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Introduction <p>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 <i>Caenorhabditis elegans.</i></p> Objectives <p>The purpose of this study was to compare aspects of the phenotypes of <i>C. elegans</i> worms with mutations in all <i>fmo</i> 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 <i>fmo</i> genetic variation on <i>C. elegans</i> metabolic profiles that we are aware of.</p> Methods <p>NMR Spectroscopic analysis of the extracts of metabolites from <i>C. elegans</i> worms of different ages and <i>fmo</i> genotypes was used to compare metabolite profiles of <i>C. elegans</i> worms and determine how these changed with genotype and ageing.</p> Results <p>Loss of both <i>fmo-4</i> and <i>fmo-3</i> and over-expression of <i>fmo-</i>2, resulted in increased levels of tryptophan in the metabolome, which correlated with an extended lifespan in these mutants. Loss of <i>fmo-4</i> also led to decreased embryo hatching, along with increased sensitivity to bleach during sterilisation protocols. In contrast, in the extended lifespan <i>fmo-1</i> knockout worm, the metabolome did not reveal any significant metabolite changes and therefore lifespan effects may occur through another mechanism, or hidden metabolic changes.</p> Conclusion <p>Genetic interventions coupled with metabolome profiling in <i>C. elegans</i> can provide insights into biological mechanisms in ageing that might lead to strategies for healthy lifespan extension in human old age.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年11月15日

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  • Mohamed Said,
  • Rafael Freire,
  • Filipe Cabreiro,
  • Jose Ivan Serrano-Contreras,
  • Elinor P. Thompson,
  • Jeremy R. Everett

摘要

Introduction

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.

Objectives

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.

Methods

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.

Results

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.

Conclusion

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.