VPS-22/SNF8 regulates longevity via modulating the activity of DAF-16 in C. elegans
VPS-22/SNF8 regulates longevity via modulating the activity of DAF-16 in C. elegans
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VPS-22/SNF8 通过调节线虫中 DAF-16 的活性来调节寿命
DOI：
10.1016/j.bbrc.2020.08.003
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发表时间：
2020
影响因子：
3.1
通讯作者：
Wang Decheng
中科院分区：
文献类型：
--
作者：
Han Shanshan;Lv Yuexia;Wang Jiuxiang;Gao Meng;Yuan Fating;Wang Decheng
衰老受到复杂的信号网络的调节，但其细节仍知之甚少。在这里，我们证明 VPS-22/SNF8（运输-II 所需的内体分选复合体 (ESCRT-II) 的一个组成部分）调节线虫的寿命。在这项研究中，我们发现 vps-22/snf8 基因敲低的蠕虫比野生型蠕虫的寿命更短。线虫中VPS-22/SNF8的表达模式与DAF-16高度相似。敲除线虫中的 daf-16 会缩短线虫的寿命；然而，降低vps-22/snf8indaf-16null蠕虫的表达并没有进一步缩短其寿命，表明vps-22/snf8和daf-16可能通过相同的信号通路作用来调节寿命。 daf-16 的过度表达挽救了 vps-22/snf8 敲低蠕虫的短命表型。此外，vps-22/snf8的下调降低了DAF-16的核定位，并调节了daf-16下游基因的表达，这些基因调节线虫的寿命。总之，我们的结果表明vps-22/snf8可以通过部分调节daf-16的活性来调节线虫的寿命。这些发现可能有助于我们更好地了解衰老的机制。
Aging is regulated by complex signaling networks, the details of which remain poorly understood. Here, we demonstrate that VPS-22/SNF8, a component of endosomal sorting complex required for transport-II (ESCRT-II), regulates the lifespan ofC.áelegans. In this study we show that worms withvps-22/snf8gene knockdown had a shorter lifespan than wild-type worms. The expression pattern of VPS-22/SNF8 inC.áeleganswas highly similar to that of DAF-16. Knockout ofdaf-16inC.áelegansshortened the worms’ lifespan; however, reducing the expression ofvps-22/snf8indaf-16null worms did not further shorten their lifespan, indicating thatvps-22/snf8anddaf-16may act in the same signaling pathway to regulate longevity. Over-expression ofdaf-16rescued the short-lived phenotype ofvps-22/snf8knockdown worms. Moreover, down-regulation ofvps-22/snf8decreased the nuclear localization of DAF-16 and modulated the expression ofdaf-16downstream genes that regulate longevity inC.áelegans. In summary, our results indicate thatvps-22/snf8can regulate the longevity ofC.áelegansby partially modulating the activity ofdaf-16. These findings may help us to better understand the mechanisms of aging.