Intrinsic and Extrinsic Contributors to the Cardiac Benefits of Exercise.

Among its many cardiovascular benefits, exercise training improves heart function and protects the heart against age-related decline, pathological stress, and injury. Here, we focus on cardiac benefits with an emphasis on more recent updates to our understanding. While the cardiomyocyte continues to play a central role as both a target and effector of exercise's benefits, there is a growing recognition of the important roles of other, noncardiomyocyte lineages and pathways, including some that lie outside the heart itself. We review what is known about mediators of exercise's benefits-both those intrinsic to the heart (at the level of cardiomyocytes, fibroblasts, or vascular cells) and those that are systemic (including metabolism, inflammation, the microbiome, and aging)-highlighting what is known about the molecular mechanisms responsible.

© 2024 The Authors.

This work was supported by the National Institutes of Health (R01AG061034 and R35HL155318 [to Dr Rosenzweig], R21AG077040 [to Dr Li], K08HL140200 [to Dr Rhee], T32HL007208 [to Dr Xia], and K76AG064328 [to Dr Roh]), the American Heart Association (20CDA35310184 [to Dr Li]), the German Research Foundation (grant number LE3257/1-1 [to Dr Lerchenmüller]), the Olympia Morata Fellowship and project support by the University of Heidelberg Medical Faculty (to Dr Lerchenmüller), the Else-Kröner-Fresenius-Stiftung (2019-A07 [to Dr Lerchenmüller]), the National Natural Science Foundation of China (82020108002 [to Dr Xiao] and 82200321 [to Dr Zhou]), and the Shanghai Sailing Program (21YF1413200 [to Dr Zhou]). All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.