EFFECTS OF AGE ON C-FOS AND C-MYC GENE-EXPRESSION IN RESPONSE TO HEMODYNAMIC STRESS IN ISOLATED, PERFUSED RAT HEARTS

Using an ex vivo model we examined whether the age-associated modulation of proto-oncogene expression was due to the aging of the heart per se. In the two age groups of Wistar rats (2 and 18 months), expression of c-fos and c-myc genes was determined in isolated, isovolumically contracting hearts (balloon in the left ventricle) perfused with Tyrode's solution containing bovine serum and red blood cells. In both age groups, a c-fos signal was detected at 30 min, increased further at 60 min, and declined at 120 min, while the c-myc signal was detected at 60 min and increased for a further 120 min after initiation of perfusion at 25 mmHg of end-diastolic pressure (EDP). The expression of these genes by 60 min of relatively mild hemodynamic stress was depressed in old hearts compared to that in young hearts (c-fos at 0 (P < 0.05), 5 (P < 0.05) and 15 mmHg of EDP (P < 0.01); c-myc at 5 (P < 0.05) and 15 mmHg (P < 0.05). The age-associated differences in the expression of these genes were smaller under severe hemodynamic stress (25 mmHg of EDP). Peak systolic and diastolic wall stress calculated from left ventricular pressure, cavity volume and muscle weight were similar in the two age groups. Thus, aging diminished the expression of proto-oncogenes and seems to elevate the threshold at which hemodynamic stress to the heart results in a response at the gene level. The age-associated modulation is caused by aging of the heart per se. © 1993 Academic Press Limited.