Nuclear Apoptosis Contributes to Sarcopenia

Alway, Stephen E.; Siu, Parco M.

doi:10.1097/jes.0b013e318168e9dc

Cited by 118 publications

(96 citation statements)

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“…As each nucleus determines the transcription in its cytoplasmic neighbourhood (Pavlath et al, 1989), the myonuclear domain (MND) is defined as the volume unit in which the transcriptional activity is controlled by a single myonucleus. It is generally accepted that muscle hypertrophy is related to an increased myonuclear number through activation of satellite cells (Kadi et al, 2005;Mackey et al, 2007), while muscular atrophy is related to an apoptotic decrease in myonuclear number (Allen et al, 1997a,b;Alway & Siu, 2008). However, there are several reports demonstrating a less stringent relationship between myonuclear number and fibre size, i.e., there are reports of muscle fibre hypertrophy without satellite cell activation (McCarthy & Esser, 2007) as well as atrophy accompanied by either an increased, decreased or unaltered number of myonuclei (Allen et al, 1995(Allen et al, , 1996(Allen et al, , 1997aKasper & Xun, 1996;Gundersen & Bruusgaard, 2008).…”

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confidence: 99%

Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells

et al. 2010

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SummaryThe skeletal muscle fibre is a syncitium where each myonucleus regulates the gene products in a finite volume of the cytoplasm, i.e., the myonuclear domain (MND). We analysed aging-and gender-related effects on myonuclei organization and the MND size in single muscle fibres from six young (21-31 years) and nine old men (72-96 years), and from six young (24-32 years) and nine old women (65-96 years), using a novel image analysis algorithm applied to confocal images. Muscle fibres were classified according to myosin heavy chain (MyHC) isoform expression. Our image analysis algorithm was effective in determining the spatial organization of myonuclei and the distribution of individual MNDs along the single fibre segments. Significant linear relations were observed between MND size and fibre size, irrespective age, gender and MyHC isoform expression. The spatial organization of individual myonuclei, calculated as the distribution of nearest neighbour distances in 3D, and MND size were affected in old age, but changes were dependent on MyHC isoform expression. In type I muscle fibres, average NN-values were lower and showed an increased variability in old age, reflecting an aggregation of myonuclei in old age. Average MND size did not change in old age, but there was an increased MND size variability. In type IIa fibres, average NN-values and MND sizes were lower in old age, reflecting the smaller size of these muscle fibres in old age. It is suggested that these changes have a significant impact on protein synthesis and degradation during the aging process.

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Section: Introductionmentioning

confidence: 99%

Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells

et al. 2010

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“…Muscle cells can be five orders of magnitude larger than mononucleated cells, and muscle fibers are one of the very few multinuclear cell types in vertebrates (18). When the muscle fibers increase in size, it has been believed that nuclei are added by mitosis and subsequent fusion of muscle stem cells to the muscle fibers and that the "excess" myonuclei are removed by selective apoptosis of some of the nuclei during atrophy (20,21). Such mechanisms would serve to keep the cytoplasmic nuclear domain size constant.…”

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Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining

Bruusgaard

Johansen

Egner

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

261

283

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Effects of previous strength training can be long-lived, even after prolonged subsequent inactivity, and retraining is facilitated by a previous training episode. Traditionally, such "muscle memory" has been attributed to neural factors in the absence of any identified local memory mechanism in the muscle tissue. We have used in vivo imaging techniques to study live myonuclei belonging to distinct muscle fibers and observe that new myonuclei are added before any major increase in size during overload. The old and newly acquired nuclei are retained during severe atrophy caused by subsequent denervation lasting for a considerable period of the animal's lifespan. The myonuclei seem to be protected from the high apoptotic activity found in inactive muscle tissue. A hypertrophy episode leading to a lasting elevated number of myonuclei retarded disuse atrophy, and the nuclei could serve as a cell biological substrate for such memory. Because the ability to create myonuclei is impaired in the elderly, individuals may benefit from strength training at an early age, and because anabolic steroids facilitate more myonuclei, nuclear permanency may also have implications for exclusion periods after a doping offense. muscle memory | muscle nuclei | muscle atrophy | muscle hypertrophy | apoptosis

