Molecular analyses provide insight into mechanisms underlying sarcopenia and myofibre denervation in old skeletal muscles of mice

Barns, Mitchell; Gondro, Cedric; Tellam, Ross L.; Radley‐Crabb, Hannah G.; Grounds, Miranda D.; Shavlakadze, Tea

doi:10.1016/j.biocel.2014.04.025

Cited by 72 publications

(103 citation statements)

References 79 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similar to our earlier report for female C57BL/6J mice (Barns et al 2014), the present study found that AKT(Ser473) phosphorylation was not altered in quadriceps muscles of freely fed C57BL/6J males aged between 4 and 24 m.…”

Section: Discussionsupporting

confidence: 92%

“…We have previously shown increased rpS6 phosphorylation in sarcopenic quadriceps muscles of freely fed female C57BL/6J mice aged 24 -29 m (Barns et al 2014), which was suggestive of increased mTORC1 signaling.…”

Section: Discussionmentioning

confidence: 94%

“…MuRF1 is a muscle-specific ubiquitin ligase that facilitates degradation of thick contractile filaments during muscle atrophy (Clarke et al 2007;Cohen et al 2009). Reports on the regulation of MuRF1 in old skeletal muscle are inconsistent and may be due to the sampling of limited ages (usually one young and one old group) (Clavel et al 2006;Altun et al 2010;Gaugler et al 2011) or use of different muscle types, gender and species (Clavel et al 2006;Edstrom et al 2006;Barns et al 2014). In addition, most studies measure MuRF1 transcript but not protein levels (reviewed in (Demontis et al 2013)).…”

Section: Proteasomal Degradation: Murf1 and Fbxo32mentioning

confidence: 99%

“…2A,B). MuRF1 protein was quantified in the 1% NP40 detergent insoluble fraction, which is enriched with muscle contractile proteins (Clarke et al 2007;Shavlakadze et al 2013b;Barns et al 2014), as MuRF1 facilitates myosin degradation (Clarke et al 2007). MuRF1 protein levels in the 1% NP40 insoluble fraction decreased between 4 and 18 m by 56%, and further increased between 18 and 24 m returning to a level similar to 4 m (Fig.…”

Section: Protein Degradation Pathways In Freely Fed Micementioning

confidence: 99%

See 3 more Smart Citations

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

White

McMahon

et al. 2016

The International Journal of Biochemistry & Cell Biology

Self Cite

View full text Add to dashboard Cite

Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 94%

Section: Proteasomal Degradation: Murf1 and Fbxo32mentioning

confidence: 99%

Section: Protein Degradation Pathways In Freely Fed Micementioning

confidence: 99%

See 2 more Smart Citations

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

White

McMahon

et al. 2016

The International Journal of Biochemistry & Cell Biology

Self Cite

View full text Add to dashboard Cite

“…In this context, complete denervation is rare in NMJs from aged normal STN; however, partial denervation, terminal sprouts, and aneural AChRs were detected (39,40). Changes in Chrng in aged normal STN have not been studied; however, increases in expression of Chrng and other denervation markers were reported to occur in aged normal quadriceps (69) and seemed unaccompanied by motoneuron loss (70).…”

Section: Figmentioning

confidence: 99%

Muscle-Derived Extracellular Signal-Regulated Kinases 1 and 2 Are Required for the Maintenance of Adult Myofibers and Their Neuromuscular Junctions

Seaberg

Henslee

Wang

et al. 2015

Molecular and Cellular Biology

View full text Add to dashboard Cite

The Ras-extracellular signal-regulated kinase 1 and 2 (ERK1/2) pathway appears to be important for the development, maintenance, aging, and pathology of mammalian skeletal muscle. Yet no gene targeting of Erk1/2 in muscle fibers in vivo has been reported to date. We combined a germ line Erk1 mutation with Cre-loxP Erk2 inactivation in skeletal muscle to produce, for the first time, mice lacking ERK1/2 selectively in skeletal myofibers. Animals lacking muscle ERK1/2 displayed stunted postnatal growth, muscle weakness, and a shorter life span. Their muscles examined in this study, sternomastoid and tibialis anterior, displayed fragmented neuromuscular synapses and a mixture of modest fiber atrophy and loss but failed to show major changes in fiber type composition or absence of cell surface dystrophin. Whereas the lack of only ERK1 had no effects on the phenotypes studied, the lack of myofiber ERK2 explained synaptic fragmentation in the sternomastoid but not the tibialis anterior and a decrease in the expression of the acetylcholine receptor (AChR) epsilon subunit gene mRNA in both muscles. A reduction in AChR protein was documented in line with the above mRNA results. Evidence of partial denervation was found in the sternomastoid but not the tibialis anterior. Thus, myofiber ERK1/2 are differentially required for the maintenance of myofibers and neuromuscular synapses in adult mice. Mitogen-activated protein kinases (MAPKs) are components of intracellular signaling modules that control a myriad of cellular processes. MAPK modules consist of 3 core protein kinase components. The most downstream is the actual MAPK, an S/T kinase that phosphorylates the transcription factors, cytoskeletal elements, or other kinases that are the targets of regulation by signaling cascades started at the cell surface. A MAPK is activated by an upstream MAPK kinase (MAP2K), which, in turn, is activated by a MAP2K kinase (MAP3K). MAP3Ks are usually at the receiving end of signals derived from small, monomeric GTPases such as the Ras family or by other more intricate mechanisms (1). In mammalian cells, the prototypical MAPK module is composed of the MAPKs extracellular signal-regulated kinases 1 and 2 (ERK1/2), the MAP2Ks MEK1/2, and the MAP3K Raf. ERK1/2 regulate normal cellular responses to multiple growth factors and cytokines in proliferation, differentiation, and apoptosis (2, 3).Multiple studies suggest an important role for the Ras-ERK1/2 pathway in the development, normal maintenance, aging, and pathology of mammalian skeletal muscle. Thus, ERK1/2 activity has both stimulatory and inhibitory roles in the differentiation of cultured skeletal myotubes that vary with the stage of this protracted process (4-8). ERK1/2 have been implicated in the maintenance of adult skeletal muscle mass (9) and, seemingly paradoxically, in the control of both the fast-twitch (10) and the slow-twitch (11) fiber type phenotypes. Alterations in levels of ERK1/2 activity in aging rodent muscle correlate with sarcopenia (12), the loss of muscle mass and ...

show abstract

A Lifecourse Approach to Sarcopenia

Dodds

Sayer

2021

Sarcopenia

View full text Add to dashboard Cite

Molecular analyses provide insight into mechanisms underlying sarcopenia and myofibre denervation in old skeletal muscles of mice

Cited by 72 publications

References 79 publications

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

High mTORC1 signaling is maintained, while protein degradation pathways are perturbed in old murine skeletal muscles in the fasted state

Muscle-Derived Extracellular Signal-Regulated Kinases 1 and 2 Are Required for the Maintenance of Adult Myofibers and Their Neuromuscular Junctions

A Lifecourse Approach to Sarcopenia

Contact Info

Product

Resources

About