GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration

被引：512

作者：

Egerman, Marc A. ^{[1
]}

Cadena, Samuel M. ^{[1
]}

Gilbert, Jason A. ^{[1
]}

Meyer, Angelika ^{[3
]}

Nelson, Hallie N. ^{[2
]}

Swalley, Susanne E. ^{[1
]}

Mallozzi, Carolyn ^{[1
]}

Jacobi, Carsten ^{[3
]}

Jennings, Lori L. ^{[1
]}

Clay, Ieuan ^{[3
]}

Laurent, Gaelle ^{[1
]}

Ma, Shenglin ^{[1
]}

Brachat, Sophie ^{[3
]}

Lach-Trifilieff, Estelle ^{[3
]}

Shavlakadze, Tea ^{[1
]}

Trendelenburg, Anne-Ulrike ^{[1
]}

Brack, Andrew S. ^{[2
]}

Glass, David J. ^{[1
]}

机构：

[1] Novartis Inst Biomed Res, Cambridge, MA 02139 USA

[2] Massachusetts Gen Hosp, Ctr Regenerat Med, Boston, MA 02114 USA

[3] Novartis Inst Biomed Res, CH-4056 Basel, Switzerland

来源：

CELL METABOLISM | 2015年 / 22卷 / 01期

关键词：

GROWTH/DIFFERENTIATION FACTOR 11; TRANSFORMING-GROWTH-FACTOR; MYOGENIC DIFFERENTIATION; MYOBLAST DIFFERENTIATION; SIGNALING PATHWAY; BETA SUPERFAMILY; MYOSTATIN; ACTIVIN; MASS; FOLLISTATIN;

D O I：

10.1016/j.cmet.2015.05.010

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

Age-related frailty may be due to decreased skeletal muscle regeneration. The role of TGF-beta molecules myostatin and GDF11 in regeneration is unclear. Recent studies showed an age-related decrease in GDF11 and that GDF11 treatment improves muscle regeneration, which were contrary to prior studies. We now show that these recent claims are not reproducible and the reagents previously used to detect GDF11 are not GDF11 specific. We develop a GDF11-specific immunoassay and show a trend toward increased GDF11 levels in sera of aged rats and humans. GDF11 mRNA increases in rat muscle with age. Mechanistically, GDF11 and myostatin both induce SMAD2/3 phosphorylation, inhibit myoblast differentiation, and regulate identical downstream signaling. GDF11 significantly inhibited muscle regeneration and decreased satellite cell expansion in mice. Given early data in humans showing a trend for an age-related increase, GDF11 could be a target for pharmacologic blockade to treat age-related sarcopenia.

引用

页码：164 / 174

页数：11

共 32 条

[1]

Growth factors controlling muscle development [J].

Bass, J ;

Oldham, J ;

Sharma, M ;

Kambadur, R .

DOMESTIC ANIMAL ENDOCRINOLOGY, 1999, 17 (2-3) :191-197

[2]

Alterations in the TGFβ signaling pathway in myogenic progenitors with age [J].

Beggs, ML ;

Nagarajan, R ;

Taylor-Jones, JM ;

Nolen, G ;

MacNicol, M ;

Peterson, CA .

AGING CELL, 2004, 3 (06) :353-361

[3]

Relative roles of TGF-β1 and Wnt in the systemic regulation and aging of satellite cell responses [J].

Carlson, Morgan E. ;

Conboy, Michael J. ;

Hsu, Michael ;

Barchas, Laurel ;

Jeong, Jaemin ;

Agrawal, Anshu ;

Mikels, Amanda J. ;

Agrawal, Smita ;

Schaffer, David V. ;

Conboy, Irina M. .

AGING CELL, 2009, 8 (06) :676-689

[4]

Signaling pathways controlling skeletal muscle mass [J].

Egerman, Marc A. ;

Glass, David J. .

CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2014, 49 (01) :59-68

[5]

Gdf11 is a negative regulator of chondrogenesis and myogenesis in the developing chick limb [J].

Gamer, LW ;

Cox, KA ;

Small, C ;

Rosen, V .

DEVELOPMENTAL BIOLOGY, 2001, 229 (02) :407-420

[6]

Aptamer-Based Multiplexed Proteomic Technology for Biomarker Discovery [J].

Gold, Larry ;

Ayers, Deborah ;

Bertino, Jennifer ;

Bock, Christopher ;

Bock, Ashley ;

Brody, Edward N. ;

Carter, Jeff ;

Dalby, Andrew B. ;

Eaton, Bruce E. ;

Fitzwater, Tim ;

Flather, Dylan ;

Forbes, Ashley ;

Foreman, Trudi ;

Fowler, Cate ;

Gawande, Bharat ;

Goss, Meredith ;

Gunn, Magda ;

Gupta, Shashi ;

Halladay, Dennis ;

Heil, Jim ;

Heilig, Joe ;

Hicke, Brian ;

Husar, Gregory ;

Janjic, Nebojsa ;

Jarvis, Thale ;

Jennings, Susan ;

Katilius, Evaldas ;

Keeney, Tracy R. ;

Kim, Nancy ;

Koch, Tad H. ;

Kraemer, Stephan ;

Kroiss, Luke ;

Le, Ngan ;

Levine, Daniel ;

Lindsey, Wes ;

Lollo, Bridget ;

Mayfield, Wes ;

Mehan, Mike ;

Mehler, Robert ;

Nelson, Sally K. ;

Nelson, Michele ;

Nieuwlandt, Dan ;

Nikrad, Malti ;

Ochsner, Urs ;

Ostroff, Rachel M. ;

Otis, Matt ;

Parker, Thomas ;

Pietrasiewicz, Steve ;

Resnicow, Daniel I. ;

Rohloff, John .

PLOS ONE, 2010, 5 (12)

[7]

The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum [J].

Hill, JJ ;

Davies, MV ;

Pearson, AA ;

Wang, JH ;

Hewick, RM ;

Wolfman, NM ;

Qiu, YC .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (43) :40735-40741

[8]

Genomic and Proteomic Profiling Reveals Reduced Mitochondrial Function and Disruption of the Neuromuscular Junction Driving Rat Sarcopenia [J].

Ibebunjo, Chikwendu ;

Chick, Joel M. ;

Kendall, Tracee ;

Eash, John K. ;

Li, Christine ;

Zhang, Yunyu ;

Vickers, Chad ;

Wu, Zhidan ;

Clarke, Brian A. ;

Shi, Jun ;

Cruz, Joseph ;

Fournier, Brigitte ;

Brachat, Sophie ;

Gutzwiller, Sabine ;

Ma, QiCheng ;

Markovits, Judit ;

Broome, Michelle ;

Steinkrauss, Michelle ;

Skuba, Elizabeth ;

Galarneau, Jean-Rene ;

Gygi, Steven P. ;

Glassa, David J. .

MOLECULAR AND CELLULAR BIOLOGY, 2013, 33 (02) :194-212

[9]

Myostatin expression in porcine tissues: tissue specificity and developmental and postnatal regulation [J].

Ji, SQ ;

Losinski, RL ;

Cornelius, SG ;

Frank, GR ;

Willis, GM ;

Gerrard, DE ;

Depreux, FFS ;

Spurlock, ME .

AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1998, 275 (04) :R1265-R1273

[10]

Mutations in myostatin (GDF8) in double-muscled Belgian blue and Piedmontese cattle [J].

Kambadur, R ;

Sharma, M ;

Smith, TPL ;

Bass, JJ .

GENOME RESEARCH, 1997, 7 (09) :910-916

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