Molecular and cellular biology of the senescent hypertrophied and failing heart.
During aging, experimental studies have revealed various cellular changes, principal among which is myocyte hypertrophy, which compensates for the loss of myocytes and is associated with fibrosis. The expression of alpha-myosin heavy chain is replaced by that of the isogene beta-myosin, which leads to decreased myosin adenosine triphosphatase (ATPase) activity. In consequence, contraction is slower and more energetically economical. The Ca(2+)-ATPase of the sarcoplasmic reticulum and Na+/Ca2+ exchange activity are decreased, which probably explains the reduced velocity of relaxation. Membrane receptors are also modified, since the density of both the total beta-adrenergic and muscarinic receptors is decreased. The senescent heart is able to hypertrophy in response to overload and to adapt to the new requirements. Similar alterations are observed both in the senescent heart and in the overloaded heart, in clinical as well as in experimental studies; however, differences do exist, especially in terms of fibrosis and arrhythmias.
D000222:Adaptation, Physiological; D000251:Adenosine Triphosphatases / Q000235:genetics; D000375:Aging / Q000235:genetics / Q000473:pathology*; D001145:Arrhythmias, Cardiac / Q000209:etiology; D015220:Calcium Channels / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002303:Cardiac Output, Low / Q000235:genetics / Q000473:pathology*; D006332:Cardiomegaly / Q000235:genetics / Q000473:pathology*; D003585:Cell Biology; D004719:Endomyocardial Fibrosis / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D008967:Molecular Biology; D009200:Myocardial Contraction; D009206:Myocardium / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics; D009218:Myosins / Q000235:genetics; D011943:Receptors, Adrenergic, beta / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000378:metabolism
D015220:Calcium Channels; D011943:Receptors, Adrenergic, beta; D011976:Receptors, Muscarinic; D000251:Adenosine Triphosphatases; D018995:Myosin Heavy Chains; D009218:Myosins; D000252:Calcium-Transporting ATPases