秀丽隐杆线虫幼虫静止期诱导产生的可逆性衰老相关表型。
Reversible Age-Related Phenotypes Induced during Larval Quiescence in C. elegans.
作者信息
Roux Antoine E, Langhans Kelley, Huynh Walter, Kenyon Cynthia
机构信息
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA; Calico Life Sciences, 1170 Veterans Boulevard, South San Francisco, CA 94080, USA.
Department of Biochemistry and Biophysics, University of California, San Francisco, 600 16th Street, San Francisco, CA 94158-2517, USA.
出版信息
Cell Metab. 2016 Jun 14;23(6):1113-1126. doi: 10.1016/j.cmet.2016.05.024.
Cells can enter quiescent states in which cell cycling and growth are suspended. We find that during a long developmental arrest (quiescence) induced by starvation, newly hatched C. elegans acquire features associated with impaired proteostasis and aging: mitochondrial fission, ROS production, protein aggregation, decreased proteotoxic-stress resistance, and at the organismal level, decline of mobility and high mortality. All signs of aging but one, the presence of protein aggregates, were reversed upon return to development induced by feeding. The endoplasmic reticulum receptor IRE-1 is completely required for recovery, and the downstream transcription factor XBP-1, as well as a protein kinase, KGB-1, are partially required. Interestingly, kgb-1(-) mutants that do recover fail to reverse aging-like mitochondrial phenotypes and have a short adult lifespan. Our study describes the first pathway that reverses phenotypes of aging at the exit of prolonged quiescence.
细胞可以进入静止状态，在此状态下细胞周期和生长会暂停。我们发现，在由饥饿诱导的长期发育停滞（静止）期间，新孵化的秀丽隐杆线虫会获得与蛋白质稳态受损和衰老相关的特征：线粒体分裂、活性氧产生、蛋白质聚集、蛋白质毒性应激抗性降低，在生物体水平上，运动能力下降和高死亡率。除了蛋白质聚集体的存在这一衰老迹象外，所有衰老迹象在恢复进食诱导的发育后都得到了逆转。内质网受体IRE-1是恢复所完全必需的，下游转录因子XBP-1以及蛋白激酶KGB-1则是部分必需的。有趣的是，确实恢复的kgb-1(-)突变体无法逆转衰老样线粒体表型，并且成年寿命较短。我们的研究描述了第一个在长期静止结束时逆转衰老表型的途径。
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