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Lifespan extension by reduction of the growth hormone‐insulin‐like growth factor‐1 axis: relation to caloric restriction
Author(s) -
Shimokawa Isao,
Higami Yoshikazu,
Tsuchiya Tomoshi,
Otani Hiroshi,
Komatsu Toshimitsu,
Chiba Takuya,
Yamaza Haruyoshi
Publication year - 2003
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.02-0819fje
Subject(s) - endocrinology , medicine , transgene , growth factor , insulin like growth factor , caloric theory , genetically modified mouse , growth hormone , longevity , biology , phenotype , hormone , genetics , receptor , gene
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.