Transcriptional analysis of C. elegans fmos at different life stages and their roles in ageing
Author(s)
Type
Journal Article
Abstract
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.
Date Issued
2024-12-05
Date Acceptance
2024-10-22
Citation
Molecular Genetics and Genomics, 2024, 299
ISSN
1617-4615
Publisher
Springer
Journal / Book Title
Molecular Genetics and Genomics
Volume
299
Copyright Statement
© The Author(s) 2024 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/39636438
PII: 10.1007/s00438-024-02201-x
Subjects
C. elegans worms
Flavin-containing monooxygenases (FMOs)
Gene mutation
Lifespan
Transcription
Animals
Caenorhabditis elegans
Oxygenases
Aging
Longevity
Humans
Caenorhabditis elegans Proteins
Mice
Gene Knockout Techniques
Life Cycle Stages
Gene Expression Profiling
Publication Status
Published
Coverage Spatial
Germany
Article Number
113
Date Publish Online
2024-12-05