Exercise and Sirtuins: A Way to Mitochondrial Health in Skeletal Muscle

Abstract

The sirtuins form a family of evolutionarily conserved nicotinamide adenine dinucleotide (NAD)-dependent deacetylases. Seven sirtuins (SIRT1–SIRT7) have been described in mammals, with specific intracellular localization and biological functions associated with mitochondrial energy homeostasis, antioxidant activity, proliferation and DNA repair. Physical exercise affects the expression of sirtuin in skeletal muscle, regulating changes in mitochondrial biogenesis, oxidative metabolism and the cellular antioxidant system. In this context, sirtuin 1 and sirtuin 3 have been the most studied. This review focuses on the effects of different types of exercise on these sirtuins, the molecular pathways involved and the biological effect that is caused mainly in healthy subjects. The reported findings suggest that an acute load of exercise activates SIRT1, which in turn activates biogenesis and mitochondrial oxidative capacity. Additionally, several sessions of exercise (training) activates SIRT1 and also SIRT3 that, together with the biogenesis and mitochondrial oxidative function, jointly activate ATP production and the mitochondrial antioxidant function.

Regulation of Nrf2 by Mitochondrial Reactive Oxygen Species in Physiology and Pathology

“…Mitochondrial biogenesis is also induced by physical exercise [59,60] and has been proposed to extend lifespan, at least in part, by activating the same pathways [3]. Increased NAD + /NADH also activates the mitochondrially localized family member SIRT3, which up-regulates ATP synthesis by activating enzymes in the TCA cycle, ETC and fatty acid oxidation and contributes to antioxidant defense by SOD2 induction via FoxO1 deacetylation [61] (Figure 2). Mitochondrial unfolded protein response (UPR MT ) is also thought as a mitohormetic machinery [62].…”

“…An increase in AMP/ATP activates AMPK, which induces mitochondrial biogenesis via PGC1α activation and enhances autophagy via mTOR inhibition. An increase in NAD + /NADH activates the NAD + -dependent deacetylases SIRT1 and SIRT3 [61]. Mitochondrially localized SIRT3 activates enzymes involved in mitochondrial ATP synthesis, whereas nuclear SIRT1 also activates PGC1α [50,55].…”

Impact of Nutrition on Short-Term Exercise-Induced Sirtuin Regulation: Vegans Differ from Omnivores and Lacto-Ovo Vegetarians

“…SIRT3 activates complex 1 [26,27], complex 2 [28], complex 3 [27], complex 4 [29], and complex 5 [30] of the respiratory chain. Mitochondrial biogenesis during exercise is regulated by SIRT3 [31] as well as SIRT1 [32]. In addition, SIRT1 stimulates mitochondrial biogenesis and oxidative phosphorylation via PGC-1α (Peroxisome proliferator-activated receptor gamma coactivator 1-alpha) [33], while fatty acid oxidation is inhibited by SIRT4 [34].…”

“…In recent years, exercise has been shown to activate sirtuins, namely SIRT1 and SIRT3 [32]. Furthermore, an investigation by Villanova and colleagues showed that sirtuin activity might be upregulated by physical exercise [39].…”

Role of Sirt3 in Differential Sex-Related Responses to a High-Fat Diet in Mice

“…The excessive production of ROS leads to oxidative stress, a crucial event that contributes to mitochondrial dysfunction and age-related pathologies [12]. Sirt3 plays a role in preventing metabolic syndrome [10], and is found to be upregulated in response to caloric restriction and exercise [13], while being downregulated with age, upon an HFD, and in diabetes [14]. Sirt3 is dispensable at a young age under homeostatic conditions but is essential under stress conditions or at an old age, making it a potential regulator of aging process.…”