Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model.
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.
Shimokawa
Isao
I
Department of Respiratory and Digestive Medicine, Division of Experimental Medicine, Pathology, and Gerontology, Nagasaki University School of Medicine, Nagasaki City, Japan. shimo@net.nagasaki-u.ac.jp
Higami
Yoshikazu
Y
Utsuyama
Masanori
M
Tuchiya
Tomoshi
T
Komatsu
Toshimitsu
T
Chiba
Takuya
T
Yamaza
Haruyoshi
H
D000818:Animals; D030801:Animals, Genetically Modified; D016375:Antisense Elements (Genetics); D001835:Body Weight; D002149:Energy Intake; D013006:Growth Hormone / Q000235:genetics* / Q000502:physiology; D006579:Heterozygote; D007334:Insulin-Like Growth Factor I / Q000235:genetics* / Q000378:metabolism; D007694:Killer Cells, Natural / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D010641:Phenotype; D010902:Pituitary Gland / Q000166:cytology; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013154:Spleen / Q000166:cytology; D019076:Transgenes
D016375:Antisense Elements (Genetics); D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone