Document Type
Journal Article
Publication Date
11-10-2015
Journal
Cell Reports
Volume
13
Issue
6
Inclusive Pages
1172-1182
DOI
10.1016/j.celrep.2015.09.067
Keywords
Aging--metabolism; Cell Self Renewal; DNA Methylation; Membrane Proteins--genetics; Myoblasts--metabolism; Phosphoproteins--genetics
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.
Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.
APA Citation
Bigot, A., Duddy, W., Ouandaogo, Z., Negroni, E., Mariot, V., Ghimbovschi, S., Harmon, B., Wielgosik, A., Loiseau, C., Devaney, J., Dumonceaux, J., Butler-Browne, G., Mouly, V., & Duguez, S. (2015). Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle.. Cell Reports, 13 (6). http://dx.doi.org/10.1016/j.celrep.2015.09.067
Peer Reviewed
1
Open Access
1
Included in
Cell Biology Commons, Genetics and Genomics Commons, Integrative Biology Commons, Systems Biology Commons
Comments
Reproduced with permission of Elsevier B.V. Cell Reports.