Enhanced Expression of Myogenic Regulatory Genes in Aging Skeletal Muscle

Musarò, Antonio; Angelis, Maria Gabriella Cusella De; Germani, Antonia; Ciccarelli, Carmela; Molinaro, Mario; Zani, Bianca M.

doi:10.1006/excr.1995.1372

Cited by 93 publications

(85 citation statements)

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“…In a number of these studies, MRF responses and/or muscle repair mechanisms were found to be limited by old age (34,(41)(42)(43)61). This may result from heightened basal levels of MRFs in the aging muscle (7,34,35,49) because MRF expression tends to increase as the degree of sarcopenia advances (17).…”

Section: Effects Of Age On Load-mediated Changes In Regenerative Markersmentioning

confidence: 99%

“…Basal levels of some MRFs are upregulated in aging, sarcopenic muscle (7,34,49) and, based on recent findings in rodents, the magnitude of upregulation appears to be directly linked to the degree of sarcopenia (17), suggesting that sarcopenic muscles remain in a state of failing compensatory effort in an attempt to stave off degeneration and atrophy. Resistance loading upregulates MRF mRNA and protein concentrations (34, 53), presumably facilitating growth/regeneration mechanisms.…”

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confidence: 98%

“…Expression of the "early" MRFs, myogenic factor (myf)-5 and myogenic differentiation factor D (MyoD), commit somatic cells to the myogenic lineage, whereas the "late" MRFs, myf-6 and myogenin, terminally differentiate proliferative myoblasts toward formation of multinucleated myotubes in developing muscle (58), or into nuclear donors to developed myofibers for repair/regeneration and growth. Myogenin and MyoD are also implicated in regulating MHC transitions (16,47,48).Basal levels of some MRFs are upregulated in aging, sarcopenic muscle (7,34,49) and, based on recent findings in rodents, the magnitude of upregulation appears to be directly linked to the degree of sarcopenia (17), suggesting that sarcopenic muscles remain in a state of failing compensatory effort in an attempt to stave off degeneration and atrophy. Resistance loading upregulates MRF mRNA and protein concentrations (34, 53), presumably facilitating growth/regeneration mechanisms.…”

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confidence: 99%

“…These events are regulated by several local processes that appear to respond in a load-dependent manner. Myogenic regulatory factors (MRFs) are basic helix-loop-helix transcription factors specific to skeletal muscle that regulate satellite cell differentiation and induce transcription of skeletal muscle-specific genes such as creatine kinase, myosin light chains, myosin heavy chains (MHC), troponin I, and desmin (10,44,49,53). Expression of the "early" MRFs, myogenic factor (myf)-5 and myogenic differentiation factor D (MyoD), commit somatic cells to the myogenic lineage, whereas the "late" MRFs, myf-6 and myogenin, terminally differentiate proliferative myoblasts toward formation of multinucleated myotubes in developing muscle (58), or into nuclear donors to developed myofibers for repair/regeneration and growth.…”

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Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults

