Dietary restriction, which extends life and increases resistance to a variety of stresses, can be studied in C. elegans using the eating defective mutant
eat-2(
ad1116)(1).
eat-2(
ad1116) animals pump slowly and therefore ingest less food, despite inhabiting a full food environment.
eat-2(
ad1116) mutants live ~15-30 percent longer than N2 worms. A cDNA microarray study comparing
eat-2(
ad1116) to N2 worms revealed an overrepresentation of the transcription factor SKN-1 binding site in food intake-regulated genes. SKN-1 functions in early embryogenesis to influence development of the digestive tract and in adults as a stress response protein (2). We determined that
eat-2(
ad1116)
rrf-3(
pk1426)s longevity depends on SKN-1, as RNAi of
skn-1 preferentially shortens lifespan compared to
rrf-3(
pk1426) controls. We also found, using
skn-1 RNAi, that
eat-2(
ad1116)
rrf-3(
pk1426) upregulates expression of the putative alcohol dehydrogenase
dod-11 (a reporter of nutritional status) in a SKN-1-dependent manner. Further, we report that SKN-1 is required for
eat-2(
ad1116)s unusual response to whole gonad ablation. Specifically, whereas wild-type animals exhibit no change in lifespan in response to laser ablation of the gonadal precursor cells Z1 and Z4,
eat-2(
ad1116) lives long when Z1 and Z4 are ablated. RNAi of
skn-1 eliminates this
eat-2(
ad1116)-specific effect. SKN-1::GFP localizes to nuclei in response to various stressors, including heat and oxidative damage (2). Interestingly, we detected no visible change in expression levels or localization of SKN-1::GFP in an
eat-2(
ad1116) background, suggesting that either little or no SKN-1 is mobilized in an
eat-2(
ad1116) context, or that SKN-1 exerts its longevity-promoting effects independent of visible nuclear translocation. In summary, we demonstrate a role for SKN-1 in
eat-2(
ad1116)
rrf-3(
pk1426) longevity and are continuing our investigations. (1) Lakowski and Hekimi, PNAS 1998 (2) An and Blackwell, Genes Dev 2003.