Age-related changes before and after imposition of hemodynamic stress in the mammalian heart.

This review focusses on the following issues: how the mammalian heart grows and ages; age-related changes in the mammalian heart before and after imposition of hemodynamic stress; and antiaging modulation in the mammalian heart. The heart and other organs grow and age together in the whole body, and interactions occur between these organs. Therefore, the age-related changes at the molecular and cellular level in the in vivo heart are the summation of the changes of the heart per se and the effects of other organs or tissues on the heart. Furthermore, myocytes grow and age under the influence of age-related changes in other myocytes and other types of cells in the myocardial tissue through autocrine or paracrine mechanisms, because myocytes are exposed to many biologically active substances which are released from those cells. Since hypertension and ischemia are very common hemodynamic events in aged hearts, the characteristics in aged hearts are discussed in terms of responses to hypertension or ischemia. The induction of proto-oncogenes and heat shock protein genes in response to milder hemodynamic stress such as pressure-overload and ischemia is diminished in aged hearts. However, the aged heart can respond to more severe stress to a level similar to that of young-adult hearts. Therefore, the senescent heart is characterized by its attenuated adaptation to hemodynamic stress and by its ability to adapt to limited environmental changes. Several interventions have antiaging effects on the heart at the molecular and cellular level.