RRC ID 6399
Author Mair W, Panowski SH, Shaw RJ, Dillin A.
Title Optimizing dietary restriction for genetic epistasis analysis and gene discovery in C. elegans.
Journal PLoS ONE
Abstract Dietary restriction (DR) increases mammalian lifespan and decreases susceptibility to many age-related diseases. Lifespan extension due to DR is conserved across a wide range of species. Recent research has focused upon genetically tractable model organisms such as C. elegans to uncover the genetic mechanisms that regulate the response to DR, in the hope that this information will provide insight into the mammalian response and yield potential therapeutic targets. However, no consensus exists as to the best protocol to apply DR to C. elegans and potential key regulators of DR are protocol-specific. Here we define a DR method that better fulfills criteria required for an invertebrate DR protocol to mirror mammalian studies. The food intake that maximizes longevity varies for different genotypes and informative epistasis analysis with another intervention is only achievable at this 'optimal DR' level. Importantly therefore, the degree of restriction imposed using our method can easily be adjusted to determine the genotype-specific optimum DR level. We used this protocol to test two previously identified master regulators of DR in the worm. In contrast to previous reports, we find that DR can robustly extend the lifespan of worms lacking the AMP-activated protein kinase catalytic subunit AAK2 or the histone deacetylase SIR-2.1, highlighting the importance of first optimizing DR to identify universal regulators of DR mediated longevity.
Volume 4(2)
Pages e4535
Published 2009
DOI 10.1371/journal.pone.0004535
PMID 19229346
PMC PMC2643252
MeSH Animals Caenorhabditis elegans / genetics* Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / physiology Caloric Restriction* Epistasis, Genetic* Genes, Helminth* Longevity / genetics Protein-Serine-Threonine Kinases / genetics* Protein-Serine-Threonine Kinases / physiology Sirtuins / genetics* Sirtuins / physiology
IF 2.766
Times Cited 45
C.elegans tm1944