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FASEB J. 2003 Jun;17(9):1108-9. Epub 2003 Apr 8.

Life span extension by reduction of the growth hormone-insulin-like growth factor-1 axis: relation to caloric restriction.

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1
Department of Pathology & Gerontology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki City 852-8523, Japan. shimo@net.nagasaki-u.ac.jp

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.

PMID:
12692087
DOI:
10.1096/fj.02-0819fje
[Indexed for MEDLINE]
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