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

Anne Bigot | Zendy; William Duddy | Zendy; Zamalou Gisèle Ouandaogo | Zendy; Elisa Négroni | Zendy; Virginie Mariot | Zendy; Svetlana Ghimbovschi | Zendy; Brennan Harmon | Zendy; Aurore Wielgosik | Zendy; Camille Loiseau | Zendy; Joe Devaney | Zendy; Julie Dumonceaux | Zendy; Gillian ButlerBrowne | Zendy; Vincent Mouly | Zendy; Stéphanie Duguez | Zendy

Open Access

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

Author(s) -

Anne Bigot,

William Duddy,

Zamalou Gisèle Ouandaogo,

Elisa Négroni,

Virginie Mariot,

Svetlana Ghimbovschi,

Brennan Harmon,

Aurore Wielgosik,

Camille Loiseau,

Joe Devaney,

Julie Dumonceaux,

Gillian ButlerBrowne,

Vincent Mouly,

Stéphanie Duguez

Publication year - 2015

Publication title -

cell reports

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.264

H-Index - 154

eISSN - 2639-1856

pISSN - 2211-1247

DOI - 10.1016/j.celrep.2015.09.067

Subject(s) - stem cell , senescence , microbiology and biotechnology , biology , dna methylation , regulator , stem cell theory of aging , myocyte , methylation , cell division , skeletal muscle , cell , genetics , endocrinology , gene expression , progenitor cell , gene , stem cell factor

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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