Journal article
Insulin-like signaling determines survival during stress via posttranscriptional mechanisms in C. elegans
G McColl, AN Rogers, S Alavez, AE Hubbard, S Melov, CD Link, AI Bush, P Kapahi, GJ Lithgow
Cell Metabolism | CELL PRESS | Published : 2010
Abstract
The insulin-like signaling (ILS) pathway regulates metabolism and is known to modulate adult life span in C. elegans. Altered stress responses and resistance to a wide range of stressors are also associated with changes in ILS and contribute to enhanced longevity. The transcription factors DAF-16 and HSF-1 are key effectors of the longevity phenotype. We demonstrate that increased intrinsic thermotolerance, due to lower ILS, is not dependent on stress-induced transcriptional responses but instead requires active protein translation. Translation profiling experiments reveal genes that are posttranscriptionally regulated in response to altered ILS during heat shock in a DAF-16-dependent manner..
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Awarded by National Institutes of Health
Funding Acknowledgements
We thank Krysta Felkey, Richard M. Neve, Gary K. Scott, and Nicole L. Jenkins for technical advice and critical comments. Some nematode strains used in this work were provided by the Caenorhabditis Genetics Center (University of Wisconsin), which is funded by the NIH National Center for Research Resources (NCRR). Knockout strains were provided by the C. elegans Reverse Genetics Core Facility (UBC, Canada) and the International C. elegans Gene Knockout Consortium. The COPAS BIOSORT system was a gift from The Glenn Foundation for Medical Research and The Herbert Simon Foundation. G.M. was supported by the Glenn Foundation for Medical Research/American Federation for Aging Research. G.J.L. is supported by the NIH AG21069, AG22868, AG029631-01A1, ES016655, the Larry L. Hillblom Foundation, and UL1 RR024917. Array studies were supported by a Nathan Shock Center award to the Buck Institute, AG025798, and a Glenn award to S.M. from the Glenn foundation for Medical Research. G.M. planned and designed the project with consultation and support from P.K. and G.J.L. C.D.L. and A.I.B. provided material support. Gene expression studies were designed and carried out by G.M. and S.M., and the TSA study was designed by G.M., A.N.R., P.K., and G.J.L. and analyzed by G.M., A.E.H., and S.M. in the Genomics Core (Buck Institute). All other data were collected by G.M., with assistance from S.A. G.M. wrote the paper with contribution from all authors. P.K. was additionally supported by AG032113, AG031337, and the Larry L. Hillblom Foundation.