Abstract 270: Long term Caloric Restriction and Myocardial Aging in Non Human Primates

Abstract

Caloric restriction (CR) has been shown to decrease aging and increase the lifespan of several model organisms. However, in two on-going independent, long-term CR studies in non-human primates (NHP) at the National Institute of Aging (NIA) and University of Wisconsin, Madison (UW) the outcome has been more complex. While CR monkeys in the UW study have experienced a significant increase in lifespan relative to their study controls, this was not the case for the NIA study. There, CR did not increase lifespan compared to the already long-lived controls. Yet, in both studies CR was associated with a decrease in the occurrence of age-related diseases. Left ventricle (LV) samples were provided from the rhesus monkeys from both studies to investigate the effect of long-term CR on myocardial pathology and aging in these two cohorts of non-human primates (NHPs). Although CR did not reduce cardiac fibrosis or hypertrophy in either study, there was a 5.9-fold increase in fibrosis (p<0.0001) in LV tissue from the UW study compared to NIA, irrespective of CR treatment. Myocardial mTOR levels were reduced with CR in the UW study, only. These findings indicate that the severity of cardiac fibrosis may not be susceptible to the mechanisms by which CR is affecting disease progression, and myocardial mTOR is apparently differently affected dependent on the study paradigm. Interestingly, the diet administered by the UW study contained a much higher sucrose content (28.5% sucrose by weight), compared to that of the NIA diet (3.9% sucrose by weight). This raises the intriguing possibility that myocardial fibrosis in NHPs may be driven by a high sucrose diet. Abbreviations: CR: Caloric Restriction NHP: Non-human primate mTOR: mechanistic Target of Rapamycin NIA: National Institute on Aging UW: University of Wisconsin, Madison