Читать книгу Sarcopenia - Группа авторов - Страница 36

Discovery metabolomic studies that compared pairs of individuals with low and high muscle quality matched by age, sex, and body size found that plasma levels of branched‐chain amino acids (BCAAs) were higher in individuals with low compared with high muscle quality, operationalized as the ratio between muscle mass and muscle strength [50]. Interestingly, opposite to what had been found in blood, level of BCAAs in the muscle of participants with low muscle quality were higher than that in those with high muscle quality. While the reason behind these findings is not clear, these results are consistent with the notion that the administration of BCAAs, such as leucine, in the diet may prevent age‐related decline of muscle strength, decrease muscle fatigue, and alleviate muscle soreness, although there is some indication that this effect could be blunted in older persons [51, 52]. The scarcity of BCAAs within myofibers has important consequences. In myofibers, BCAAs have been shown to stimulate the Pi3K/Akt/mTOR cell signaling pathway; in particular, the mTORC1 controls protein synthesis by activating S6 kinase 1 (S6K1) and inhibiting 4E‐binding protein 1 (4EBP1) [53]. Low BCAAs lead to reduced protein synthesis and over time protein damage accumulation and lower muscle mass. Low BCAA availability also directly impacts mitochondria through at least two main mechanisms. Deficient mTORC1 activation and reduced SIRT1 biological activity, secondary to low BCAA availability in myofibers, contribute to a deficit in mitochondrial metabolism by underexpression of PGC1α, a master regulator of mitochondrial biogenesis. In addition, BCAAs undergo transamination by branched‐chain aminotransferases (BCATs) to form branched‐chain alpha‐ketoacids (BCKAs), and oxidative decarboxylation by the mitochondrial branched‐chain alpha‐ketoacid dehydrogenase (BCKDH) complex. This last step is highly modulated by factors that affect energy availability and consumption, such as nutrition, exercise, and inflammation [54]. Ultimately, carbons that stem from the BCAA catabolism enter the tricarboxylic acid (TCA) cycle as either acetyl‐CoA or succinyl‐CoA, getting completely oxidized. In summary, impaired BCAA entry in skeletal myofibers appears to be associated with reduced muscle quality, impaired mitochondrial biogenesis, and decreased mitochondrial substrate delivery.