The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans

  1. Javier Apfeld1,
  2. Greg O'Connor,
  3. Tom McDonagh,
  4. Peter S. DiStefano, and
  5. Rory Curtis
  1. Elixir Pharmaceuticals, Cambridge, Massachusetts 02139, USA

Abstract

Although limiting energy availability extends lifespan in many organisms, it is not understood how lifespan is coupled to energy levels. We find that the AMP:ATP ratio, a measure of energy levels, increases with age in Caenorhabditis elegans and can be used to predict life expectancy. The C. elegans AMP-activated protein kinase α subunit AAK-2 is activated by AMP and functions to extend lifespan. In addition, either an environmental stressor that increases the AMP:ATP ratio or mutations that lower insulin-like signaling extend lifespan in an aak-2-dependent manner. Thus, AAK-2 is a sensor that couples lifespan to information about energy levels and insulin-like signals.

Keywords

Footnotes

  • Supplemental material is available at http://www.genesdev.org.

  • Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1255404.

  • 1 Corresponding author. E-MAIL japfeld{at}elixirpharm.com; FAX (617) 995-7014.

    • Accepted October 18, 2004.
    • Received August 27, 2004.
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