Younger epigenetic age is associated with higher cardiorespiratory fitness in individuals with airflow limitation

Ana I Hernandez Cordero; Carli Peters; Xuan Li; Chen Xi Yang; Amirthagowri Ambalavanan; Julie L MacIsaac; Michael S Kobor; Gregory J Fonseca; Dany Doiron; Wan Tan; Jean Bourbeau; Dennis Jensen; Don D Sin; Graeme J Koelwyn; Michael K Stickland; Qingling Duan; Janice M Leung; CanCOLD Collaborative Research Group

doi:10.1016/j.isci.2024.110934

Younger epigenetic age is associated with higher cardiorespiratory fitness in individuals with airflow limitation

iScience. 2024 Sep 13;27(10):110934. doi: 10.1016/j.isci.2024.110934. eCollection 2024 Oct 18.

Authors

Ana I Hernandez Cordero^{1

2}, Carli Peters¹, Xuan Li¹, Chen Xi Yang¹, Amirthagowri Ambalavanan³, Julie L MacIsaac^{2

4}, Michael S Kobor^{2

4}, Gregory J Fonseca⁵, Dany Doiron⁵, Wan Tan¹, Jean Bourbeau⁵, Dennis Jensen^{5

6}, Don D Sin^{1

2

7}, Graeme J Koelwyn^{1

8}, Michael K Stickland⁹, Qingling Duan³, Janice M Leung^{1

2}; CanCOLD Collaborative Research Group

Affiliations

¹ Centre for Heart Lung Innovation, St. Paul's Hospital and University of British Columbia, Vancouver, Canada.
² Edwin S. H. Leong Healthy Aging Program, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
³ Department of Biomedical and Molecular Sciences, School of Medicine, and School of Computing, Queen's University, Kingston, Canada.
⁴ Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, Canada.
⁵ McGill University Health Centre, McGill University, Montreal, Canada.
⁶ Clinical Exercise & Respiratory Physiology Laboratory, Department of Kinesiology and Physical Education, Faculty of Education, McGill University, Montreal, Canada.
⁷ Division of Respiratory Medicine, Department of Medicine, University of British Columbia, Vancouver, Canada.
⁸ Faculty of Health Sciences, Simon Fraser University, Burnaby, Canada.
⁹ Division of Pulmonary Medicine, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Canada.

Abstract

We hypothesized that increased cardiorespiratory fitness (CRF) slows down a person's aging, particularly in individuals with chronic airflow limitation (CAL). Participants aged ≥40 years (n = 78) had baseline blood DNA methylation profiled and underwent cardiopulmonary cycle exercise testing at baseline and at three years. Epigenetic clocks were calculated and tested for their association with CRF using linear regression. Differentially methylated genes associated with CRF were identified using a robust linear model. Higher CRF at baseline was associated with lower age acceleration in the epigenetic clocks DNAmAgeSkinBlood (p = 0.016), DNAmGrimAge (p = 0.012), and DNAmGrimAge2 (p = 0.011). These effects were consistent in individuals with CAL (DNAmGrimAge p = 0.009 and DNAmGrimAge2 p = 0.007). CRF at three years was associated with baseline DNAmGrimAge (p = 0.015) and DNAmGrimAge2 (p = 0.011). Differentially methylated genes associated with CRF enriched multiple aging-related pathways, including cellular senescence. Enhancing CRF may be one intervention that can slow biological aging and improve health outcomes in chronic respiratory diseases.

Keywords: Cardiovascular medicine; Kinesiology; Respiratory medicine.