TY - JOUR
T1 - Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model
AU - Shimokawa, Isao
AU - Higami, Yoshikazu
AU - Utsuyama, Masanori
AU - Tuchiya, Tomoshi
AU - Komatsu, Toshimitsu
AU - Chiba, Takuya
AU - Yamaza, Haruyoshi
N1 - Funding Information:
Supported in part by the Research Grant for Longevity Sciences ( grant 11-C ) from the Ministry of Health, Welfare, and Labor of Japan.
PY - 2002/6
Y1 - 2002/6
N2 - 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.
AB - 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.
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U2 - 10.1016/S0002-9440(10)61173-X
DO - 10.1016/S0002-9440(10)61173-X
M3 - Article
C2 - 12057928
AN - SCOPUS:0036086818
SN - 0002-9440
VL - 160
SP - 2259
EP - 2265
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 6
ER -