title: Rapamycin increases oxidative stress response gene expression in adult stem cells.
abstract: Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescencein vitro and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age. To test our hypothesis, we exposed mice to rapamycin and then examined the transcriptome of their spermatogonial stem cells (SSCs). Gene expression microarray analysis revealed that numerous oxidative stress response genes were upregulated upon rapamycin treatment, including superoxide dismutase 1, glutathione reductase, and delta-aminolevulinate dehydratase. When we examined the expression of these genes in 55-week-old wild type SSCs, their levels were significantly reduced compared to 3-week-old SSCs, suggesting that their downregulation is coincident with the aging process in adult stem cells. We conclude that rapamycin-induced stimulation of oxidative stress response genes may promote cellular longevity in SSCs, while a decline in gene expression in aged stem cells could reflect the SSCs' diminished potential to alleviate oxidative stress, a hallmark of aging.
authors.affiliation: Human Molecular Genetics Program, Children's Memorial Research Center, Chicago, IL 60614, USA.
authors.forename: Amber E
authors.initials: AE
authors.lastname: Kofman
authors.forename: Margeaux R
authors.initials: MR
authors.lastname: McGraw
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Payne
mesh_terms: D000375:Aging / Q000235:genetics / Q000502:physiology; D000818:Animals; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects*; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology*; D013093:Spermatogonia / Q000187:drug effects* / Q000378:metabolism; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000235:genetics*; D013737:Testis / Q000187:drug effects / Q000254:growth & development; D059467:Transcriptome / Q000187:drug effects*
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus