Said Mohamed, Ferrara Bill T, Aprodu Andreea, Cabreiro Filipe, Thompson Elinor P, Everett Jeremy
Faculty of Engineering and Science, University of Greenwich, Chatham Maritime, Kent, ME4 4TB, UK.
Faculty of Pharmacy, October University for Modern Sciences and Arts, 6th October City, Egypt.
Mol Genet Genomics. 2024 Dec 5;299(1):113. doi: 10.1007/s00438-024-02201-x.
Flavin-containing monooxygenases (FMOs) are present in most organisms including plants, fungi, bacteria, invertebrates and vertebrates, where they catalyse the oxidative metabolism of a range of xenobiotics and endogenous metabolites. FMOs have been associated with ageing and longevity in the mouse and in C. elegans. As all five FMOs of C. elegans share an evolutionary root with mouse and human FMO5, it was of interest to discover if effects on ageing and longevity persisted across the whole group. We therefore investigated the impact of fmo gene knockout (KO) in C. elegans. We found that fmo-1, fmo-3 and fmo-4 KO significantly extended C. elegans lifespan relative to wild type and, as previously reported, FMO-2 over-expression did likewise. The transcription levels of C. elegans fmo genes were determined throughout the life cycle (embryo, larva and adult) in wild type and in each mutant to discover if their expression was related to stages in ageing, and expression levels were compared to those in human and mouse. In wild type worms, fmo-1 and fmo-4 were the mostly highly transcribed genes (especially at the larval stage), whereas fmo-2 and fmo-3 were the least transcribed, at all stages. Notably, the knockout of fmo-4 led to a 17- to 30-fold up-regulation of fmo-2, along with significantly increased levels of the other fmos. This parallels recent findings in the long-lived C. elegans tald-1 mutant where fmo-2 was also significantly up-regulated and reinforces its importance in lifespan extension.
含黄素单加氧酶（FMOs）存在于大多数生物体中，包括植物、真菌、细菌、无脊椎动物和脊椎动物，在这些生物体中，它们催化一系列外源性物质和内源性代谢物的氧化代谢。FMOs与小鼠和秀丽隐杆线虫的衰老和寿命有关。由于秀丽隐杆线虫的所有五种FMOs与小鼠和人类的FMO5有着共同的进化根源，因此探究对衰老和寿命的影响是否在整个群体中持续存在很有意义。因此，我们研究了秀丽隐杆线虫中fmo基因敲除（KO）的影响。我们发现，相对于野生型，fmo-1、fmo-3和fmo-4基因敲除显著延长了秀丽隐杆线虫的寿命，并且如先前报道的那样，FMO-2的过表达也有同样的效果。我们测定了野生型和每个突变体在整个生命周期（胚胎、幼虫和成虫）中秀丽隐杆线虫fmo基因的转录水平，以发现它们的表达是否与衰老阶段相关，并将表达水平与人类和小鼠的进行比较。在野生型线虫中，fmo-1和fmo-4是转录水平最高的基因（尤其是在幼虫阶段），而fmo-2和fmo-3在所有阶段的转录水平最低。值得注意的是，fmo-4基因敲除导致fmo-2上调17至30倍，同时其他fmo的水平也显著增加。这与长寿的秀丽隐杆线虫tald-1突变体的最新研究结果相似，在该突变体中fmo-2也显著上调，并强化了其在寿命延长中的重要性。
