zwar schon aus 2010, enthält somit nichts neues, aber nett zusammengefasst in der Introduction:
Recent evidence points to a strong relationship between increased mitochondrial biogenesis and increased survival in eukaryotes. Branched-chain amino acids (BCAAs) have been shown to extend chronological life span in yeast. However, the role of these amino acids in mitochondrial biogenesis and longevity in mammals is unknown. Here, we show that a BCAA-enriched mixture (BCAAem) increased the average life span of mice. BCAAem supplementation increased mitochondrial biogenesis and sirtuin 1 expression in primary cardiac and skeletal myocytes and in cardiac and skeletal muscle, but not in adipose tissue and liver of middle-aged mice, and this was accompanied by enhanced physical endurance. Moreover, the reactive oxygen species (ROS) defense system genes were upregulated, and ROS production was reduced by BCAAem supplementation. All of the BCAAem-mediated effects were strongly attenuated in endothelial nitric oxide synthase null mutant mice. These data reveal an important antiaging role of BCAAs mediated by mitochondrial biogenesis in mammals.
Aging is a natural process that affects most biological functions and results in reduced resistance to stress, increased vulnerability to diseases (including cardiovascular disease, cancer, diabetes, sarcopenia, osteoporosis, and kidney disease), and increased probability of death. Among the plethora of biological phenomena affected by aging, the malfunction of mitochondria and the decrease of mitochondrial biogenesis, together with increased oxidative damage, seem to exert some of the most deleterious effects on the organism (Guarente, 2008 and López-Lluch et al., 2008). A variety of strategies that alleviate age-related deficits in mitochondrial biogenesis and activity, including calorie restriction (CR) and moderate physical exercise, promote survival in mammals. These interventions increase the expression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α, a master regulator of mitochondrial biogenesis and reactive oxygen species [ROS] defense system) and of sirtuin 1 (SIRT1, a member of the sirtuin family linked to life span extension, enhanced mitochondrial biogenesis, and decreased ROS production), thus reducing oxidative damage in metabolically active tissues of mice and humans (Civitarese et al., 2007, Nisoli et al., 2005 and Ristow et al., 2009). The CR effects on mitochondrial biogenesis are due, at least in part, to induction of endothelial nitric oxide synthase (eNOS) expression (Nisoli et al., 2005). Indeed, eNOS null mutant (eNOS−/−) mice are characterized by a reduced life span (Li et al., 2004), due to age-related diseases (Cook et al., 2003), and by a reduced mitochondrial biogenesis (Nisoli et al., 2003 and Nisoli et al., 2004) and SIRT1 expression (Nisoli et al., 2005).
Although CR has beneficial effects in humans (Heilbronn et al., 2006), such a dietary regimen is unlikely to be widely adopted in the elderly. As such, many researchers have focused on the development of CR mimetic compounds providing some of the benefits of dietary restriction without reduction in caloric intake (Ingram et al., 2004). Such attempts have been only partially successful in experimental models up to now and are not imminently feasible for humans.
Recent intriguing results indicate that amino acids leucine, isoleucine, and valine extend chronological life span in Saccharomyces cerevisiae ( Alvers et al., 2009), thus identifying branched-chain amino acids (BCAAs) as potential candidates in promoting survival. We investigated whether long-term dietary supplementation with a specific BCAA-enriched mixture (BCAAem) that improves age-related disorders in animals and humans ( Pansarasa et al., 2008 and Solerte et al., 2008a) also promotes mice survival. Here, we demonstrated that the BCAAem supplementation increased average life span of male mice, and this was accompanied by increased mitochondrial biogenesis and SIRT1 expression both in cardiac and skeletal muscles, unlike adipose tissues and liver of middle-aged mice. Further, the muscle ROS defense system genes were upregulated by BCAAem supplementation, resulting in decreased indices of oxidative damage