Nuclear domains during muscle atrophy: nuclei lost or paradigm lost?

Gundersen, Kristian; Bruusgaard, Jo C.

doi:10.1113/jphysiol.2008.154369

Cited by 117 publications

(136 citation statements)

References 70 publications

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“…In addition to the present detraining study, several studies on atrophy have now failed to demonstrate loss of nuclei or myonuclear apoptosis (22,60,61). Given the methodological limitations of results obtained with conventional histology (61), there is currently no compelling evidence that nuclei are ever lost from intact muscle fibers.…”

Section: Discussionmentioning

confidence: 88%

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.

248

277

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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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Section: Discussionmentioning

confidence: 88%

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.

248

277

View full text Add to dashboard Cite

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“…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).…”

Section: Introductionmentioning

confidence: 97%

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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“…Our study shows that despite the hypertrophy induced by mesterolone administration, no significant changes in the MD occurred because of the increased number of myonuclei in hypertrophied fibers of mesterolone-treated birds. However, others have reported that the MD is maintained under certain conditions only, and there is a loose association between sarcoplasmic volume and myonuclear number within muscle fibers (Gunderson and Bruusgaard, 2008). Both concepts may be valid depending on several factors, such as species, age, and the type and magnitude of stimulus applied to induce hypertrophy.…”

Section: Discussionmentioning

confidence: 99%

Influence of Mesterolone on Satellite Cell Distribution and Fiber Morphology within Maturing Chicken Pectoralis Muscle

Allouh

Aldirawi

2012

The Anatomical Record

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Mesterolone is a synthetic oral anabolic androgenic steroid used to treat hypogonadism. There are frequent reports of mesterolone abuse in human and equine sports to increase muscle mass and strength. However, limited information is available about how this drug exerts its effects on skeletal muscle. Satellite cells (SCs) are mononuclear myogenic stem cells that contribute to postnatal muscle growth and repair. As SC activation and subsequent differentiation to new myonuclei is a major event during muscle hypertrophy, this study investigated the influence of mesterolone on SC distribution within the pectoralis muscle of chickens. Specifically, this study tested the hypotheses that mesterolone induces avian skeletal muscle hypertrophy, and that mesterolone increases the number of SCs in avian skeletal muscle. Robust immunocytochemical techniques and morphometric analyses were used to calculate the numbers of SCs and myonuclei. Also, DNA concentration and Pax7 protein levels were measured to confirm immunocytochemical findings. Mesterolone significantly increased pectoralis mass and fiber size. All SC indices and number of myonuclei increased significantly by mesterolone administration. In addition, greater DNA concentration and Pax7 protein expression were found in mesterolone-treated birds. This study indicates that mesterolone can induce avian skeletal muscle hypertrophy and that this is correlated with increased number of SCs. We suggest that SCs are key cellular intermediaries for mesterolone-induced muscle hypertrophy. Anat Rec,

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Nuclear domains during muscle atrophy: nuclei lost or paradigm lost?

Cited by 117 publications

References 70 publications

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

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

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

Influence of Mesterolone on Satellite Cell Distribution and Fiber Morphology within Maturing Chicken Pectoralis Muscle

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