Abstract
Hypertension, atherosclerosis, and resultant chronic heart failure (HF) reach epidemic proportions among older persons, and the clinical manifestations and the prognoses of these worsen with increasing age. Thus, age per se is the major risk factor for cardiovascular disease. Changes in cardiac cell phenotype that occur with normal aging, as well as in HF associated with aging, include deficits in ß-adrenergic receptor (ß-AR) signaling, increased generation of reactive oxygen species (ROS), and altered excitation–contraction (EC) coupling that involves prolongation of the action potential (AP), intracellular Ca2+ (Ca 2+i ) transient and contraction, and blunted force- and relaxation-frequency responses. Evidence suggests that altered sarcoplasmic reticulum (SR) Ca2+ uptake, storage, and release play central role in these changes, which also involve sarcolemmal L-type Ca2+ channel (LCC), Na+–Ca2+ exchanger (NCX), and K+ channels. We review the age-associated changes in the expression and function of Ca2+ transporting proteins, and functional consequences of these changes at the cardiac myocyte and organ levels. We also review sexual dimorphism and self-renewal of the heart in the context of cardiac aging and HF.
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This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute on Aging.
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Janczewski, A.M., Lakatta, E.G. Modulation of sarcoplasmic reticulum Ca2+ cycling in systolic and diastolic heart failure associated with aging. Heart Fail Rev 15, 431–445 (2010). https://doi.org/10.1007/s10741-010-9167-5
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DOI: https://doi.org/10.1007/s10741-010-9167-5