Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants

Robert J. Shmookler Reis, Lulu Xu, Hoonyong Lee, Minho Chae, John J. Thaden, Puneet Bharill, Cagdas Tazearslan, Eric Siegel, Ramani Alla, Piotr Zimniak, Srinivas Ayyadevara

Research output: Contribution to journalArticle

93 Scopus citations

Abstract

Many lifespan-modulating genes are involved in either generation of oxidative substrates and end-products, or their detoxification and removal. Among such metabolites, only lipoperoxides have the ability to produce free-radical chain reactions. For this study, fatty-acid profiles were compared across a panel of C. elegans mutants that span a tenfold range of longevities in a uniform genetic background. Two lipid structural properties correlated extremely well with lifespan in these worms: fatty-acid chain length and susceptibility to oxidation both decreased sharply in the longest-lived mutants (affecting the insulinlike-signaling pathway). This suggested a functional model in which longevity benefits from a reduction in lipid peroxidation substrates, offset by a coordinate decline in fatty-acid chain length to maintain membrane fluidity. This model was tested by disrupting the underlying steps in lipid biosynthesis, using RNAi knockdown to deplete transcripts of genes involved in fatty-acid metabolism. These interventions produced effects on longevity that were fully consistent with the functions and abundances of their products. Most knockdowns also produced concordant effects on survival of hydrogen peroxide stress, which can trigger lipoperoxide chain reactions.

Original languageEnglish (US)
Pages (from-to)125-147
Number of pages23
JournalAging
Volume3
Issue number2
DOIs
StatePublished - Feb 2011

Keywords

  • Aging
  • Lipid (Fatty Acid)
  • Lipoperoxidation
  • Longevity
  • Nematode
  • RNAi

ASJC Scopus subject areas

  • Aging
  • Cell Biology

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    Shmookler Reis, R. J., Xu, L., Lee, H., Chae, M., Thaden, J. J., Bharill, P., Tazearslan, C., Siegel, E., Alla, R., Zimniak, P., & Ayyadevara, S. (2011). Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants. Aging, 3(2), 125-147. https://doi.org/10.18632/aging.100275