Deficiency of Atg6 impairs beneficial effect of metformin on intestinal stem cell aging in Drosophila
Deficiency of Atg6 impairs beneficial effect of metformin on intestinal stem cell aging in Drosophila
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DOI：
10.1016/j.bbrc.2018.02.191
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发表时间：
2018-03-25
影响因子：
3.1
通讯作者：
Yoo, Mi-Ae
中科院分区：
文献类型：
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作者：
Na, Hyun-Jin;Pyo, Jung-Hoon;Yoo, Mi-Ae
成体干细胞的衰老相关变化对组织衰老和年龄相关疾病至关重要。因此，阐明防止成体干细胞衰老的机制对于健康衰老是必不可少的。二甲双胍是一种治疗2型糖尿病的药物，因其抗衰老和抗癌作用而备受关注。在果蝇肠干细胞（ISC）中，我们先前报道了二甲双胍对ISC年龄相关表型的抑制作用。在这里，我们发现，Atg6，一个重要的自噬相关因子，在ISC中的敲低诱导年龄相关的表型ISC，如过度增殖，中心体扩增，和DNA损伤积累。然后，我们发现二甲双胍以Atg6依赖性方式抑制ISC衰老表型。综上所述，我们的研究表明，Atg6是二甲双胍抑制ISC衰老所必需的，提供了二甲双胍对成体干细胞衰老的干预机制。(C)2018爱思唯尔公司All rights reserved.
Age-related changes of adult stem cell are crucial for tissue aging and age-related diseases. Thus, clarifying mechanisms to prevent adult stem cell aging is indispensable for healthy aging. Metformin, a drug for type 2 diabetes, has been highlighted for its anti-aging and anti-cancer effect. In Drosophila intestinal stem cell (ISC), we previously reported the inhibitory effect of metformin on age-related phenotypes of ISC. Here, we showed that knockdown of Atg6, a crucial autophagy-related factor, in ISC induces age related phenotypes of ISC such as hyperproliferation, centrosome amplification, and DNA damage accumulation. Then, we revealed that metformin inhibits ISC aging phenotypes in Atg6-dependent manner. Taken together, our study suggests that Atg6 is required for the inhibitory effect of metformin on ISC aging, providing an intervention mechanism of metformin on adult stem cell aging. (C) 2018 Elsevier Inc. All rights reserved.