Geriatric muscle stem cells switch reversible quiescence into senescence

被引：763

作者：

Sousa-Victor, Pedro ^{[1
]}

Gutarra, Susana ^{[1
]}

Garcia-Prat, Laura ^{[1
]}

Rodriguez-Ubreva, Javier ^{[2
]}

Ortet, Laura ^{[1
]}

Ruiz-Bonilla, Vanessa ^{[1
]}

Jardi, Merce ^{[1
]}

Ballestar, Esteban ^{[2
]}

Gonzalez, Susana ^{[3
]}

Serrano, Antonio L. ^{[1
]}

Perdiguero, Eusebio ^{[1
]}

Munoz-Canoves, Pura ^{[1
,4
]}

机构：

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

[2] Bellvitge Biomed Res Inst, Canc Epigenet & Biol Programme, Chromatin & Dis Grp, E-08907 Barcelona, Spain

[3] Ctr Nacl Invest Cardiovasc, Stem Cell Aging Grp, E-28029 Madrid, Spain

[4] Inst Catalana Recerca & Estudis Avancats, E-08010 Barcelona, Spain

来源：

NATURE | 2014年 / 506卷 / 7488期

关键词：

DUCHENNE MUSCULAR-DYSTROPHY; SKELETAL-MUSCLE; CELLULAR SENESCENCE; SATELLITE CELLS; P16(INK4A); MECHANISMS; MYOGENESIS; SARCOPENIA; CHROMATIN; BMI-1;

D O I：

10.1038/nature13013

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：

Regeneration of skeletal muscle depends on a population of adult stem cells (satellite cells) that remain quiescent throughout life. Satellite cell regenerative functions decline with ageing. Here we report that geriatric satellite cells are incapable of maintaining their normal quiescent state in muscle homeostatic conditions, and that this irreversibly affects their intrinsic regenerative and self-renewal capacities. In geriatric mice, resting satellite cells lose reversible quiescence by switching to an irreversible pre-senescence state, caused by derepression of p16(INK4a) (also called Cdkn2a). On injury, these cells fail to activate and expand, undergoing accelerated entry into a full senescence state (geroconversion), even in a youthful environment. p16(INK4a) silencing in geriatric satellite cells restores quiescence and muscle regenerative functions. Our results demonstrate that maintenance of quiescence in adult life depends on the active repression of senescence pathways. As p16(INK4a) is dysregulated in human geriatric satellite cells, these findings provide the basis for stem-cell rejuvenation in sarcopenic muscles.

引用

页码：316 / +

页数：15

共 50 条

[1]

Polycomb Mediated Epigenetic Silencing and Replication Timing at the INK4a/ARF Locus during Senescence [J].