Primary Submission Category: Applications in Health and Biology
The effect of long-term adherence to physical activity recommendations in midlife on plasma proteins associated with frailty in the Atherosclerosis Risk in Communities (ARIC) study
Authors: Fangyu Liu, Jennifer A. Schrack, Keenan A. Walker, Jeremy Walston, Rasika A. Mathias, Michael E. Griswold, Priya Palta, B. Gwen Windham, John W. Jackson,
Presenting Author: Fangyu Liu*
Clinical trials have shown favorable effects of exercise on frailty, supporting physical activity (PA) as a treatment and prevention strategy. However, less is known about the biological mechanisms underlying PA’s benefits. To date, proteomics studies that examined the effects of PA on proteins, some of which may function as molecules in the biological processes underlying frailty, have focused on structured exercise programs over a short term. To better understand the benefits of long-term, less structured PA in free living, we emulated a target trial that assigned 14,898 middle-aged adults to either (i) achieve and maintain the recommended PA level (≥150 minutes/week of moderate-to-vigorous physical activity [MVPA]) through 6 (+/-0.3) years of follow-up or (ii) follow a “natural course” strategy, where all individuals engage in their habitual MVPA. We estimated the population-level difference between (i) and (ii) on 45 previously identified frailty-associated proteins (standardized) at the end of the follow-up using inverse probability of weighting (IPW) and iterative conditional expectations (ICE). We found that long-term adherence to recommended MVPA improved the population levels of many frailty-associated proteins (ranging from 0.04 to 0.11 standard deviation); the greatest benefits were seen in proteins involved in the nervous system and inflammation. Sensitivity analyses suggested that the results were robust to unmeasured confounding and left truncation due to death.