SUMOylation, a conserved protein post-translational modification that performs multiple functions including regulation of nuclear transport and transcription, is implicated in numerous biological processes including aging. RNAi knockdown of the sole Small Ubiquitin-like MOdifier (SUMO) gene, smo-1, in Caenorhabditis elegans shortened lifespan, whereas overexpression in the intestine modestly increased lifespan. Smo-1 is required for mitochondrial fission in a tissue-specific manner. Fission, in turn, is needed for mitophagy to maintain mitochondrial homeostasis during aging. SUMOlyation affects DAuer Formation (DAF)-16, which can be directly SUMOylated, and SKN-1, the homolog of mammalian Nrf2. These regulators play key roles in maintaining mitochondrial homeostasis. However, given the modest effect of overexpressing smo-1 on lifespan enhancement and potential interference with other genes that can promote increased lifespan, caution is advised in the translation of this study based on C. elegans. Although inhibitors of SUMOlyation have been developed for cancer and activators also have been identified, broad-acting biochemical pathway modifiers such as SUMO are often suboptimal drug targets and may not be as promising for antiaging applications as they first appear.

中文翻译：

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SUMO 与 Mitophagy 搏斗以延长寿命

SUMOylation 是一种保守的蛋白质翻译后修饰，具有多种功能，包括调节核转运和转录，与包括衰老在内的许多生物过程有关。秀丽隐杆线虫中唯一的小泛素样修饰符 (SUMO) 基因 smo-1 的 RNAi 敲低寿命缩短，而肠道中的过度表达适度延长寿命。Smo-1 是组织特异性方式的线粒体裂变所必需的。反过来，线粒体自噬需要裂变以在衰老过程中维持线粒体稳态。SUMOlyation 影响 DAuer Formation (DAF)-16，它可以直接被 SUMOylated，以及 SKN-1，哺乳动物 Nrf2 的同系物。这些调节剂在维持线粒体稳态方面发挥着关键作用。然而，鉴于过度表达 smo-1 对延长寿命的影响不大，并且可能干扰其他可促进延长寿命的基因，因此建议在翻译这项基于秀丽隐杆线虫的研究时要谨慎. 尽管已经开发出用于癌症的 SUMOlyation 抑制剂和激活剂，但诸如 SUMO 之类的广泛作用的生化途径调节剂通常是次优的药物靶标，并且可能不像它们最初出现的那样有希望用于抗衰老应用。