Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.
Restoring systemic GDF11 levels reverses age-related dysfunction in mouse skeletal muscle.
复制标题
DOI：
10.1126/science.1251152
复制
发表时间：
2014-05-09
期刊：
影响因子：
--
通讯作者：
Wagers AJ
中科院分区：
文献类型：
--
作者：
Sinha M;Jang YC;Oh J;Khong D;Wu EY;Manohar R;Miller C;Regalado SG;Loffredo FS;Pancoast JR;Hirshman MF;Lebowitz J;Shadrach JL;Cerletti M;Kim MJ;Serwold T;Goodyear LJ;Rosner B;Lee RT;Wagers AJ
联体共生实验表明，老年小鼠的再生受损是可逆的，暴露于年轻的循环，这表明年轻的血液含有体液“返老还童”的因素，可以恢复再生功能。在这里，我们证明了循环蛋白生长分化因子11（GDF11）是骨骼肌的再生因子。通过异时联体共生或重组蛋白的全身递送，补充通常随年龄下降的全身GDF11水平，逆转了老年肌肉干细胞（卫星细胞）中的功能障碍并恢复了基因组完整性。老年小鼠中GDF11水平的增加也改善了肌肉结构和功能特征，并增加了力量和耐力运动能力。这些数据表明，GDF11系统地调节肌肉衰老，并可能在治疗上用于逆转与年龄相关的骨骼肌和干细胞功能障碍。
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.
登录
查看更多内容
影响因子：
64.5
作者：
Sherwood, RI;Christensen, JL;Wagers, AJ
通讯作者：
Wagers, AJ
影响因子：
64.8
作者：
Conboy, IM;Conboy, MJ;Rando, TA
通讯作者：
Rando, TA
影响因子：
3.7
作者：
Shefer G;Rauner G;Yablonka-Reuveni Z;Benayahu D
通讯作者：
Benayahu D
影响因子：
64.8
作者：
Rossi, Derrick J.;Bryder, David;Weissman, Irving L.
通讯作者：
Weissman, Irving L.
影响因子：
56.9
作者：
Brack, Andrew S.;Conboy, Michael J.;Rando, Thomas A.
通讯作者：
Rando, Thomas A.