Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model

Am J Pathol. 2002 Jun;160(6):2259-65. doi: 10.1016/S0002-9440(10)61173-X.


The longer life span in dwarf mice suggests that a reduction in the growth hormone (GH)-insulin-like growth factor (IGF)-1 axis retards aging and extends the life span in mammals. We tested this hypothesis in a transgenic strain of rats whose GH gene was suppressed by an anti-sense GH transgene. Male rats homozygous for the transgene (tg/tg) had a reduced number of pituitary GH cells, a lower plasma concentration of IGF-1, and a dwarf phenotype. Heterozygous rats (tg/-) had an intermediate phenotype in plasma IGF-1, food intake, and body weight between tg/tg and control (-/-) rats. The life span of tg/tg rats was 5 to 10% shorter than -/- rats. In contrast, the life span of tg/- rats was 7 to 10% longer than -/- rats. Pathological analysis suggested that neoplasms caused earlier death in tg/tg rats; in contrast, tg/- rats had reduced nonneoplastic diseases and a prolonged life span. Immunological analysis revealed a smaller population and lower activity of splenic natural killer cells in tg/tg rats. The results of the present study support the hypothesis, but suggest that there is an optimal level of the GH-IGF-1 axis to maximize survival in mammals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antisense Elements (Genetics)
  • Body Weight
  • Energy Intake
  • Growth Hormone / genetics*
  • Growth Hormone / physiology
  • Heterozygote
  • Insulin-Like Growth Factor I / genetics*
  • Insulin-Like Growth Factor I / metabolism
  • Killer Cells, Natural / metabolism
  • Longevity / genetics*
  • Male
  • Phenotype
  • Pituitary Gland / cytology
  • Rats
  • Reverse Transcriptase Polymerase Chain Reaction
  • Spleen / cytology
  • Transgenes


  • Antisense Elements (Genetics)
  • Insulin-Like Growth Factor I
  • Growth Hormone