Exercise training restores IGFIR survival signaling in d-galactose induced-aging rats to suppress cardiac apoptosis.

INTRODUCTION

Insulin-like growth factor-I receptor (IGF1R) mediated survival signaling is a crucial mechanism for cellular endurance and a potential indicator of recuperation in deteriorating hearts.

OBJECTIVE

This study evaluates the impact of long-term exercise training in enhancing cardiac survival mechanism in D-galactose-induced toxicity associated aging rats.

METHODS

Forty-eight male SD-rats were segregated into 4 groups (n=9) and were named as control, exercise training groups, aging group and aging group with exercise training. Aging was induced by intraperitoneal (IP) D-galactose (150 mL/kg) injection for 8 weeks and for exercise training, the rats were left to swim in warm water for 60 min every day and 5 times/week. Western blotting of proteins from the left ventricles was performed to identify the modulations in the survival signaling. Tissue sections were analyzed to determine the extent of fibrosis and apoptosis.

RESULTS

Western-blot analysis performed on the excised left ventricles (LV) showed that proteins of the cardiac survival pathway including IGF1R and Akt and the pro-survival Bcl-2 showed significant decrease in the aging group, whereas the levels were restored in the aging rats subjected to exercise training. In addition, aging groups showed increased interstitial space and collagen accumulation. Further, TUNEL assay showed higher number of apoptotic cells in the LV of aging group, which was correlated with increase in the proteins involved in FAS-FADD-dependent apoptosis. However, these aging associated effects were ameliorated upon exercise training in the D-galactose-induced aging rats that showed elevated IGF1R/Akt signaling.

CONCLUSION

The results suggest that IGFIR survival signaling cascadeis elevated in following long-term exercise training and thereby provide cardio-protective benefits in D-galactose induced aging rats.