Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model - PubMed (original) (raw)

Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model

Isao Shimokawa et al. Am J Pathol. 2002 Jun.

Abstract

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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Figures

Figure 1.

Figure 1.

Transgene expression detected by RT-PCR in the pituitary gland, spleen, and thymus at 6 months of age.

Figure 2.

Figure 2.

Immunohistochemistry for GH in the pituitary gland at 6 months of age: a, tg/tg; b, tg/−; c, −/−. Scale bar, 100 μm (c).

Figure 3.

Figure 3.

Food intake (g/rat/day) in rat groups in the longevity study. The points represent the mean ± SD (n = 10). Data of 12-week intervals are shown, and are not depicted when the number of rats was below five.

Figure 4.

Figure 4.

Body weight in rat groups of the longevity study. The points represent the mean ± SD; n = 30 for each group at the start of the study decreased with age. Data are not depicted when the number of rats was below five.

Figure 5.

Figure 5.

Food intake/100 g body weight (FI/100gBW) in rat groups of the longevity study. The points represent the mean ± SD (n = 10). Data of 12-week intervals are shown, and are not depicted when the number of rats was below five.

Figure 6.

Figure 6.

Group survival curves (n = 30 at the start of the study).

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