Mechanisms of Exercise-Induced Cardiac Remodeling Differ Between Young and Aged Hearts

Emily E. Schmitt; Benjamin D. McNair; Sydney M. Polson; Ross F. Cook; Danielle R. Bruns

Disclosures

Exerc Sport Sci Rev. 2022;50(3):137-144. 

In This Article

The Aging Heart

Before discussion of the aging heart and exercise can occur, a definition of age must be reached. Clinically, aging refers to humans 65 yr and older as defined by the Centers for Disease Control and Prevention and World Health Organization. In preclinical models, this roughly extrapolates to 18 months in mice (Jackson Laboratory) and 24 months in rats.[4] We note that some contention still exists with regard to these definitions, specifically with respect to chronological versus biological age and factors such as frailty and comorbidities. However, for the purposes of this review, our analysis has been restricted to clinical and preclinical reports, which meet these definitions. We also note for the purposes of this review that we have limited our discussion to healthy models, meaning those free from overt cardiovascular disease. However, given the strong correlation between sedentary behavior, aging, and chronic disease, it is likely that the definition of healthy falls on a spectrum of conditions from confirmed healthy to those with undiagnosed occult disease.

The heart undergoes several physiological and molecular changes with aging, many of which are beyond the scope of the current review. Here, we focus on several well-reported changes, which is discussed in the context of exercise. Even in the absence of factors that adversely impact cardiac function (i.e., diabetes, hypertension), the heart remodels with advanced age. Morphologically, the aging heart is characterized by left ventricular (LV) hypertrophy[5] and elevated deposition of extracellular matrix (ECM) proteins.[6] Longitudinal observations from the Framingham Heart Study report age-associated increases in LV wall thickness and decreased LV dimensions[7] across the adult life course, along with increases in myocyte cell size.[8] Autopsies of human hearts demonstrate higher collagen content in individuals older than 65 yr compared with 20- to 25-yr-olds, even in subjects without overt cardiac disease.[6] These changes to cardiac morphology are also noted in aging rodents, with aged mice and rats demonstrating elevated LV chamber size, wall thickness, and hypertrophy alongside higher LV collagen content.[9,10] As a result of, or at least in parallel to these morphometric changes, the heart also undergoes changes in cardiac function with advanced age. The aging heart demonstrates diastolic dysfunction with impaired relaxation. Although systolic function is not typically impaired at rest, in response to increased cardiac work such as during exercise, the aged heart displays a diminished ability to improve cardiac inotropic and chronotropic reserve.[7,9] Together, these changes result in reduced cardiovascular and cardiorespiratory function and elevated risk for heart disease.

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