The endocrine regulation of aging by insulin-like signals

Science. 2003 Feb 28;299(5611):1346-51. doi: 10.1126/science.1081447.


Reduced signaling of insulin-like peptides increases the life-span of nematodes, flies, and rodents. In the nematode and the fly, secondary hormones downstream of insulin-like signaling appear to regulate aging. In mammals, the order in which the hormones act is unresolved because insulin, insulin-like growth factor-1, growth hormone, and thyroid hormones are interdependent. In all species examined to date, endocrine manipulations can slow aging without concurrent costs in reproduction, but with inevitable increases in stress resistance. Despite the similarities among mammals and invertebrates in insulin-like peptides and their signal cascade, more research is needed to determine whether these signals control aging in the same way in all the species by the same mechanism.

Publication types

  • Review

MeSH terms

  • Aging*
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology
  • Caenorhabditis elegans Proteins*
  • Caloric Restriction
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology
  • Endocrine System / physiology*
  • Forkhead Transcription Factors
  • Gene Expression Regulation
  • Growth Hormone / metabolism
  • Humans
  • Insect Hormones / physiology
  • Insulin / metabolism*
  • Longevity*
  • Mice
  • Signal Transduction*
  • Somatomedins / metabolism*
  • Transcription Factors / genetics
  • Transcription Factors / metabolism


  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insect Hormones
  • Insulin
  • Somatomedins
  • Transcription Factors
  • daf-16 protein, C elegans
  • Growth Hormone