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

被引：85
|
作者：
Shimokawa, I
Higami, Y
Utsuyama, M
Tuchiya, T
Komatsu, T
Chiba, T
Yamaza, H
机构：
[1] Nagasaki Univ, Sch Med, Dept Resp & Digest Med, Div Expt Med Pathol & Gerontol, Nagasaki 8528523, Japan
[2] Tokyo Med & Dent Univ, Grad Sch, Dept Pathol & Immunol, Tokyo, Japan
来源：
AMERICAN JOURNAL OF PATHOLOGY | 2002年 / 160卷 / 06期
关键词：
D O I：
10.1016/S0002-9440(10)61173-X
中图分类号：
R36 [病理学];
学科分类号：
100104 ;
摘要：
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.
引用
收藏
页码：2259 / 2265
页数：7
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