Tissue-specific activities of C. elegans DAF-16 in the regulation of lifespan

Cell. 2003 Nov 14;115(4):489-502. doi: 10.1016/s0092-8674(03)00889-4.


In C. elegans, the transcription factor DAF-16 promotes longevity in response to reduced insulin/IGF-1 signaling or germline ablation. In this study, we have asked how different tissues interact to specify the lifespan of the animal. We find that several tissues act as signaling centers. In particular, DAF-16 activity in the intestine, which is also the animal's adipose tissue, completely restores the longevity of daf-16(-) germline-deficient animals, and increases the lifespans of daf-16(-) insulin/IGF-1-pathway mutants substantially. Our findings indicate that DAF-16 may control two types of downstream signals: DAF-16 activity in signaling cells upregulates DAF-16 in specific responding tissues, possibly via regulation of insulin-like peptides, and also evokes DAF-16-independent responses. We suggest that this network of tissue interactions and feedback regulation allows the tissues to equilibrate and fine-tune their expression of downstream genes, which, in turn, coordinates their rates of aging within the animal.

Publication types

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

MeSH terms

  • Adipose Tissue / metabolism
  • Aging / drug effects
  • Aging / physiology
  • Animals
  • Animals, Genetically Modified
  • Caenorhabditis elegans / cytology
  • Caenorhabditis elegans / drug effects
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Forkhead Transcription Factors
  • Gene Deletion
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental
  • Germ-Line Mutation / genetics
  • Insulin / pharmacology
  • Insulin-Like Growth Factor I / pharmacology
  • Intestinal Mucosa / metabolism*
  • Longevity / drug effects
  • Longevity / physiology*
  • Mosaicism
  • Organ Specificity
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptor, Insulin / metabolism
  • Signal Transduction / drug effects
  • Stress, Physiological / genetics
  • Stress, Physiological / physiopathology
  • Transcription Factors / genetics*
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • RNA, Messenger
  • Transcription Factors
  • daf-16 protein, C elegans
  • Insulin-Like Growth Factor I
  • DAF-2 protein, C elegans
  • Receptor, Insulin