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

*この研究の対応する著者

研究成果: Article査読

96 被引用数 (Scopus)

抄録

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.

本文言語English
ページ(範囲)2259-2265
ページ数7
ジャーナルAmerican Journal of Pathology
160
6
DOI
出版ステータスPublished - 2002 6月
外部発表はい

ASJC Scopus subject areas

  • 病理学および法医学

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