Changes in the heart that accompany advancing age: Humans to molecules

Age per se is the major risk factor for cardiovascular disease. Elucidation of the age-associated alterations in cardiac and arterial structure and function at both the cellular and molecular levels provides valuable clues that may assist in the development of effective therapies to prevent, to delay, or to attenuate the cardiovascular changes that accompany aging and contribute to the clinical manifestations of chronic heart failure. Changes in cardiac cell phenotype that occur with normal aging, as well as in HF associated with aging, include deficits in β-adrenergic receptor (β-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⁺ (Cai ²⁺) 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. In spite of the interest in the physiology of the age-associated changes in cardiovascular structure and function, however, cardiovascular aging has remained, for the most part, outside of mainstream clinical medicine. This is largely because the pathophysiologic implications of these age-associated changes are largely underappreciated and are not well disseminated in the medical community. In fact, age has traditionally been considered a nonmodifiable risk factor. Policy makers, researchers, and clinicians need to intensify their efforts toward identification of novel pathways that could be targeted for interventions aiming at retardation or attenuation of these age-associated alterations that occur in the heart and arteries, particularly in individuals in whom these alterations are accelerated. Translational studies would then examine whether these strategies (i.e., those targeting cardiovascular aging) can have a salutary impact on the adverse cardiovascular effects of accelerated cardiovascular aging. As such, cardiovascular aging is a promising frontier in preventive cardiology.