mTOR signaling plays a critical role in the defects observed in muscle-derived stem/progenitor cells isolated from a murine model of accelerated aging.
mTOR signaling plays a critical role in the defects observed in muscle-derived stem/progenitor cells isolated from a murine model of accelerated aging.
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DOI：
10.1002/jor.23409
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发表时间：
2017-07
期刊：
影响因子：
--
通讯作者：
Huard J
中科院分区：
文献类型：
--
作者：
Takayama K;Kawakami Y;Lavasani M;Mu X;Cummins JH;Yurube T;Kuroda R;Kurosaka M;Fu FH;Robbins PD;Niedernhofer LJ;Huard J
Mice expressing reduced levels of ERCC1‐XPF (Ercc1 −/Δ mice) demonstrate premature onset of age‐related changes due to decreased repair of DNA damage. Muscle‐derived stem/progenitor cells (MDSPCs) isolated from Ercc1 −/Δ mice have an impaired capacity for cell differentiation. The mammalian target of rapamycin (mTOR) is a critical regulator of cell growth in response to nutrient, hormone, and oxygen levels. Inhibition of the mTOR pathway extends the lifespan of several species. Here, we examined the role of mTOR in regulating the MDSPC dysfunction that occurs with accelerated aging. We show that mTOR signaling pathways are activated in Ercc1 −/Δ MDSPCs compared with wild‐type (WT) MDSPCs. Additionally, inhibiting mTOR with rapamycin promoted autophagy and improved the myogenic differentiation capacity of the Ercc1 −/Δ MDSPCs. The percent of apoptotic and senescent cells in Ercc1 −/Δ MDSPC cultures was decreased upon mTOR inhibition. These results establish that mTOR signaling contributes to stem cell dysfunction and cell fate decisions in response to endogenous DNA damage. Therefore, mTOR represents a potential therapeutic target for improving defective, aged stem cells. © 2016 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1375–1382, 2017.
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DOI：
10.18632/aging.100110
发表时间：
2009-12-23
期刊：
Aging
影响因子：
--
作者：
Morselli E;Galluzzi L;Kepp O;Criollo A;Maiuri MC;Tavernarakis N;Madeo F;Kroemer G
通讯作者：
Kroemer G
DOI：
10.1084/jem.20081297
发表时间：
2008-09-29
期刊：
The Journal of experimental medicine
影响因子：
--
作者：
Chen C;Liu Y;Liu R;Ikenoue T;Guan KL;Liu Y;Zheng P
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Zheng P
DOI：
10.3402/pba.v1i0.7219
发表时间：
2011-01-01
期刊：
PATHOBIOLOGY OF AGING AND AGE-RELATED DISEASES
影响因子：
--
作者：
Dolle, Martijn E. T.;Kuiper, Raoul V.;van Steeg, Harry
通讯作者：
van Steeg, Harry
DOI：
10.1002/hep.24713
发表时间：
2012-02
期刊：
Hepatology (Baltimore, Md.)
影响因子：
--
作者：
Gregg SQ;Gutiérrez V;Robinson AR;Woodell T;Nakao A;Ross MA;Michalopoulos GK;Rigatti L;Rothermel CE;Kamileri I;Garinis GA;Stolz DB;Niedernhofer LJ
通讯作者：
Niedernhofer LJ
影响因子：
14.8
作者：
Gharaibeh, Burhan;Lu, Aiping;Huard, Johnny
通讯作者：
Huard, Johnny