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Autophagy maintains stemness by preventing senescence

机译：自噬通过防止衰老来保持干性

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摘要

During ageing, muscle stem-cell regenerative function declines. At advanced geriatric age, this decline is maximal owing to transition from a normal quiescence into an irreversible senescence state. How satellite cells maintain quiescence and avoid senescence until advanced age remains unknown. Here we report that basal autophagy is essential to maintain the stem-cell quiescent state in mice. Failure of autophagy in physiologically aged satellite cells or genetic impairment of autophagy in young cells causes entry into senescence by loss of proteostasis, increased mitochondrial dysfunction and oxidative stress, resulting in a decline in the function and number of satellite cells. Re-establishment of autophagy reverses senescence and restores regenerative functions in geriatric satellite cells. As autophagy also declines in human geriatric satellite cells, our findings reveal autophagy to be a decisive stem-cell-fate regulator, with implications for fostering muscle regeneration in sarcopenia.
机译：在衰老期间，肌肉干细胞的再生功能下降。在老年老年期，由于从正常的静止状态过渡到不可逆的衰老状态，这种下降最大。卫星细胞如何保持静止并避免衰老直到高龄尚不清楚。在这里我们报道基础自噬对维持小鼠干细胞的静止状态至关重要。生理上老化的卫星细胞中自噬的失败或年轻细胞中自噬的遗传损伤会导致蛋白质变性丧失，线粒体功能障碍和氧化应激增加，从而导致衰老，从而导致卫星细胞的功能和数量下降。自噬的重建逆转衰老，并恢复老年卫星细胞的再生功能。由于人类老年性卫星细胞中的自噬也下降，因此我们的发现表明自噬是决定性的干细胞命运调节剂，对促进少肌症的肌肉再生具有重要意义。

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  • 来源
    《Nature》 |2016年第7584期|37-42|共6页
  • 作者

    Garcia-Prat Laura; Martinez-Vicente Marta; Perdiguero Eusebio; Ortet Laura; Rodriguez-Ubreva Javier; Rebollo Elena; Ruiz-Bonilla Vanessa; Gutarra Susana; Ballestar Esteban; Serrano Antonio L.; Sandri Marco; Munoz-Canoves Pura;

  • 作者单位

    Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain;

    Vall dHebron Res Inst, Neurodegenerat Dis Res Grp, CIBERNED, E-08035 Barcelona, Spain;

    Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain;

    Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain;

    Bellvitge Biomed Res Inst IDIBELL, Chromatin & Dis Grp, Canc Epigenet & Biol Programme PEBC, E-08907 Lhospitalet De Llobregat, Spain;

    CSIC, Adv Fluorescence Microscopy Unit, Mol Biol Inst Barcelona IBMB, E-08028 Barcelona, Spain;

    Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain;

    Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain;

    Bellvitge Biomed Res Inst IDIBELL, Chromatin & Dis Grp, Canc Epigenet & Biol Programme PEBC, E-08907 Lhospitalet De Llobregat, Spain;

    Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain;

    Univ Padua, Dept Biomed Sci, I-35100 Padua, Italy|Telethon Inst Genet & Med TIGEM, I-80131 Naples, Italy;

    Pompeu Fabra Univ UPF, Cell Biol Grp, Dept Expt & Hlth Sci, CIBER Neurodegenerat Dis CIBERNED, E-08003 Barcelona, Spain|ICREA, E-08908 Barcelona, Spain;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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