Transcriptional analysis of C. elegans fmos at different life stages and their roles in ageing.

Publisher: Springer-Verlag Country of Publication: Germany NLM ID: 101093320 Publication Model: Electronic Cited Medium: Internet ISSN: 1617-4623 (Electronic) Linking ISSN: 16174623 NLM ISO Abbreviation: Mol Genet Genomics Subsets: MEDLINE

Original Publication: Berlin : Springer-Verlag, c2001-

Caenorhabditis elegans*/genetics ; Caenorhabditis elegans*/growth & development ; Oxygenases*/genetics ; Oxygenases*/metabolism ; Aging*/genetics ; Longevity*/genetics; Animals ; Humans ; Caenorhabditis elegans Proteins/genetics ; Caenorhabditis elegans Proteins/metabolism ; Mice ; Gene Knockout Techniques ; Life Cycle Stages/genetics ; Gene Expression Profiling/methods

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.
Competing Interests: Declarations. Competing interests: Dr M. Said is a founder and CSO of Rapid Biolabs an AI company involved in C. elegans and other imaging. The other authors declare no conflicts of interest.
(© 2024. The Author(s).)

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United Kingdom WT_ Wellcome Trust

Keywords: C. elegans worms; Flavin-containing monooxygenases (FMOs); Gene mutation; Lifespan; Transcription

EC 1.13.- (Oxygenases)
EC 1.14.13.8 (dimethylaniline monooxygenase (N-oxide forming))
0 (Caenorhabditis elegans Proteins)

Date Created: 20241205 Date Completed: 20241205 Latest Revision: 20241208

20241209

PMC11621177

10.1007/s00438-024-02201-x

39636438