Premature aging in skeletal muscle lacking serum response factor.
Aging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Fact...
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doaj-3aafa779956c4611ac705167a707de192020-11-25T01:11:57ZengPublic Library of Science (PLoS)PLoS ONE1932-62032008-01-01312e391010.1371/journal.pone.0003910Premature aging in skeletal muscle lacking serum response factor.Charlotte LahouteAthanassia SotiropoulosMarilyne FavierIsabelle Guillet-DeniauClaude CharvetArnaud FerryGillian Butler-BrowneDaniel MetzgerDavid TuilDominique DaegelenAging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Factor) is a crucial transcription factor for muscle-specific gene expression and for post-natal skeletal muscle growth. To assess its role in adult skeletal muscle physiology, we developed a post-mitotic myofiber-specific and tamoxifen-inducible SRF knockout model. Five months after SRF loss, no obvious muscle phenotype was observed suggesting that SRF is not crucial for myofiber maintenance. However, mutant mice progressively developed IIB myofiber-specific atrophy accompanied by a metabolic switch towards a more oxidative phenotype, muscular lipid accumulation, sarcomere disorganization and fibrosis. After injury, mutant muscles exhibited an altered regeneration process, showing smaller regenerated fibers and persistent fibrosis. All of these features are strongly reminiscent of abnormalities encountered in aging skeletal muscle. Interestingly, we also observed an important age associated decrease in SRF expression in mice and human muscles. Altogether, these results suggest that a naturally occurring SRF down-regulation precedes and contributes to the muscle aging process. Indeed, triggering SRF loss in the muscles of mutant mice results in an accelerated aging process.http://europepmc.org/articles/PMC2593784?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Charlotte Lahoute Athanassia Sotiropoulos Marilyne Favier Isabelle Guillet-Deniau Claude Charvet Arnaud Ferry Gillian Butler-Browne Daniel Metzger David Tuil Dominique Daegelen |
spellingShingle |
Charlotte Lahoute Athanassia Sotiropoulos Marilyne Favier Isabelle Guillet-Deniau Claude Charvet Arnaud Ferry Gillian Butler-Browne Daniel Metzger David Tuil Dominique Daegelen Premature aging in skeletal muscle lacking serum response factor. PLoS ONE |
author_facet |
Charlotte Lahoute Athanassia Sotiropoulos Marilyne Favier Isabelle Guillet-Deniau Claude Charvet Arnaud Ferry Gillian Butler-Browne Daniel Metzger David Tuil Dominique Daegelen |
author_sort |
Charlotte Lahoute |
title |
Premature aging in skeletal muscle lacking serum response factor. |
title_short |
Premature aging in skeletal muscle lacking serum response factor. |
title_full |
Premature aging in skeletal muscle lacking serum response factor. |
title_fullStr |
Premature aging in skeletal muscle lacking serum response factor. |
title_full_unstemmed |
Premature aging in skeletal muscle lacking serum response factor. |
title_sort |
premature aging in skeletal muscle lacking serum response factor. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2008-01-01 |
description |
Aging is associated with a progressive loss of muscle mass, increased adiposity and fibrosis that leads to sarcopenia. At the molecular level, muscle aging is known to alter the expression of a variety of genes but very little is known about the molecular effectors involved. SRF (Serum Response Factor) is a crucial transcription factor for muscle-specific gene expression and for post-natal skeletal muscle growth. To assess its role in adult skeletal muscle physiology, we developed a post-mitotic myofiber-specific and tamoxifen-inducible SRF knockout model. Five months after SRF loss, no obvious muscle phenotype was observed suggesting that SRF is not crucial for myofiber maintenance. However, mutant mice progressively developed IIB myofiber-specific atrophy accompanied by a metabolic switch towards a more oxidative phenotype, muscular lipid accumulation, sarcomere disorganization and fibrosis. After injury, mutant muscles exhibited an altered regeneration process, showing smaller regenerated fibers and persistent fibrosis. All of these features are strongly reminiscent of abnormalities encountered in aging skeletal muscle. Interestingly, we also observed an important age associated decrease in SRF expression in mice and human muscles. Altogether, these results suggest that a naturally occurring SRF down-regulation precedes and contributes to the muscle aging process. Indeed, triggering SRF loss in the muscles of mutant mice results in an accelerated aging process. |
url |
http://europepmc.org/articles/PMC2593784?pdf=render |
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