The OLD-1 positive regulator of longevity and stress resistance is under DAF-16 regulation in Caenorhabditis elegans

Curr Biol. 2001 Oct 2;11(19):1517-23. doi: 10.1016/s0960-9822(01)00453-5.

Abstract

Aging and limited life span are fundamental biological phenomena observed in a variety of species [1]. Approximately 55 genes have been identified that can extend longevity when altered in Caenorhabditis elegans [2-5]. These genes include an insulin-like receptor (daf-2) and a phosphatidylinositol 3-OH kinase (age-1) regulating a forkhead transcription factor (daf-16) [6, 7], as well as genes mediating metabolic throughput [8], sensory perception [9], and reproduction [10]. Moreover, these mutant alleles both extend life span and increase resistance to ultraviolet (UV) radiation [11], heat [12], and oxidative stress [13-15], though the stress resistance of clk-1 is controversial. With the exception of old-1 and perhaps some other genes [16-19], all of the life-extension alleles are hypomorphic or nullomorphic. Here, we show that the OLD-1 transmembrane tyrosine kinase (formerly TKR-1; [16, 20]) is expressed in a variety of tissues, is stress inducible, and is a positive regulator of longevity and stress resistance. The transcription of old-1 is upregulated in long-lived age-1 and daf-2 mutants and is upregulated in response to heat, UV light, and starvation. Both RT-PCR and analysis of an OLD-1::GFP tag suggest that old-1 expression is dependent on daf-16. Importantly, old-1 is required for the life extension of age-1 and daf-2 mutants. This study reveals a new system for specifying longevity and stress resistance and suggests possible mechanisms for mediating life extension by dietary restriction and hormesis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / enzymology
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / radiation effects
  • Caenorhabditis elegans Proteins / genetics*
  • Caenorhabditis elegans Proteins / metabolism
  • Caenorhabditis elegans Proteins / physiology
  • Forkhead Transcription Factors
  • Gene Expression Regulation, Enzymologic* / radiation effects
  • Heating
  • Helminth Proteins / genetics
  • Helminth Proteins / metabolism
  • Longevity
  • Membrane Proteins / genetics*
  • Phosphatidylinositol 3-Kinases / genetics
  • Protein-Tyrosine Kinases / genetics*
  • Protein-Tyrosine Kinases / metabolism
  • Receptor, Insulin / genetics
  • Receptor, Insulin / metabolism
  • Starvation
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism
  • Transcription Factors / physiology
  • Transcription, Genetic
  • Ultraviolet Rays

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Helminth Proteins
  • Membrane Proteins
  • Transcription Factors
  • daf-16 protein, C elegans
  • Phosphatidylinositol 3-Kinases
  • tkr-1 protein, C elegans
  • AGE-1 protein, C elegans
  • DAF-2 protein, C elegans
  • Protein-Tyrosine Kinases
  • Receptor, Insulin