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Updated: May 13, 2026

Measuring Caenorhabditis elegans Life Span in 96 Well Microtiter Plates
12:23

Measuring Caenorhabditis elegans Life Span in 96 Well Microtiter Plates

Published on: March 18, 2011

Lifespan extension induced by AMPK and calcineurin is mediated by CRTC-1 and CREB

William Mair1, Ianessa Morantte, Ana P C Rodrigues

  • 1The Salk Institute for Biological Studies, La Jolla, California 92037, USA.

Nature
|February 19, 2011
PubMed

Insights

Activating AMPK or inactivating calcineurin extends lifespan by modifying CRTC-1, a protein crucial for longevity. This pathway involves CRTC-1 and CRH-1, offering new therapeutic targets for age-related diseases.

Area of Science:

  • Molecular Biology
  • Genetics
  • Aging Research

Background:

  • AMPK activation and calcineurin inactivation are known to slow aging in C. elegans.
  • These pathways are implicated as therapeutic targets for age-related diseases in mammals.
  • The direct molecular targets mediating these longevity effects remain largely unknown.

Purpose of the Study:

  • To identify the direct targets of AMPK and calcineurin that regulate longevity.
  • To elucidate the molecular mechanisms by which these pathways influence lifespan.
  • To investigate the role of CREB-regulated transcriptional coactivators (CRTCs) in aging.

Main Methods:

  • Utilized C. elegans as a model organism.
  • Investigated the interaction between AMPK, calcineurin, CRTC-1, and CRH-1.
  • Analyzed transcriptional responses and lifespan modifications through gene manipulation (downregulation).

Main Results:

  • AMPK and calcineurin modulate longevity exclusively via post-translational modification of CRTC-1.
  • CRTC-1 is a direct AMPK target and interacts with the transcription factor CRH-1.
  • Reduced CRTC-1 or CRH-1 activity mimics the pro-longevity effects of AMPK activation or calcineurin inactivation.

Conclusions:

  • CRTC-1 and CRH-1 play a novel, critical role in determining lifespan downstream of AMPK and calcineurin.
  • This conserved pathway illustrates how low energy signals can increase longevity.
  • Findings suggest CRTCs and CREB as potential therapeutic targets for aging and age-related pathologies.

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