Multiple Pathways to the Same End: Mechanisms of Myonuclear Apoptosis in Sarcopenia of Aging

Marzetti, Emanuele; Privitera, Giuseppe; Simili, Vincenzo; Wohlgemuth, Stephanie E.; Aulisa, Lorenzo; Pahor, Marco; Leeuwenburgh, Christiaan

doi:10.1100/tsw.2010.27

Cited by 63 publications

(58 citation statements)

References 82 publications

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“…However, the characteristics of sarcopenia are type II muscle fiber-specific 15,16) , and a reduction of muscular capillary density in the elderly is only observed around type II muscle fibers 8,9) . Moreover, myonuclear apoptosis had been thought to be the root cause of sarcopenia 82) ; even though the fact remains that 70-80% of apoptosis in aged skeletal muscle occurs in capillary endothelial cells 11) . A decrease in vascular endothelial growth factor (VEGF) production by elderly skeletal muscle may be an underlying mechanism 9) .…”

Section: Effect Of Blood Flow Volume On Skeletal Muscle Protein Metabmentioning

confidence: 99%

Link between blood flow and muscle protein metabolism in elderly adults

Zempo

Isobe

Naito

2017

JPFSM

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The mechanism which causes sarcopenia, a loss of muscle mass and strength with aging, remains unclear. Muscle mass is controlled by the net balance between protein synthesis and breakdown; however, net balance differences in the basal state do not contribute to sarcopenia. On the other hand, anabolic resistance, a reduction in muscle protein synthesis in response to protein intake, does seem to be involved in sarcopenia. Muscles which are subject to anabolic resistance do not show incremental blood flow volume during the fed-state. Because the vascular system transports amino acids and other nutrients that are essential for muscle protein synthesis, blood flow volume may be a regulator of anabolic resistance. There is some evidence of a link between blood flow and muscle protein metabolism. In addition, a combination of resistance training and amino acid supplementation promotes a positive net protein balance. Resistance training improves, and detraining reduces blood flow volume; therefore, blood flow volume may be involved as a background mechanism for sarcopenia. Moreover, previous studies have shown that sodium nitroprusside, a vasodilatory nitric oxide donor, enhances muscle protein synthesis. Conversely, angiotensin II, a major vasoconstrictive peptide, induces skeletal muscle protein breakdown. In this review, we discuss a possible role for blood flow in skeletal muscle protein metabolism in elderly adults. The regulation of blood flow may prove to be a beneficial treatment for sarcopenia.

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Section: Effect Of Blood Flow Volume On Skeletal Muscle Protein Metabmentioning

confidence: 99%

Link between blood flow and muscle protein metabolism in elderly adults

Zempo

Isobe

Naito

2017

JPFSM

View full text Add to dashboard Cite

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“…As a consequence of this, the rate of mitochondrial transition pore formation has been shown to increase following denervation (1). These denervation-induced responses contribute to a significant increase in caspase-3 cleavage (26, 35) and myonuclear DNA fragmentation (1,16,23,35). Despite this robust activation of apoptosis during disuse atrophy, it is well recognized that the increases in apoptosis are only able to…”

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confidence: 99%

Denervation-induced mitochondrial dysfunction and autophagy in skeletal muscle of apoptosis-deficient animals

O'Leary

Vainshtein

Carter

et al. 2012

American Journal of Physiology-Cell Physiology

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-Skeletal muscle undergoes remarkable adaptations in response to chronic decreases in contractile activity, such as a loss of muscle mass, decreases in both mitochondrial content and function, as well as the activation of apoptosis. Although these adaptations are well known, questions remain regarding the signaling pathways that mediated these changes. Autophagy is an organelle turnover pathway that could contribute to these adaptations. The purpose of this study was to determine whether denervation-induced muscle disuse would result in the activation of autophagy gene expression in both wild-type (WT) and Bax/Bak double knockout (DKO) animals, which display an attenuated apoptotic response. Denervation caused a reduction in muscle mass for WT and DKO animals; however, there was a 40% attenuation in muscle atrophy in DKO animals. Mitochondrial state 3 respiration was significantly reduced, and reactive oxygen species production was increased by two-to threefold in both WT and DKO animals. Apoptotic markers, including cytosolic AIF and DNA fragmentation, were elevated in WT, but not in DKO animals following denervation. Autophagy proteins including LC3II, ULK1, ATG7, p62, and Beclin1 were increased similarly following denervation for both WT and DKO. Interestingly, denervation markedly increased the localization of LC3II to subsarcolemmal mitochondria, and this was more pronounced in the DKO animals. Thus denervation-induced muscle disuse activates both apoptotic and autophagic signaling pathways in muscle, and autophagic protein expression does not exhibit a compensatory increase in the presence of attenuated apoptosis. However, the absence of Bax and Bak may represent a potential signal to trigger mitophagy in muscle.reactive oxygen species; muscle atrophy; mitochondria; mitophagy MACROAUTOPHAGY (henceforth referred to as autophagy) is a highly conserved lysosomal-dependent degradation pathway that coordinates and oversees the digestion of organelles, proteins, and intracellular pathogens (4, 34, 42). More than 30 AuTophaGy-related (ATG) regulatory genes products have been identified that are known to facilitate the engulfment of cytoplasmic material into double-membraned vesicles called autophagosomes (4, 42), and to assist in their degradation through fusion with lysosomes (10, 21). As a consequence, autophagy plays a prominent housekeeping role, which maintains homeostasis by selectively eliminating cellular debris. Moreover, although the activity of the autophagic pathway can be increased in response to stress stimuli, the importance of maintaining adequate levels of autophagy for cellular health and function is best demonstrated in several disease conditions, such as Parkinson's and Pompe's disease (27, 41), which are attributable, at least in part, to mutations in either ATG proteins or other autophagy-related genes.Currently there is great interest in determining the meaningful purposes that autophagy has in regulating cellular health, and in more fully understanding the factors that direct selective for...

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“…Therefore, mechanistic approaches designed to unravel the mysteries of sarcopenia must focus on the process of skeletal muscle remodeling, in addition to atrophy. A number of molecular and cellular candidates have been linked to sarcopenia and remodeling, including IGF-1 and its splice variant mechano-growth factor (MGF) (38), disrupted mechanotransduction (94), alterations in satellite cell signaling (39,98), mitochondrial dysfunction (53), oxidative stress (118), apoptosis (68), autophagy (126), insulin resistance (121), and dysregulation of the ubiquitin/proteosome pathway (5). Satellite cells as pluripotent nuclei may differentiate into adipocytes or fibroblasts, particularly with advancing age or disease (98).…”

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confidence: 99%