Life span extension by reduction of the growth hormone-insulin-like growth factor-1 axis: relation to caloric restriction.
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.
Shimokawa
Isao
I
Department of Pathology & Gerontology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City 852-8523, Japan. shimo@net.nagasaki-u.ac.jp
Higami
Yoshikazu
Y
Tsuchiya
Tomoshi
T
Otani
Hiroshi
H
Komatsu
Toshimitsu
T
Chiba
Takuya
T
Yamaza
Haruyoshi
H
D000236:Adenoma / Q000517:prevention & control; D000818:Animals; D030801:Animals, Genetically Modified; D031204:Caloric Restriction; D003328:Coronary Thrombosis / Q000517:prevention & control; D004194:Disease; D013006:Growth Hormone / Q000235:genetics*; D006579:Heterozygote; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D007674:Kidney Diseases / Q000517:prevention & control; D008136:Longevity; D008297:Male; D008954:Models, Biological; D010641:Phenotype; D010911:Pituitary Neoplasms / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar
D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone