Research Paper Volume 3, Issue 2 pp 125—147
Modulation of lipid biosynthesis contributes to stress resistance and longevity of C. elegans mutants
- 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
Received: February 3, 2011 Accepted: February 24, 2011 Published: February 25, 2011
https://doi.org/10.18632/aging.100275How to Cite
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.
Abbreviations
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.