Kosek

Kim

Petrella

et al. 2006

Journal of Applied Physiology

408

336

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. Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults. J Appl Physiol 101: [531][532][533][534][535][536][537][538][539][540][541][542][543][544] 2006. First published April 13, 2006; doi:10.1152/japplphysiol.01474.2005.-Resistance training (RT) has shown the most promise in reducing/reversing effects of sarcopenia, although the optimum regime specific for older adults remains unclear. We hypothesized myofiber hypertrophy resulting from frequent (3 days/wk, 16 wk) RT would be impaired in older (O; 60 -75 yr; 12 women, 13 men), sarcopenic adults compared with young (Y; 20 -35 yr; 11 women, 13 men) due to slowed repair/regeneration processes. Myofiber-type distribution and crosssectional area (CSA) were determined at 0 and 16 wk. Transcript and protein levels of myogenic regulatory factors (MRFs) were assessed as markers of regeneration at 0 and 24 h postexercise, and after 16 wk. Only Y increased type I CSA 18% (P Ͻ 0.001). O showed smaller type IIa (Ϫ16%) and type IIx (Ϫ24%) myofibers before training (P Ͻ 0.05), with differences most notable in women. Both age groups increased type IIa (O, 16%; Y, 25%) and mean type II (O, 23%; Y, 32%) size (P Ͻ 0.05). Growth was generally most favorable in young men. Percent change scores on fiber size revealed an age ϫ gender interaction for type I fibers (P Ͻ 0.05) as growth among Y (25%) exceeded that of O (4%) men. Myogenin and myogenic differentiation factor D (MyoD) mRNAs increased (P Ͻ 0.05) in Y and O, whereas myogenic factor (myf)-5 mRNA increased in Y only (P Ͻ 0.05). Myf-6 protein increased (P Ͻ 0.05) in both Y and O. The results generally support our hypothesis as 3 days/wk training led to more robust hypertrophy in Y vs. O, particularly among men. However, this differential hypertrophy adaptation was not explained by age variation in MRF expression. sarcopenia; myogenin; MyoD; myosin heavy chain IT IS WELL ESTABLISHED THAT muscle mass declines with age (termed sarcopenia). In the knee extensors (e.g., vastus lateralis), which are important for ambulation and weight-bearing function, a 30% decrease in whole muscle size occurs between the ages of 50 and 80 yr (15,40). This whole muscle atrophy results from atrophy of type II myofibers (34) and apparent loss of both type I and type II motor units as evidence from cadaveric studies of vastus lateralis indicate the number of myofibers, regardless of fiber type, declines substantially between the sixth and eighth decades (39). In the United States, $18.5 billion of total direct health care costs in 2000 were attributable to sarcopenia (31), and this will undoubtedly increase because the percentage of American adults 65 yr and older is expected to increase from one in nine to 20% of the adult population by 2030 (National Institute on Aging statistics). Resistance training has shown the most promise among interventions aimed to decrease the effects of sarcopenia, as it enhances strength, power, and mobility function and induces varying degrees of skeletal musc...

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Section: Effects Of Age On Load-mediated Changes In Regenerative Markersmentioning

confidence: 99%

mentioning

confidence: 98%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults

Kosek

Kim

Petrella

et al. 2006

Journal of Applied Physiology

408

336

View full text Add to dashboard Cite

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“…Myogenin is expressed prominently at the onset of myocyte differentiation as embryonic and fetal development proceed, with recruitment of new myoblasts to the differentiated state continuing throughout this period and into the early postnatal period (Sassoon et al 1989;Wright et al 1989;Hannon et al 1992). In healthy wildtype adult muscle, myogenin is down-regulated, as muscle matures, around the time of innervation, but it can be up-regulated later during muscle regeneration in response to diverse stimuli (e.g., Grounds et al 1992), during aging (Musarò et al 1995;Kostrominova et al 2000), and upon denervation (Eftimie et al 1991;Buonanno et al 1992). Knocking out myogenin perinatally leads to a generally normal skeletal muscle phenotype, but with reduced body size (Knapp et al 2006).…”

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confidence: 99%

A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle

Berghella¹,

Angelis²,

Buysscher³

et al. 2008

Genes Dev.

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Myogenin is the dominant transcriptional regulator of embryonic and fetal muscle differentiation and during maturation is profoundly down-regulated. We show that a highly conserved 17-bp DNA cis-acting sequence element located upstream of the myogenin promoter (myogHCE) is essential for postnatal repression of myogenin in transgenic animals. We present multiple lines of evidence supporting the idea that repression is mediated by the Y-box protein MSY-3. Electroporation in vivo shows that myogHCE and MSY-3 are required for postnatal repression. We further show that, in the C2C12 cell culture system, ectopic MSY-3 can repress differentiation, while reduced MSY-3 promotes premature differentiation. MSY-3 binds myogHCE simultaneously with the homeodomain protein Pbx in postnatal innervated muscle. We therefore propose a model in which the myogHCE motif operates as a switch by specifying opposing functions; one that was shown previously is regulated by MyoD and Pbx and it specifies a chromatin opening, gene-activating function at the time myoblasts begin to differentiate; the other includes MYS-3 and Pbx, and it specifies a repression function that operates during and after postnatal muscle maturation in vivo and in myoblasts before they begin to differentiate.[Keywords: CsdA; MSY-3; myogenin; Y-box; innervation; muscle maturation] Supplemental material is available at http://www.genesdev.org.

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MRF4 can substitute for myogenin during early stages of myogenesis

Zhu

Miller

1997

Dev. Dyn.

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Enhanced Expression of Myogenic Regulatory Genes in Aging Skeletal Muscle

Cited by 93 publications

References 0 publications

Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults

Efficacy of 3 days/wk resistance training on myofiber hypertrophy and myogenic mechanisms in young vs. older adults

A highly conserved molecular switch binds MSY-3 to regulate myogenin repression in postnatal muscle

MRF4 can substitute for myogenin during early stages of myogenesis

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