Na Hyun-Jin, Pyo Jung-Hoon, Jeon Ho-Jun, Park Joung-Sun, Chung Hae-Young, Yoo Mi-Ae
Department of Molecular Biology, Pusan National University, Busan, Republic of Korea.
Molecular Inflammation Research Center for Aging Intervention (MRCA), College of Pharmacy, Pusan National University, Busan, Republic of Korea.
Biochem Biophys Res Commun. 2018 Mar 25;498(1):18-24. doi: 10.1016/j.bbrc.2018.02.191. Epub 2018 Feb 27.
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.
成体干细胞与年龄相关的变化对于组织衰老和年龄相关疾病至关重要。因此，阐明预防成体干细胞衰老的机制对于健康衰老不可或缺。二甲双胍作为一种治疗2型糖尿病的药物，因其抗衰老和抗癌作用而受到关注。在果蝇肠道干细胞（ISC）中，我们之前报道了二甲双胍对ISC与年龄相关表型的抑制作用。在此，我们表明，在ISC中敲低关键的自噬相关因子Atg6会诱导ISC出现与年龄相关的表型，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依赖的方式抑制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衰老作用所必需的，这为二甲双胍对成体干细胞衰老的干预机制提供了依据。
