Authors: Shimokawa I; Higami Y; Tsuchiya T; Otani H; Komatsu T; Chiba T; Yamaza H
Abstract: A reduced growth hormone (GH)-insulin-like growth factor (IGF)-1 axis is associated with an extension of lifespan in laboratory rodents. Several phenotypes of such animal models resemble those induced by caloric restriction (CR). Using a transgenic male Wistar rat model whose GH-IGF-1 axis was moderately suppressed by overexpression of the antisense GH transgene (tg), we elucidated a relationship between the effects of a reduced GH-IGF-1 axis and CR for some biomarkers of aging, lifespan, and pathologies. Heterozygous (tg/-) rats fed ad libitum (AL) had a dwarf phenotype similar to that of control nontransgenic (-/-) rats subjected to 30% CR from 6 wk of age. Both the reduced GH-IGF-1 axis and CR extended lifespan to a similar extent, although the effect of CR seemed to be greater. There was an additive effect of CR to lifespan extension when tg/- rats were subjected to CR. Pathologic analyses indicated that the preventive effect of CR on selected diseases was greater than that of the reduced GH-IGF-1 axis. The present study suggests that CR affects aging and longevity by mechanisms other than suppression of the GH-IGF-1 axis, although CR might exhibit its effects partly through the reduced GH-IGF-1 axis.
Keywords: Adenoma/prevention & control; Animals; Animals, Genetically Modified; *Caloric Restriction; Coronary Thrombosis/prevention & control; Disease; Growth Hormone/*genetics; Heterozygote; Insulin-Like Growth Factor I/*analysis; Kidney Diseases/prevention & control; *Longevity; Male; Models, Biological; Phenotype; Pituitary Neoplasms/prevention & control; Rats; Rats, Wistar|
Journal: FASEB journal : official publication of the Federation of American Societies for Experimental Biology Volume: 17 Issue: 9 Pages: 1108-9 Date: April 15, 2003 PMID: 12692087 |
Shimokawa I, Higami Y, Tsuchiya T, Otani H, Komatsu T, Chiba T, Yamaza H (2003) Life span extension by reduction of the growth hormone-insulin-like growth factor-1 axis: relation to caloric restriction. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 17: 1108-9.
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