Rapamycin extends life span of Rb1 +/− mice by inhibiting neuroendocrine tumors

摘要: Chronic treatment of mice with an enterically released formulation rapamycin (eRapa) extends median and maximum life span, partly by attenuating cancer. The mechanistic basis this response is not known. To gain a better understanding these in vivo effects, we used defined preclinical model neuroendocrine cancer, Rb1+/− mice. Previous results showed that diet restriction (DR) had minimal or no effect on the lifespan mice, suggesting beneficial to DR dependent pRb1. Since long-term eRapa may at least partially mimic chronic extension, predicted it would have Beginning 9 weeks age until death, fed without 14 mg/kg food, which approximate dose 2.24 body weight per day, yielded blood levels about 4 ng/ml. Surprisingly, found dramatically extended span both female male slowed appearance growth pituitary decreased incidence thyroid tumors commonly observed In model, appears act differently than DR, diverse mechanisms action survival anti-tumor effects. particular effects did depend Rb1.