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

    Research output: Contribution to journalArticle

    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.
    LanguageEnglish
    Pages1172-82
    JournalCell Reports
    Volume13
    Issue number6
    Early online date29 Oct 2015
    DOIs
    Publication statusPublished - 10 Nov 2015

    Fingerprint

    Methylation
    Stem cells
    Muscle
    Stem Cells
    Muscle Cells
    Cell Aging
    Muscles
    Aging of materials
    Small Interfering RNA
    Cell Count
    Genes
    Cells
    Experiments

    Keywords

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

    Cite this

    Bigot, Anne ; Duddy, William ; Ouandaogo, Zamalou G ; Negroni, Elisa ; Mariot, Virginie ; Ghimbovschi, Svetlana ; Harmon, Brennan ; Wielgosik, Aurore ; Loiseau, Camille ; Devaney, Joe ; Dumonceaux, Julie ; Butler-Browne, Gillian ; Mouly, Vincent ; Duguez, Stephanie. / Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle. In: Cell Reports. 2015 ; Vol. 13, No. 6. pp. 1172-82.
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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.",
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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

    Age-Associated Methylation Suppresses SPRY1, Leading to a Failure of Re-quiescence and Loss of the Reserve Stem Cell Pool in Elderly Muscle. / Bigot, Anne; Duddy, William; Ouandaogo, Zamalou G; Negroni, Elisa; Mariot, Virginie; Ghimbovschi, Svetlana; Harmon, Brennan; Wielgosik, Aurore; Loiseau, Camille; Devaney, Joe; Dumonceaux, Julie; Butler-Browne, Gillian; Mouly, Vincent; Duguez, Stephanie.

    In: Cell Reports, Vol. 13, No. 6, 10.11.2015, p. 1172-82.

    Research output: Contribution to journalArticle

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    AU - Duddy, William

    AU - Ouandaogo, Zamalou G

    AU - Negroni, Elisa

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    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

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    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.

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