Signals from the reproductive system regulate the lifespan of C. elegans

Nature. 1999 May 27;399(6734):362-6. doi: 10.1038/20694.


Understanding how the ageing process is regulated is a fascinating and fundamental problem in biology. Here we demonstrate that signals from the reproductive system influence the lifespan of the nematode Caenorhabditis elegans. If the cells that give rise to the germ line are killed with a laser microbeam, the lifespan of the animal is extended. Our findings suggest that germline signals act by modulating the activity of an insulin/IGF-1 (insulin-like growth factor) pathway that is known to regulate the ageing of this organism. Mutants with reduced activity of the insulin/IGF-1-receptor homologue DAF-2 have been shown to live twice as long as normal, and their longevity requires the activity of DAF- 16, a member of the forkhead/winged-helix family of transcriptional regulators. We find that, in order for germline ablation to extend lifespan, DAF-16 is required, as well as a putative nuclear hormone receptor, DAF-12. In addition, our findings suggest that signals from the somatic gonad also influence ageing, and that this effect requires DAF-2 activity. Together, our findings imply that the C. elegans insulin/IGF-1 system integrates multiple signals to define the animal's rate of ageing. This study demonstrates an inherent relationship between the reproductive state of this animal and its lifespan, and may have implications for the co-evolution of reproductive capability and longevity.

Publication types

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

MeSH terms

  • Aging / physiology
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins*
  • Forkhead Transcription Factors
  • Genes, Helminth
  • Germ Cells / physiology*
  • Gonads / cytology
  • Gonads / physiology*
  • Helminth Proteins / genetics
  • Helminth Proteins / physiology
  • Larva
  • Longevity / genetics
  • Longevity / physiology*
  • Models, Biological
  • Mutation
  • Receptor, Insulin / genetics
  • Receptor, Insulin / physiology
  • Reproduction / physiology
  • Signal Transduction*
  • Transcription Factors / genetics
  • Transcription Factors / physiology


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Helminth Proteins
  • Transcription Factors
  • daf-16 protein, C elegans
  • DAF-2 protein, C elegans
  • Receptor, Insulin