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Cell Rep. 2015 Nov 10;13(6):1172-1182. doi: 10.1016/j.celrep.2015.09.067. Epub 2015 Oct 29.

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

Author information

1
Sorbonne Universités, UPMC University of Paris 06, INSERM UMRS974, CNRS FRE3617, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, Paris 13, France.
2
Genomics, Proteomics, and Bioinformatics (GPB) Core of the Intellectual and Developmental Disabilities Research Center (IDDRC), Children's National Medical Center, Washington, DC 20010, USA.
3
Sorbonne Universités, UPMC University of Paris 06, INSERM UMRS974, CNRS FRE3617, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, Paris 13, France; Sorbonne Universités, UPMC University of Paris 06, INSERM, UMR-S 1158, Neurophysiologie Respiratoire Expérimentale et Clinique, Paris 13, France.
4
Sorbonne Universités, UPMC University of Paris 06, INSERM UMRS974, CNRS FRE3617, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, Paris 13, France. Electronic address: vincent.mouly@upmc.fr.
5
Sorbonne Universités, UPMC University of Paris 06, INSERM UMRS974, CNRS FRE3617, Centre de Recherche en Myologie (CRM), GH Pitié Salpêtrière, Paris 13, France. Electronic address: stephanie.duguez@upmc.fr.

Abstract

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.

KEYWORDS:

DNA methylation; aging; human muscle stem cell; myoblast; quiescence; sprouty1

PMID:
26526994
DOI:
10.1016/j.celrep.2015.09.067
[Indexed for MEDLINE]
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