Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle

被引：96

作者：

Bigot, Anne ^{[1
]}

Duddy, William J. ^{[1
]}

Ouandaogo, Zamalou G. ^{[1
]}

Negroni, Elisa ^{[1
]}

Mariot, Virginie ^{[1
]}

Ghimbovschi, Svetlana ^{[2
]}

Harmon, Brennan ^{[2
]}

Wielgosik, Aurore ^{[1
]}

Loiseau, Camille ^{[1
,3
]}

Devaney, Joe ^{[2
]}

Dumonceaux, Julie ^{[1
]}

Butler-Browne, Gillian ^{[1
]}

Mouly, Vincent ^{[1
]}

Duguez, Stephanie ^{[1
]}

机构：

[1] Univ Paris 06, Sorbonne Univ, GH Pitie Salpetriere, INSERM UMRS974,CNRS FRE3617,CRM, Paris 13, France

[2] Childrens Natl Med Ctr, Core Intellectual & Dev Disabil Res Ctr IDDRC, GPB, Washington, DC 20010 USA

[3] Univ Paris 06, Sorbonne Univ, INSERM, UMR S 1158,Neurophysiol Resp Expt & Clin, Paris 13, France

来源：

CELL REPORTS | 2015年 / 13卷 / 06期

关键词：

HUMAN SKELETAL-MUSCLE; LARGE GENE LISTS; SATELLITE CELLS; PROGENITOR CELLS; SELF-RENEWAL; REVERSIBLE QUIESCENCE; EPIGENETIC REGULATION; ADULT MYOGENESIS; HUMAN MYOBLASTS; NOTCH;

D O I：

10.1016/j.celrep.2015.09.067

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The molecular mechanisms by which aging affects stem cell number and function are poorly understood. Murine data have implicated cellular senescence in the loss of muscle stem cells with aging. Here, using human cells and by carrying out experiments within a strictly pre-senescent division count, we demonstrate an impaired capacity for stem cell self-renewal in elderly muscle. We link aging to an increased methylation of the SPRY1 gene, a known regulator of muscle stem cell quiescence. Replenishment of the reserve cell pool was modulated experimentally by demethylation or siRNA knockdown of SPRY1. We propose that suppression of SPRY1 by age-associated methylation in humans inhibits the replenishment of the muscle stem cell pool, contributing to a decreased regenerative response in old age. We further show that aging does not affect muscle stem cell senescence in humans.

引用

页码：1172 / 1182

页数：11

共 51 条

[31]

Numerical densities of myonuclei and satellite cells in muscle fiber types in the aging human thyroarytenoid muscle: An immunohistochemical and stereological study using confocal laser scanning microscopy [J].