Authors: Shimokawa I; Higami Y; Utsuyama M; Tuchiya T; Komatsu T; Chiba T; Yamaza H
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.
Keywords: Animals; Animals, Genetically Modified; Antisense Elements (Genetics); Body Weight; Energy Intake; Growth Hormone/*genetics/physiology; Heterozygote; Insulin-Like Growth Factor I/*genetics/metabolism; Killer Cells, Natural/metabolism; Longevity/*genetics; Male; Phenotype; Pituitary Gland/cytology; Rats; Reverse Transcriptase Polymerase Chain Reaction; Spleen/cytology; Transgenes|
Journal: The American journal of pathology Volume: 160 Issue: 6 Pages: 2259-65 Date: June 12, 2002 PMID: 12057928 |
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. The American journal of pathology 160: 2259-65.
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