Effects of Caloric Restriction on Cardiac Oxidative Stress and Mitochondrial Bioenergetics: Potential Role of Cardiac Sirtuins

Abstract

The biology of aging has not been fully clarified, but the free radical theory of aging is one of the strongest aging theories proposed to date. The free radical theory has been expanded to the oxidative stress theory, in which mitochondria play a central role in the development of the aging process because of their critical roles in bioenergetics, oxidant production, and regulation of cell death. A decline in cardiac mitochondrial function associated with the accumulation of oxidative damage might be responsible, at least in part, for the decline in cardiac performance with age. In contrast, lifelong caloric restriction can attenuate functional decline with age, delay the onset of morbidity, and extend lifespan in various species. The effect of caloric restriction appears to be related to a reduction in cellular damage induced by reactive oxygen species. There is increasing evidence that sirtuins play an essential role in the reduction of mitochondrial oxidative stress during caloric restriction. We speculate that cardiac sirtuins attenuate the accumulation of oxidative damage associated with age by modifying specific mitochondrial proteins posttranscriptionally. Therefore, the distinct role of each sirtuin in the heart subjected to caloric restriction should be clarified to translate sirtuin biology into clinical practice.

Mitochondrial Metabolism in Aging Heart

“…219 CR can improve mitochondrial bioenergetics through reduction of oxidative stress and activation of sirtutins. 220 Resveratrol supplementation also provides benefit in delaying aging-mediated cardiovascular dysfunction. CR, exercise, and resveratrol all activate sirtuin 1 and 3.…”

Oxidative Stress in Aging-Matters of the Heart and Mind

“…This activation also is anti-inflammatory [162]. There is also a potential role for the sirtuins (SIRT1, 3, 4, 5) involvement in reducing the impact of oxidative damage in post-translationally modified mitochondrial proteins, although the mechanism is unclear [163]. SIRT1 in particular, has been shown to reduce accumulation of Aβ in AD [164].…”

Tumor Dormancy, Quiescence, and Senescence, Vol. 3

“…These events all negatively affect mitochondrial and cellular function and contribute to the decline in cardiac function with aging (Shinmura 2013 ). An age-related increase in oxidative damage has been well documented.…”

“…As mentioned above, cardiomyocyte removal via apoptosis increases with aging (Centurione et al 2002 ;Kajstura et al 2010 ); however, it is still unclear if autophagic failure is directly attributable to the increased apoptosis in the aged heart. Regardless of this issue, mitochondrial dysfunction is likely to play a pivotal role in cardiac senescence (Shinmura 2013 ). Mitochondrial dysfunction is also implicated in the pathogenesis of a host of CVD that are highly prevalent in old age, including coronary artery disease, CHF, LVH, and diabetic cardiomyopathy (Dutta et al 2012 ).…”