific Excellence Program, TKP2020-NKA-17. REM: Alzheimer’s Society AS-PG-19b-010. SRC: Sir Henry Dale Fellowship by Wellcome Trust and Royal Society grant 221890/Z/20/Z.
FHS is funded by National Institute of Health (NIH) contract N01-HC-25195 and HHSN268201500001I. The laboratory and analytical work: the Division of Intramural Research, National Heart, Lung, and Blood Institute (NHLBI), NIH. The analytical component was also funded by the Center for Information Technology, NIH.
The Jackson Heart Study (JHS) is supported and conducted in collaboration with Jackson State University (HHSN268201800013I), Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I) and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I and HHSN268201800012I) contracts from the National Heart, Lung, and Blood Institute (NHLBI) and the National Institute on Minority Health and Health Disparities (NIMHD). The authors also wish to thank the staffs and participants of the JHS.
The views expressed in this manuscript are those of the authors and do not necessarily represent the views of the National Heart, Lung, and Blood Institute; the National Institutes of Health; or the U.S. Department of Health and Human Services.
WHI program is funded by the NHLBI, and the U.S. Department of Health and Human Services through contracts HHSN268201600018C, HHSN268201600001C, HHSN268201600002C, HHSN268201600003C, and HHSN268201600004C.
The LBC1921 was supported by the UK’s Biotechnology and Biological Sciences Research Council. The LBC1936 is supported by Age UK, the Medical Research Council (G0701120, G1001245, MR/M013111/1, MR/R024065/1), and the University of Edinburgh. Methylation typing was supported by Centre for Cognitive Ageing and Cognitive Epidemiology (Pilot Fund award), Age UK, The Wellcome Trust Institutional Strategic Support Fund, The University of Edinburgh, and The University of Queensland.
CALERIE was conducted in collaboration with Columbia University Mailman School of Public Health with support from National Institute on Aging grants R01AG061378 and R33AG070455.
Research on the Polish Study is financed by the National Centre for Research and Development (NCBR) in Poland within the framework of call 10/2019 related to scientific research and studies for national defense and security [project no. DOB-BIO10/06/2019].
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
U2 - 10.18632/aging.204538
DO - 10.18632/aging.204538
M3 - Article
SN - 1945-4589
VL - 15
JO - Aging
JF - Aging
ER -