Autophagy maintains stemness by preventing senescence

被引：1201

作者：

Garcia-Prat, Laura ^{[1
]}

Martinez-Vicente, Marta ^{[2
]}

Perdiguero, Eusebio ^{[1
]}

Ortet, Laura ^{[1
]}

Rodriguez-Ubreva, Javier ^{[3
]}

Rebollo, Elena ^{[4
]}

Ruiz-Bonilla, Vanessa ^{[1
]}

Gutarra, Susana ^{[1
]}

Ballestar, Esteban ^{[3
]}

Serrano, Antonio L. ^{[1
]}

Sandri, Marco ^{[5
,6
]}

Munoz-Canoves, Pura ^{[1
,7
]}

机构：

[1] Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain

[2] Vall dHebron Res Inst, Neurodegenerat Dis Res Grp, CIBERNED, E-08035 Barcelona, Spain

[3] Bellvitge Biomed Res Inst IDIBELL, Chromatin & Dis Grp, Canc Epigenet & Biol Programme PEBC, E-08907 Lhospitalet De Llobregat, Spain

[4] CSIC, Adv Fluorescence Microscopy Unit, Mol Biol Inst Barcelona IBMB, E-08028 Barcelona, Spain

[5] Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy

[6] Telethon Inst Genet & Med TIGEM, I-80131 Naples, Italy

[7] ICREA, E-08908 Barcelona, Spain

来源：

NATURE | 2016年 / 529卷 / 7584期

基金：

欧盟第七框架计划;

关键词：

SKELETAL-MUSCLE; MUSCULAR-DYSTROPHY; SATELLITE CELLS; LIFE-SPAN; P38; MAPK; QUIESCENT; PATHWAYS; SUPPORTS; NICHE; ROS;

D O I：

10.1038/nature16187

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：

070301 [无机化学]; 070403 [天体物理学]; 070507 [自然资源与国土空间规划学]; 090105 [作物生产系统与生态工程];

摘要：

During ageing, muscle stem-cell regenerative function declines. At advanced geriatric age, this decline is maximal owing to transition from a normal quiescence into an irreversible senescence state. How satellite cells maintain quiescence and avoid senescence until advanced age remains unknown. Here we report that basal autophagy is essential to maintain the stem-cell quiescent state in mice. Failure of autophagy in physiologically aged satellite cells or genetic impairment of autophagy in young cells causes entry into senescence by loss of proteostasis, increased mitochondrial dysfunction and oxidative stress, resulting in a decline in the function and number of satellite cells. Re-establishment of autophagy reverses senescence and restores regenerative functions in geriatric satellite cells. As autophagy also declines in human geriatric satellite cells, our findings reveal autophagy to be a decisive stem-cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.

引用

页码：37 / +

页数：21

共 54 条

[1]

p38 MAPK signaling underlies a cell-autonomous loss of stem cell self-renewal in skeletal muscle of aged mice [J].