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

Isao Shimokawa, Yoshikazu Higami, Masanori Utsuyama, Tomoshi Tuchiya, Toshimitsu Komatsu, Takuya Chiba, Haruyoshi Yamaza

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Abstract

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.

Original languageEnglish
Pages (from-to)2259-2265
Number of pages7
JournalAmerican Journal of Pathology
Volume160
Issue number6
Publication statusPublished - 2002
Externally publishedYes

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ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Shimokawa, I., Higami, Y., Utsuyama, M., Tuchiya, T., Komatsu, T., Chiba, T., & Yamaza, H. (2002). Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model. American Journal of Pathology, 160(6), 2259-2265.