Cellular basis of aging in the mammalian heart

This review is concerned with the functional and structural changes occurring in the aging heart. These changes were investigated in an integrated fashion in Fischer 344 rats at 4, 12, 20, and 29 months after birth. Mean arterial pressure, left ventricular systolic and end-diastolic pressures, as well as stroke volume remained substantially constant up to 20 months. At 29 months, however, end-diastolic pressure was significantly increased, and dP/dt and stroke volume were depressed. Focal areas of interstitial and replacement fibrosis were markedly increased at 20 and 29 months, mostly in the subendocardial region of the ventricular wall. Also the aggregate number of mononucleated and binucleated cells in the left ventricle as a function of age was determined. The number of mononucleated cells increased up to 20 months but decreased thereafter; the binucleated cells showed a reversed pattern. The aging process of the heart involves a number of interrelated events including biochemical, electrical, mechanical and structural modifications. With aging and senescence, left ventricular failure develops in the Fischer rat model, and a similar process may occur in the human as well.