Acute and chronic adaptation to hemodynamic overload and ischemia in the aged heart

Congestive heart failure occurs more frequently in older individuals. This higher incidence of heart failure may be caused by the diminished capacity of aged hearts to adapt to increased hemodynamic overload and ischemia which are the most important triggers for heart failure in the aged. In the immediate early phase after the imposition of ascending aortic banding, the mRNA expression of proto-oncogenes (c-fos, c-jun and c-myc) was diminished in aged rat hearts compared with young adult hearts. In the later phase, the pattern of expression of contractile protein genes in aged hearts differed quantitatively from that in adult hearts. The hypertrophic responses to the imposition of not only pressure-overload but also volume-overload were also diminished at the organ and cellular levels. In addition, this diminution was observed both in the left and right ventricles. Against ischemic insults, aged hearts responded with a diminished expression of proto-oncogenes and heat shock proteins. Thus, aged hearts are characterized by poor adaptation to hemodynamic overload and by a poor self-protective mechanism against cell death through necrosis and apoptosis. Of interest, more severe hemodynamic overload elevated the diminished responses to a level similar to that in adult hearts, suggesting that the threshold for the heart to respond to hemodynamic overload or ischemia is elevated in aged hearts. In addition, even in aged hearts ischemic preconditioning upregulated the diminished gene expression in a gene-dependent manner. Thus, the capacity for adaptation to hemodynamic overload and ischemia is diminished in aged hearts, but aged hearts preserve the ability to respond to these under some conditions.