Rapamycin extends maximal lifespan in cancer-prone mice - PubMed (original) (raw)

Rapamycin extends maximal lifespan in cancer-prone mice

Vladimir N Anisimov et al. Am J Pathol. 2010 May.

Abstract

Aging is associated with obesity and cancer. Calorie restriction both slows down aging and delays cancer. Evidence has emerged that the nutrient-sensing mammalian target of rapamycin (mTOR) pathway is involved in cellular and organismal aging. Here we show that the mTOR inhibitor rapamycin prevents age-related weight gain, decreases rate of aging, increases lifespan, and suppresses carcinogenesis in transgenic HER-2/neu cancer-prone mice. Rapamycin dramatically delayed tumor onset as well as decreased the number of tumors per animal and tumor size. We suggest that, by slowing down organismal aging, rapamycin delays cancer.

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Figures

Figure 1

Figure 1

Effects of rapamycin on age-related weight gain and lifespan of female transgenic HER-2/neu mice. A: Effect of rapamycin on body weight in female transgenic HER-2/neu mice. The rapamycin group of animals received 1.5 mg/kg rapamycin three times a week for a period of 2 weeks followed by 2-week intervals without rapamycin. Mice in control group received solvent without rapamycin. Mice were weighed once a month. B: Effect of rapamycin on mice survival. Mice were observed throughout their lifespan, and all animals were autopsied. Distributions of lifespan in control and experimental groups were significantly different (log-rank test, P = 0.00588). Survival dynamics showed significant differences.

Figure 2

Figure 2

Suppression of carcinogenesis by rapamycin. A: Effect of rapamycin on tumor yield curves in female transgenic HER-2/neu mice. B: Effect of rapamycin on cumulative number of tumors in female transgenic HER-2/neu mice. C: Effect of rapamycin on distribution of mice with multiple mammary tumors in female transgenic HER-2/neu mice. Asterisks mean that according to the Fisher exact test for count data the distributions of the number of mice bearing 1 to 4, 5 to 7, and 8 to 10 tumors is significant with P = 0.0006959.

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