Identification of a DAF-16 transcriptional target gene, scl-1, that regulates longevity and stress resistance in Caenorhabditis elegans

Curr Biol. 2003 Mar 4;13(5):427-31. doi: 10.1016/s0960-9822(03)00108-8.


In Caenorhabditis elegans, an insulin-like signaling pathway, which includes the daf-2 and age-1 genes, controls longevity and stress resistance. Downregulation of this pathway activates the forkhead transcription factor DAF-16, whose transcriptional targets are suggested to play an essential role in controlling the phenotypes governed by this pathway. We have surveyed the genes that have the DAF-16 consensus binding element (DBE) within putative regulatory regions. Here, we show that one such gene, termed scl-1, is a positive regulator of longevity and stress resistance. Expression of scl-1 is upregulated in long-lived daf-2 and age-1 mutants and is undetectable in a short-lived daf-16 mutant. SCL-1 is a putative secretory protein with an SCP domain and is homologous to the mammalian cysteine-rich secretory protein (CRISP) family. scl-1 is required for the extension of the life span of daf-2 and age-1 mutants, and downregulation of scl-1 reduces both life span and stress resistance of this animal. SCL-1, whose expression is dependent on DAF-16, is the first example of a putative secretory protein that positively regulates longevity and stress resistance.

Publication types

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

MeSH terms

  • Aging / genetics*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Caenorhabditis elegans / genetics*
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism
  • Forkhead Transcription Factors
  • Longevity / genetics*
  • Molecular Sequence Data
  • Transcription Factors / metabolism*


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • SCL-1 protein, C elegans
  • Transcription Factors
  • daf-16 protein, C elegans