Said, Mohamed, Ferrara, Bill T. ORCID: https://orcid.org/0000-0002-2163-4032, Aprodu, Andrea, Cabreiro, Filipe, Thompson, Elinor P. ORCID: https://orcid.org/0000-0002-6434-9290 and Everett, Jeremy (2024) Transcriptional analysis of C. elegans fmos at different life stages and their roles in ageing. Molecular Genetics and Genomics, 299:113. ISSN 1617-4615 (Print), 1617-4623 (Online) (doi:10.1007/s00438-024-02201-x)

Preview	PDF (Open Access Article) 48400 THOMPSON_Transcriptional_Analysis_Of_C_Elegans_Fmos_At_Different_Life_Stages_And_Their_Roles_In_Ageing_(OA)_2024.pdf - Published Version Available under License Creative Commons Attribution. Download (1MB) | Preview
Preview	PDF (Author's Accepted Manuscript) 48400 THOMPSON_Transcriptional_Analysis_Of_C_Elegans_Fmos_At_Different_Life_Stages_And_Their_Roles_In_Ageing_(AAM)_2024.pdf - Accepted Version Available under License Creative Commons Attribution. Download (513kB) | Preview
	PDF (Supplemental material) 48400 THOMPSON_Transcriptional_Analysis_Of_C_Elegans_Fmos_At_Different_Life_Stages_And_Their_Roles_In_Ageing_(SUPPLEMENTARY)_2024.pdf - Supplemental Material Restricted to Repository staff only Download (2MB) | Request a copy

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.

Item Type:	Article
Uncontrolled Keywords:	ageing, C. elegans, flavin monooxygenase
Subjects:	Q Science > Q Science (General)
Faculty / School / Research Centre / Research Group:	Faculty of Engineering & Science Faculty of Engineering & Science > School of Science (SCI)
Last Modified:	10 Dec 2024 11:32
URI:	http://gala.gre.ac.uk/id/eprint/48400

Actions (login required)

View Item

Downloads