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Data represent the number of rats. The proportion of each category or disease was analyzed by x2 test or Fisher exact test. ap < 0.05 and cp < 0.10 versus -/- (AL) rats. b,dp < 0.05 versus tg/- (AL) rats.

Data represent the number of rats. The proportion of each category or disease was analyzed by x2 test or Fisher exact test. ap < 0.05 and cp < 0.10 versus -/- (AL) rats. b,dp < 0.05 versus tg/- (AL) rats.

that suffered from cardiac thrombi was limited, the prevalence was reduced in (tg/tg) rats; this was also seen in CR rats.

Probable causes of death differed among the three rat groups (Table 31.4). The (tg/tg) rats died mostly of neoplastic diseases, particularly leukemia, which was never observed in (—/—) rats. To assess the contribution of neoplastic causes of death to the shortened lifespan of (tg/tg) rats, conditional survival curves for neoplastic causes of death were generated (Figure 31.2).

In this analysis, nonneoplastic causes of death were considered to be the same censorship as random sacrifice of rats (see Shimokawa et al., 1991 for details). Analysis confirmed that (tg/tg)-AL rats died earlier than other rats from neoplasms. The survival curve of (tg/—)-AL rats did not differ from that of (—/—)-AL rats, suggesting that the increased survival of (tg/—) rats is mostly due to delayed nonneoplastic causes of death. The proportion of pituitary adenoma as the cause of death increased in (tg/—)-AL rats compared with (—/—) rats, although the prevalence of pituitary adenoma was similar between the two groups. It is possible therefore that, in (tg/—)-AL rats, the reduced incidence of lethal nonneoplastic disorders contributes to lifespan extension, and thus, pituitary adenoma as a cause of death increased even though the onset and progression of pituitary tumors was not affected. In contrast, CR significantly decreased the prevalence of pituitary adenoma and the proportion of related deaths, suggesting that CR suppresses pituitary tumorigenesis. CR seemed to delay the occurrence of neoplastic causes (data not shown) as well as non-neoplastic causes of death in (—/—) and (tg/—) rats as

0 48 96 144

Age (weeks)

Figure 31.2. Conditional survival curves of the neoplastic causes of death. Non-neoplastic deaths were considered to be the same censorship as random sacrifice of rats. Survival curves were produced using Kaplan-Meier product limit estimates and compared using the log rank test (Shimokawa et al., 1991).

0 48 96 144

Age (weeks)

Figure 31.2. Conditional survival curves of the neoplastic causes of death. Non-neoplastic deaths were considered to be the same censorship as random sacrifice of rats. Survival curves were produced using Kaplan-Meier product limit estimates and compared using the log rank test (Shimokawa et al., 1991).

seen in the inhibited prevalence of cardiac thrombi and proportion of related deaths.

At present, pathologic analyses of long-lived mice are limited; however, it has been reported that the occurrence of neoplastic causes of death is delayed in Ames mice (Ikeno et al., 2003). Because GH and IGF-1 are anabolic hormones that might increase the risk of several cancers (Ibrahim and Yee, 2004), the reduced GH-IGF-1 axis was expected to reduce the occurrence or progression of neoplastic diseases, thus delaying neoplastic causes of death.

Blood Pressure Health

Blood Pressure Health

Your heart pumps blood throughout your body using a network of tubing called arteries and capillaries which return the blood back to your heart via your veins. Blood pressure is the force of the blood pushing against the walls of your arteries as your heart beats.Learn more...

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