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

Anne Bigot; William Duddy; Zamalou G Ouandaogo; Elisa Negroni; Virginie Mariot; Svetlana Ghimbovschi; Brennan Harmon; Aurore Wielgosik; Camille Loiseau; Joe Devaney; Julie Dumonceaux; Gillian Butler-Browne; Vincent Mouly; Stephanie Duguez

doi:10.1016/j.celrep.2015.09.067

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

Anne Bigot, William Duddy, Zamalou G Ouandaogo, Elisa Negroni, Virginie Mariot, Svetlana Ghimbovschi, Brennan Harmon, Aurore Wielgosik, Camille Loiseau, Joe Devaney, Julie Dumonceaux, Gillian Butler-Browne, Vincent Mouly, Stephanie Duguez

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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.

Original language	English
Pages (from-to)	1172-82
Number of pages	11
Journal	Cell Reports
Volume	13
Issue number	6
Early online date	29 Oct 2015
DOIs	https://doi.org/10.1016/j.celrep.2015.09.067
Publication status	Published (in print/issue) - 10 Nov 2015

Keywords

aging
DNA methylation
human muscle stem cell
myoblast
quiescence
sprouty1

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.celrep.2015.09.067Licence: CC BY-NC-ND

Final published versionFinal published version, 3.07 MBLicence: CC BY-NC-ND

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Bigot, A., Duddy, W., Ouandaogo, Z. G., 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), 1172-82. https://doi.org/10.1016/j.celrep.2015.09.067

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

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 = "aging, DNA methylation, human muscle stem cell, myoblast, quiescence, sprouty1",

author = "Anne Bigot and William Duddy and Ouandaogo, {Zamalou G} and Elisa Negroni and Virginie Mariot and Svetlana Ghimbovschi and Brennan Harmon and Aurore Wielgosik and Camille Loiseau and Joe Devaney and Julie Dumonceaux and Gillian Butler-Browne and Vincent Mouly and Stephanie Duguez",

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month = nov,

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doi = "10.1016/j.celrep.2015.09.067",

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Bigot, A, Duddy, W, Ouandaogo, ZG, 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, vol. 13, no. 6, pp. 1172-82. https://doi.org/10.1016/j.celrep.2015.09.067

TY - JOUR

T1 - Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle

AU - Bigot, Anne

AU - Duddy, William

AU - Ouandaogo, Zamalou G

AU - Negroni, Elisa

AU - Mariot, Virginie

AU - Ghimbovschi, Svetlana

AU - Harmon, Brennan

AU - Wielgosik, Aurore

AU - Loiseau, Camille

AU - Devaney, Joe

AU - Dumonceaux, Julie

AU - Butler-Browne, Gillian

AU - Mouly, Vincent

AU - Duguez, Stephanie

PY - 2015/11/10

Y1 - 2015/11/10

N2 - 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.

AB - 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.

KW - aging

KW - DNA methylation

KW - human muscle stem cell

KW - myoblast

KW - quiescence

KW - sprouty1

UR - https://www.sciencedirect.com/science/article/pii/S2211124715011092

UR - https://pure.ulster.ac.uk/en/publications/age-associated-methylation-suppresses-spry1-leading-to-a-failure--5

U2 - 10.1016/j.celrep.2015.09.067

DO - 10.1016/j.celrep.2015.09.067

M3 - Article

SN - 2211-1247

VL - 13

SP - 1172

EP - 1182

JO - Cell Reports

JF - Cell Reports

IS - 6

ER -

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

Abstract

Keywords

UN SDGs

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