Questions, Feedback & Help
Send us an email and we'll get back to you ASAP. Or you can read our Frequently Asked Questions.
  • page settings
  • hide sidebar
  • show empty fields
  • layout
  • (too narrow)
  • open all
  • close all
Resources » Paper

Steinbaugh, Michael J. et al. (2013) International Worm Meeting "Regulation of SKN-1/Nrf by the germline longevity pathway."

  • History

  • Referenced

  • Tree Display

  • My Favorites

  • My Library

  • Comments on Steinbaugh, Michael J. et al. (2013) International Worm Meeting "Regulation of SKN-1/Nrf by the germline longevity pathway." (0)

  • Overview

    Status:
    Publication type:
    Meeting_abstract
    WormBase ID:
    WBPaper00043031

    Steinbaugh, Michael J., Narasimhan, Sri Devi, Robida-Stubbs, Stacey, Raghavan, Prashant, Operana, Theresa, & Blackwell, T. Keith (2013). Regulation of SKN-1/Nrf by the germline longevity pathway presented in International Worm Meeting. Unpublished information; cite only with author permission.

    In C. elegans, a reduction in germline stem cell (GSC) number increases lifespan and stress resistance through a longevity pathway that seems to be distinct from those related to nutrient sensing and metabolism (e.g. insulin/IGF-1 signaling, the TOR pathway, mitochondrial function, and dietary restriction). The GSC pathway is a tissue non-autonomous regulator of longevity that is known to involve the transcription factors DAF-16, DAF-12, and NHR-80 in the intestine. We recently determined that the transcription factor SKN-1 (Nrf in mammals) is also regulated by this pathway. The germline can be removed through laser ablation or genetic disruption of the Notch ortholog GLP-1. Using skn-1(zu135), skn-1 RNAi, and temperature-sensitive glp-1(bn18) mutants, we determined that skn-1 is required for lifespan extension associated with GSC removal. In contrast to DAF-16, SKN-1 is also required for the associated increase in oxidative stress resistance (e.g. sodium arsenite, tert-butylhydroperoxide). We found that SKN-1 accumulates in intestinal nuclei when GSC number is reduced, and that this is partially dependent upon KRI-1, an ankryin repeat protein implicated in regulation of DAF-16 by this pathway. Using qRT-PCR and analysis of transcriptional reporters, we determined that multiple SKN-1 target genes (e.g. gst-4, gcs-1, nit-1, and F20D6.11) are transcriptionally upregulated in germline-deficient animals in a SKN-1-dependent manner. This distinctive longevity pathway provides an exciting example of environmental sensing and signaling from the reproductive stem cell niche. Current efforts are aimed at understanding how the GSC pathway regulates SKN-1, and identifying processes controlled by SKN-1 in this context.

    Affiliations:
    - Harvard Stem Cell Institute, and Department of Genetics, Harvard Medical School, Boston, MA.
    - Islet Cell & Regenerative Biology, Joslin Diabetes Center, Boston, MA.


    Tip: Seeing your name marked red? Please help us identify you.