Research Paper Volume 3, Issue 2 pp 125—147

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

Robert J. Shmookler Reis1,2,3, , Lulu Xu2, , Hoonyong Lee2, , Minho Chae2, *, , John J. Thaden2, , Puneet Bharill1,3, , Cagdas Tazearslan3, , , Eric Siegel4, , Ramani Alla1, , Piotr Zimniak1,5, , Srinivas Ayyadevara1,2, ,

  • 1 Central Arkansas Veterans Healthcare Service, Little Rock, AR 72205, USA
  • 2 Department of Geriatrics, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
  • 3 Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
  • 4 Department of Biostatistics University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
  • 5 Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA
* National Center for Toxicologic Research, Jefferson, AR, USA
† Dept. of Genetics, Albert Einstein College of Medicine, Bronx NY 10461 USA

Received: February 3, 2011       Accepted: February 24, 2011       Published: February 25, 2011
How to Cite

Copyright: © 2011 Shmookler Reis et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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.


ACL: average chain length; DBI: double bond index; FA: fatty acid; FAME: fatty acid methyl ester; GC-MS: gas chromatography - mass spectrometry; IIS: insulin/insulinlike growth factor-1 signaling; mmBC: monomethyl branched-chain; MUFA: monounsaturated fatty acid; PI: peroxidation index; PUFA: polyunsaturated fatty acid; RT-PCR: real-time reverse transcriptase PCR.