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| Status |
Public on May 08, 2014 |
| Title |
Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
In this study, we investigated signaling pathways in Skeletal muscle precursors that are altered with aging and age-related deficits in muscle regenerative potential. We performed fluorescence activated cell sorting (FACS) to obtain highly purified skeletal muscle satellite cells from young, middle-aged and old mice.
Parabiosis experiments indicate that impaired regeneration in aged mice is reversible by exposure to a young circulation, suggesting that young blood contains humoral "rejuvenating" factors that can restore regenerative function. Here, we demonstrate that the circulating protein growth differentiation factor 11 (GDF11) is a rejuvenating factor for skeletal muscle. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. These data indicate that GDF11 systemically regulates muscle aging and may be therapeutically useful for reversing age-related skeletal muscle and stem cell dysfunction.
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| Overall design |
We used Affymetrix Mouse Genome array to identify global transcriptional changes associated with age in skeletal muscle precursors.
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| Contributor(s) |
Sinha M, Jang YC, Oh J, Khong D, Wu EY, Manohar R, Miller C, Regalado SG, Loffredo F, Pancoast JR, Hirshman MF, Lebowitz J, Shadrach JL, Cerletti M, Kim MJ, Serwold T, Goodyear LJ, Rosner B, Lee RT, Wagers AJ |
| Citation(s) |
24797481 |
| Submission date |
Sep 12, 2013 |
| Last update date |
Feb 11, 2019 |
| Contact name |
Amy J Wagers |
| E-mail(s) |
amy_wagers@harvard.edu
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| Phone |
+1-617-309-2590
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| Organization name |
Joslin diabetes center and Harvard University
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| Department |
Stem Cell and Regenerative Biology
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| Lab |
Stem Cell and Regenerative Biology
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| Street address |
One Joslin place
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| City |
Boston |
| State/province |
MA |
| ZIP/Postal code |
02215 |
| Country |
USA |
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| Platforms (1) |
| GPL1261 |
[Mouse430_2] Affymetrix Mouse Genome 430 2.0 Array |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA219090 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE50821_RAW.tar |
47.4 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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