Understanding heterogeneity of responses to, and optimizing clinical efficacy of, exercise training in older adults: NIH NIA Workshop summary

Abstract

Exercise is a cornerstone of preventive medicine and a promising strategy to intervene on the biology of aging. Variation in the response to exercise is a widely accepted concept that dates back to the 1980s with classic genetic studies identifying sequence variations as modifiers of the VO₂max response to training. Since that time, the literature of exercise response variance has been populated with retrospective analyses of existing datasets that are limited by a lack of statistical power from technical error of the measurements and small sample sizes, as well as diffuse outcomes, very few of which have included older adults. Prospective studies that are appropriately designed to interrogate exercise response variation in key outcomes identified a priori and inclusive of individuals over the age of 70 are long overdue. Understanding the underlying intrinsic (e.g., genetics and epigenetics) and extrinsic (e.g., medication use, diet, chronic disease) factors that determine robust versus poor responses to various exercise factors will be used to improve exercise prescription to target the pillars of aging and optimize the clinical efficacy of exercise training in older adults. This review summarizes the proceedings of the NIA-sponsored workshop entitled, "Understanding Heterogeneity of Responses to, and Optimizing Clinical Efficacy of, Exercise Training in Older Adults" and highlights the importance and current state of exercise response variation research, particularly in older adults, prevailing challenges, and future directions.

Keywords: Aging; Clinical efficacy; Exercise; Response variation.

Fig. 1

Schematic summarizing factors identified by the NIH NIA Workshop that contribute to exercise response variation in outcomes clinically relevant for older adults. Waterfall plot is a theoretical depiction of summary data from a controlled exercise training study. Each bar represents the delta (pre- to post-exercise training) from individual participants for a clinically relevant outcome modified by exercise training, and dashed lines represent technical error

Fig. 2

Summary of four (4) alternative study design strategies identified by the NIH NIA Workshop. A Pooled randomized controlled trials. B Multiphase optimization strategy (MOST). C Micro-randomized and SMART trials. D Personalized N-of-1 trials. These study designs may be adapted by researchers to better understand exercise response variation in aging populations