Myocardial adaptations in advanced age.
Arterial stiffening and an increase in arterial pressure, particularly systolic, occur with advancing age in humans. The heart manifests left ventricular wall thickening and myocardial cell enlargement, which may be adaptations to these arterial changes. At the cellular level, studies in animal models indicate that the excitation-contraction coupling cycle is prolonged with aging. Specifically, a prolonged cystolic calcium transient enables prolonged force bearing capacity, an adaption permitting normal ejection of blood by the older heart into a stiff arterial tree. The changes in cellular Ca2+ cycling are regulated, in part at least, at the transcriptional level. Specifically, the density of Ca2+ pump sites of the sarcoplasmic reticulum is reduced, due to a down regulation of the gene coding for the sarcoplasmic reticulum Ca2+ pump, resulting in slower Ca2+ removal from the cytosole following excitation. During stress, a diminution in the increased heart rate and myocardial contractility occurs in healthy older humans, due in large measure to a postsynaptic reduction in the efficacy of beta adrenergic stimulation. At the cellular level in animal models, this is manifest by a relative failure of beta 1 adrenergic receptor stimulation to augment Ca2+ influx via L-type sarcolemmal Ca2+ channels and to augment the amplitude of the cytosolic Ca2+ transient. However, in situ a cardiac adaptation, i.e., cardiac dilatation, occurs during stress and maintains the stroke volume of the older heart. The above cardiovascular adaptations that occur in older healthy humans and animals occur at a younger age in the presence of chronic pressure overload.
Lakatta
E G
EG
Laboratory for Cardiovascular Science, National Institute on Aging, National Institutes of Health, Baltimore, Maryland.
D000222:Adaptation, Physiological / Q000502:physiology*; D000368:Aged; D000375:Aging / Q000502:physiology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004195:Disease Models, Animal; D006321:Heart / Q000033:anatomy & histology* / Q000502:physiology*; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D009200:Myocardial Contraction / Q000502:physiology; D051381:Rats
D002118:Calcium