The Ischemic Heart

Abstract

Caloric restriction has emerged as an effective strategy for lengthening lifespan in a variety of species.1 In mammals, one mechanism for this phenomenon may be the prevention of detrimental age-related alterations in cellular function1 and presumably subsequent improvement in organ function. The effects of caloric restriction on the heart, at least in rats and mice, involve a number of changes in gene expression that are beneficial to the aged cardiomyocyte2 and/or protect the heart from ischemic injury.3 Although it is likely that all of the beneficial mediators of caloric restriction have not been identified, a number of proteins in the mammalian sirtuin family may play key roles in the regulation of health and longevity.4 In addition, recent evidence has suggested that alterations in whole-body energy metabolism contribute to the beneficial effects of caloric restriction.5 Indeed, caloric restriction in mammals leads to loss of adipose tissue and dramatically alters the action of this endocrine organ.6 As such, caloric restriction contributes to changes in adipose tissue–derived hormone (adipokine) secretion, which can govern whole-body metabolism.7 Furthermore, studies using isolated cardiac myocytes suggest that these adipokines may exert direct end-organ effects that are independent from alterations in whole-body metabolism.8–10 One adipokine that is significantly increased during caloric restriction is adiponectin.11 Previous work has shown that adiponectin exerts a host of protective effects on the cardiovascular system12 and as such may be an essential component mediating the effects of caloric restriction. Article p 2809 The focus on adiponectin in the cardiovascular system has been due largely to the fact that in humans, circulating adiponectin levels are negatively correlated with increased body mass index.13 Because increased body mass index is associated with a number of obesity-linked disorders, including cardiovascular disease, the reduction in serum …