Calorie restriction can reverse, as well as prevent, aging cardiomyopathy

Abstract

Calorie restriction (CR) is the most widely studied intervention protecting from the adverse effects of aging. Almost all prior studies have examined the effects of CR initiated in young animals. Studies examining the effects of CR on development of aging cardiomyopathy found only partial prevention. The major goal of this study was to determine whether CR initiated after aging cardiomyopathy developed could reverse the cardiomyopathy. Aging cardiomyopathy in 2-year-old mice was characterized by reduced left ventricular (LV) function, cardiac hypertrophy, and increased cardiac apoptosis and fibrosis. When short-term (2 months) CR was initiated after aging cardiomyopathy developed in 20-month-old mice, the decrease in cardiac function, and increases in LV weight, myocardial fibrosis and apoptosis were reversed, such that the aging hearts in these mice were indistinguishable from those of young mice or mice where CR was initiated in young mice. If apoptosis was the mechanism for protecting against aging cardiomyopathy, then total myocyte numbers should have reverted to normal with CR, but did not. However, the alterations in cytoskeletal proteins, which contribute to aging cardiomyopathy, were no longer observed with CR. This is the first study to demonstrate complete prevention of aging cardiomyopathy by CR and, more importantly, that instituting this intervention even later in life can rapidly correct aging cardiomyopathy, which could have important therapeutic implications.

Protein and Mitochondria Quality Control Mechanisms and Cardiac Aging

“…Caloric restriction (CR), defined as the reduction of calorie intake without malnutrition, is the most reproducible dietary intervention known to promote health and lifespan among model organisms [157]. CR stimulates cardiac autophagy to a greater extent in older vs. younger rodents and humans [122,[158][159][160][161]. The clinical relevance of this strategy is uncertain, however, because strict compliance/self-discipline is required.…”

Calorie restriction in rodents: Caveats to consider

“…For example, Yan et al initiated a 2-mo CR regimen in 20-mo old mice, an age at which distinctive cardiomyopathy is observed (Yan et al, 2013). CR-treated mice showed cardiac function equivalent to young mice as well as reduced myocardial fibrosis and apoptosis.…”

Cardiac fibrosis in the ageing heart: Contributors and mechanisms

“…Furthermore, obesity and/or metabolic syndromes in older persons may also induce progressive changes in myocardial inflammation, apoptosis and fibrosis which involves the activation of mTOR signalling and depression of autophagy . Calorie restriction may exert a cardiac protective effect by attenuation of mitochondrial ROS production, activate autophagy and inhibit inflammatory signalling pathways . Restoring autophagy in the ageing heart may be a potential strategy for treating ageing‐related cardiac fibrosis in the future.…”