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Blood samples were drawn from the tail vein without anesthesia between 9:00 and 12:00 after overnight fasting. "Young" represents the age between 6 and 8 months; "Old" represents the age between 24 and 25 months. Data represent means ± SD of 4 to 7 rats. 3-f ANOVA analyzed the main effects of rat group, diet, and age.

Immunological analysis of transgenic rats demonstrated that the proportion and activity of NK cells in splenocytes were reduced significantly in (tg/tg) rats compared with (—/—) and (tg/—) rats (Shimokawa et al., 2002). NK cells are known to protect animals from neoplastic processes (Lotzova, 1993); thus in Wistar rats, severe suppression of the GH-IGF-1 axis might promote neoplastic processes due to dysfunction of the immune system, because GH and IGF-1 are required for normal development of the immune system (Dorshkind and Horseman, 2000). In this regard, however, it is intriguing that Snell mice, which show the same phenotypes as Ames mice, including a lengthened lifespan, achieve normal immune responsiveness even if GH is almost deficient (Cross et al., 1992).

Glucose, Insulin and Related Parameters

A distinctive feature of long-lived mice, in which the somatotropic axis is suppressed, is a reduced serum insulin concentration (Hsieh et al., 2002; Shimokawa et al., 2003). As noted above, diminished insulin-like signaling by reduction-of-function mutations favors longevity in invertebrates, in which insulin and IGF-1 signal pathways are not clearly separated. Similar manipulations of insulin signal genes in mammals, however, resulted in metabolic disorders and shortened lifespans; there was only one exception, a strain of mice whose insulin receptor gene was disrupted exclusively in white fat tissues (Bluher et al., 2003).

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