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“…Of particular interest in the current study was to determine whether redox-sensitive apoptotic signaling (52) could be suppressed by resveratrol administration during experimentally induced muscle disuse. This is an important area of inquiry, because myonuclei undergo apoptosis during muscle disuse (45,47), and this is thought to contribute to fiber atrophy, especially in aging muscles (5). Likewise, muscle disuse is associated with increases in oxidative stress (1,30), presumably mediated through mitochondrial dysfunction via ROS production and the regulation of the apoptotic pathway (2,20,47).…”

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“…Resveratrol (3,5,4,trihydroxystilbene) is a naturally occurring polyphenol found in more than 70 plant species, including grapes, peanuts, and mulberries (7). Resveratrol has gained popularity over the past decade due to its potent antioxidant and antiaging properties (27,39).…”

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Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats

Jackson

Ryan

Hao

2010

American Journal of Physiology-Regulatory, Integrative and Comp

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. Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats. Am J Physiol Regul Integr Comp Physiol 299: R1572-R1581, 2010. First published September 22, 2010 doi:10.1152/ajpregu.00489.2010.-Hindlimb suspension (HLS) elicits muscle atrophy, oxidative stress, and apoptosis in skeletal muscle. Increases in oxidative stress can have detrimental effects on muscle mass and function, and it can potentially lead to myonuclear apoptosis. Resveratrol is a naturally occurring polyphenol possessing both antioxidant and antiaging properties. To analyze the capacity of resveratrol to attenuate oxidative stress, apoptosis and muscle force loss were measured following 14 days of HLS. Young (6 mo) and old (34 mo) rats were administered either 12.5 mg·kg Ϫ1 ·day Ϫ1 of trans-resveratrol, or 0.1% carboxymethylcellulose for 21 days, including 14 days of HLS. HLS induced a significant decrease in plantarflexor isometric force, but resveratrol blunted this loss in old animals. Resveratrol increased gastrocnemius catalase activity, MnSOD activity, and MnSOD protein content following HLS. Resveratrol reduced hydrogen peroxide and lipid peroxidation levels in muscles from old animals after HLS. Caspase 9 abundance was reduced and Bcl-2 was increased, but other apoptotic markers were not affected by resveratrol in the gastrocnemius muscle after HLS. The data indicate that resveratrol has a protective effect against oxidative stress and muscle force loss in old HLS animals; however, resveratrol was unable to attenuate apoptosis following HLS. These results suggest that resveratrol has the potential to be an effective therapeutic agent to treat muscle functional decrements via improving the redox status associated with disuse. oxidative stress; apoptosis; hindlimb suspension; aging BOTH ADVANCED AGE AND SKELETAL muscle disuse are associated with atrophy and an increased production of reactive oxygen species (ROS) in skeletal muscle (30), leading to an augmented oxidant load. Oxidative stress occurs when an increase in oxidant production exceeds an organisms' capacity to buffer them, via a complex coordination of the endogenous antioxidant defense system. During extended periods of oxidative stress, there is an eventual loss of cellular integrity mitigated by the oxidation of lipids (32), proteins (29), and nucleic acids (21), promoting a cycle of increased oxidant production. This results in elevated levels of oxidative damage, which limits both the cellular repair system and the enzymatic antioxidant defense system (16). The exact mechanisms by which oxidative stress acts as a potentiator of muscle atrophy are largely unknown; however, several links between oxidative stress and atrophy have been postulated (35).Oxidative stress is upstream of apoptotic signaling in muscle cells in vitro (49), and results in the initiation of the intrinsic mitochondrial apoptotic pathway. Of particular interest in the current study was to determine whether...

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Nuclear Apoptosis Contributes to Sarcopenia

Cited by 118 publications

References 30 publications

Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells

Effects of aging and gender on the spatial organization of nuclei in single human skeletal muscle cells

Myonuclei acquired by overload exercise precede hypertrophy and are not lost on detraining

Mediation of endogenous antioxidant enzymes and apoptotic signaling by resveratrol following muscle disuse in the gastrocnemius muscles of young and old rats

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