Restoring Systemic GDF11 Levels Reverses Age-Related Dysfunction in Mouse Skeletal Muscle

被引：664

作者：

Sinha, Manisha ^{[1
,2
,3
,4
,5
]}

Jang, Young C. ^{[1
,2
,3
,5
]}

Oh, Juhyun ^{[1
,2
,3
,5
]}

Khong, Danika ^{[1
,2
,3
,5
]}

Wu, Elizabeth Y. ^{[1
,2
,3
,5
]}

Manohar, Rohan ^{[1
,2
,3
,5
]}

Miller, Christine ^{[1
,2
,3
,5
]}

Regalado, Samuel G. ^{[1
,2
,6
]}

Loffredo, Francesco S. ^{[1
,2
,7
,8
]}

Pancoast, James R. ^{[1
,2
,7
,8
]}

Hirshman, Michael F. ^{[3
]}

Lebowitz, Jessica ^{[1
,2
,3
,5
]}

Shadrach, Jennifer L. ^{[1
,2
,3
,4
]}

Cerletti, Massimiliano ^{[1
,2
,3
]}

Kim, Mi-Jeong ^{[3
]}

Serwold, Thomas ^{[3
]}

Goodyear, Laurie J. ^{[3
,9
,10
]}

Rosner, Bernard ^{[11
]}

Lee, Richard T. ^{[1
,2
]}

Wagers, Amy J. ^{[1
,2
,3
,4
,5
]}

机构：

[1] Harvard Univ, Harvard Stem Cell Inst, Cambridge, MA 02138 USA

[2] Harvard Univ, Dept Stem Cell & Regenerat Biol, Cambridge, MA 02138 USA

[3] Joslin Diabet Ctr, Boston, MA 02215 USA

[4] Howard Hughes Med Inst, Cambridge, MA USA

[5] Harvard Univ, Sch Med, Paul F Glenn Labs Biol Mech Aging, Boston, MA USA

[6] Univ Calif Berkeley, Berkeley, CA 94720 USA

[7] Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA

[8] Brigham Regenerat Med Ctr, Boston, MA USA

[9] Brigham & Womens Hosp, Dept Med, Boston, MA 02115 USA

[10] Harvard Univ, Sch Med, Boston, MA USA

[11] Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA

来源：

SCIENCE | 2014年 / 344卷 / 6184期

关键词：

DIFFERENTIATION FACTOR 11; DNA-DAMAGE; STEM-CELLS; MYOSTATIN; REJUVENATION; HYPERTROPHY; REPAIR;

D O I：

10.1126/science.1251152

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页码：649 / 652

页数：4

共 23 条

[1] Muscle hypertrophy driven by myostatin blockade does not require stem/precursor-cell activity [J].