Long-term caloric restriction improves mitochondrial and left ventricular function in senescent rats

Obesity and diabetes are common comorbid conditions among elderly patients undergoing coronary bypass surgery, causing increased perioperative complications. To improve this poor outcome, modifiable risk factors such as obesity should be targeted preoperatively. Therefore, an experimental study was undertaken to investigate the influence of weight loss on cardiac function in senescent rats.

Methods: Left ventricular (LV) samples were obtained from male young-adult (10 months) and senescent (28–30 months) Sprague-Dawley rats after 6 months of caloric restriction (–40%) or control-diet. LV function, mitochondrial respiratory function and the expression of apoptotic markers were measured.

Results: In control-fed senescent rats, LV function and mitochondrial function are depressed and expression of proapoptotic genes or procaspase activation are enhanced compared to young control animals. Transient (6 month) 40% caloric restriction results in a significant improvement in LV function and survival in senescent rats. This improvement in LV function is associated with a significant reduction in serum BNP (as a prognostic biomarker in heart failure) and with a decrease in proapoptotic activation of the myocardium. In contrast, however, LV function and mitochondrial function are not modified in young animals under the same diet regimen.

Conclusion: Basic mechanisms for cardioprotective effects of caloric restriction are preserved in the senescent heart and their activation results in an improvement of survival and LV function. Therefore, drugs activating these cardioprotective mechanisms of caloric restriction may yield a promising strategy to improve the outcome of obese, senescent patients undergoing coronary bypass surgery.