# Phenotypic and metabonomics studies of FMOs in C. elegans and their roles in lifespan extension

## TL;DR

This study explores how FMO enzymes in C. elegans affect lifespan and metabolism, finding that changes in these enzymes can extend lifespan and alter metabolic profiles.

## Contribution

This is the first systematic study of fmo genetic variation's effect on C. elegans metabolic profiles and lifespan.

## Key findings

- Loss of fmo-4 and fmo-3 and over-expression of fmo-2 increased tryptophan levels and extended lifespan.
- Loss of fmo-4 reduced embryo hatching and increased bleach sensitivity.
- The fmo-1 knockout worm showed no significant metabolite changes despite extended lifespan.

## Abstract

Flavin-Containing Monooxygenases (FMO) are widely conserved, xenobiotic-detoxifying enzymes whose additional endogenous functions have been revealed in recent studies. Those roles include the regulation of longevity in the model nematode Caenorhabditis elegans.

The purpose of this study was to compare aspects of the phenotypes of C. elegans worms with mutations in all fmo genes, particularly focusing on the metabolome and its relationship with lifespan-extension and the worm life cycle. This is the first systematic study of the effect of fmo genetic variation on C. elegans metabolic profiles that we are aware of.

NMR Spectroscopic analysis of the extracts of metabolites from C. elegans worms of different ages and fmo genotypes was used to compare metabolite profiles of C. elegans worms and determine how these changed with genotype and ageing.

Loss of both fmo-4 and fmo-3 and over-expression of fmo-2, resulted in increased levels of tryptophan in the metabolome, which correlated with an extended lifespan in these mutants. Loss of fmo-4 also led to decreased embryo hatching, along with increased sensitivity to bleach during sterilisation protocols. In contrast, in the extended lifespan fmo-1 knockout worm, the metabolome did not reveal any significant metabolite changes and therefore lifespan effects may occur through another mechanism, or hidden metabolic changes.

Genetic interventions coupled with metabolome profiling in C. elegans can provide insights into biological mechanisms in ageing that might lead to strategies for healthy lifespan extension in human old age.

The online version contains supplementary material available at 10.1007/s11306-025-02367-4.