GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.
GDF11 Increases with Age and Inhibits Skeletal Muscle Regeneration.
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DOI：
10.1016/j.cmet.2015.05.010
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发表时间：
2015-07-07
期刊：
影响因子：
29
通讯作者：
Glass DJ
中科院分区：
文献类型：
--
作者：
Egerman MA;Cadena SM;Gilbert JA;Meyer A;Nelson HN;Swalley SE;Mallozzi C;Jacobi C;Jennings LL;Clay I;Laurent G;Ma S;Brachat S;Lach-Trifilieff E;Shavlakadze T;Trendelenburg AU;Brack AS;Glass DJ
骨骼肌相关的虚弱可能是由于骨骼肌再生减少。TGF-β分子肌肉生长抑制素和GDF 11在再生中的作用尚不清楚。最近的研究表明，GDF 11与年龄相关的减少，GDF 11治疗可改善肌肉再生，这与先前的研究相反。我们现在表明，这些最近的声明是不可重现的，以前用于检测GDF 11的试剂不是GDF 11特异性的。我们开发了一种GDF 11特异性免疫测定法，并显示出老年大鼠和人类血清中GDF 11水平升高的趋势。GDF 11 mRNA在大鼠肌肉中随年龄增长而增加。在机制上，GDF 11和肌肉生长抑制素都诱导SMAD 2/3磷酸化，抑制成肌细胞分化，并调节相同的下游信号传导。GDF 11显著抑制小鼠肌肉再生并减少卫星细胞扩增。鉴于人类的早期数据显示出年龄相关性增加的趋势，GDF 11可能是治疗年龄相关性肌肉减少症的药物阻断的靶点。
Age-related frailty may be due to decreased skeletal muscle regeneration. The role of TGF-β 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.
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影响因子：
3.7
作者：
Gold L;Ayers D;Bertino J;Bock C;Bock A;Brody EN;Carter J;Dalby AB;Eaton BE;Fitzwater T;Flather D;Forbes A;Foreman T;Fowler C;Gawande B;Goss M;Gunn M;Gupta S;Halladay D;Heil J;Heilig J;Hicke B;Husar G;Janjic N;Jarvis T;Jennings S;Katilius E;Keeney TR;Kim N;Koch TH;Kraemer S;Kroiss L;Le N;Levine D;Lindsey W;Lollo B;Mayfield W;Mehan M;Mehler R;Nelson SK;Nelson M;Nieuwlandt D;Nikrad M;Ochsner U;Ostroff RM;Otis M;Parker T;Pietrasiewicz S;Resnicow DI;Rohloff J;Sanders G;Sattin S;Schneider D;Singer B;Stanton M;Sterkel A;Stewart A;Stratford S;Vaught JD;Vrkljan M;Walker JJ;Watrobka M;Waugh S;Weiss A;Wilcox SK;Wolfson A;Wolk SK;Zhang C;Zichi D
通讯作者：
Zichi D
影响因子：
2.1
作者：
Bass, J;Oldham, J;Kambadur, R
通讯作者：
Kambadur, R
影响因子：
7.8
作者：
Beggs, ML;Nagarajan, R;Peterson, CA
通讯作者：
Peterson, CA
影响因子：
4.8
作者：
Hill, JJ;Davies, MV;Qiu, YC
通讯作者：
Qiu, YC
影响因子：
2.7
作者：
Gamer, LW;Cox, KA;Rosen, V
通讯作者：
Rosen, V