Effects of Aging and Exercise Training on Mitochondrial-Mediated Apoptosis in the Rat Heart

초록

We used 3-month and 24-month old Fischer-344 rats as our young and old groups, respectively. One-half of the rats in each group ran on a treadmill at 15 m/min up a 15 incline, one hour/day, 5 days/week for 12 weeks (n=10 in each group): young sedentary controls (YS), young exercise trained (YE), old sedentary controls (OS), and old exercise trained (OE). We observed dramatic remodeling (e.g., decrease in myocyte number/area, enlargement of remaining cardiomyocytes, and increased connective tissue) from the old sedentary rats compared with those from the young sedentary rats. However, 12 weeks exercise training provided significant protection against myocyte reduction and remodeling in the aging heart. We found that aging significantly increased histone-associated DNA fragmentation (apoptosis marker) in the left ventricle in OS compared with YS. In contrast, exercise training attenuated DNA fragmentation in the left ventricle in OE compared with OS. Similarly, left ventricles from OS displayed a higher incidence (3.32%) of TUNEL+ nuclei (another apoptosis marker). However, exercise training greatly reduced TUNEL+ nuclei (1.62%) in OE, indicating that exercise training ameliorates apoptosis in the aging heart. Caspase-3 integrates apoptotic signaling from mitochondrial Bcl-2 family pathway, cytokine/Fas pathway, and ER/Ca2+ pathway. Cleaved (activated) caspase-3 protein levels were dramatically higher (+123%) in the left ventricle of OS compared with YS. However, exercise training significantly decreased (-33%) cleaved caspase-3 protein levels in the old hearts. We found that aging increased (+89%) protein levels of procaspase-9 in the rat left ventricle, and exercise training resulted in a significant decrease (-74%) of procaspase-9 protein levels in the old rat hearts. Protein levels of pro-apoptotic Bax in the left ventricle was dramatically higher (+176%) in OS compared with YS. In contrast, exercise training resulted in a significant decrease (