The Role of Exercise in Cardiac Aging: From Physiology to Molecular Mechanisms

Abstract

Aging induces structural and functional changes in the heart that are associated with increased risk of cardiovascular disease and impaired functional capacity in the elderly. Exercise is a diagnostic and therapeutic tool, with the potential to provide insights into clinical diagnosis and prognosis, as well as the molecular mechanisms by which aging influences cardiac physiology and function. In this review, we first provide an overview of how aging impacts the cardiac response to exercise, and the implications this has for functional capacity in older adults. We then review the underlying molecular mechanisms by which cardiac aging contributes to exercise intolerance, and conversely how exercise training can potentially modulate aging phenotypes in the heart. Finally, we highlight the potential use of these exercise models to complement models of disease in efforts to uncover new therapeutic targets to prevent or treat heart disease in the aging population.

Keywords: aging; cardiovascular diseases; exercise; heart; phenotype.

Figure 1

Multiple mechanisms have been proposed for the impaired cardiomyocyte function observed in aging, and how exercise partially reverses their effects. (1) Diminished cardiac performance in the pathological hypertrophy of aging is linked to decreased IGF1-PI3K-AKT and bAR-cAMP-PKA signaling, decreased SERCA expression and activity and inefficient calcium handling, and mitochondrial dysfunction secondary to excessive ROS. (2) Exercise confers physiological hypertrophy and cardio-protection in the form of enhanced beta-adrenergic and IGF1 signaling, SERCA activity and calcium handling, and mitochondrial dynamics, the latter mediated largely through PGC-1a. (3) These benefits of exercise mitigate the effects of aging (Illustration Credit: Ben Smith).