Rapamycin and P53 are additive in life extension

P53 modifies the effectiveness of Rapamycin in mice. P53-/- mice had no life extension benefit from Rapa while other P53 mice had life extension similar to ITP results.

Of note:
Most mice seem to die of lymphoma.

p53 genotype influenced rapamycin-mediated life span extension. eRapa did not significantly benefit p53-/- mice (Figure 1), which had median survival times (male + female) of 198.5 and 192 days for control- and eRapa-fed mice, respectively (p=0.2410). By contrast, eRapa extended the median survival of p53+/- (520 to 582 days, p=0.0522) and p53+/+ mice (681 to 802.5 days, p=0.0013). eRapa improved median survival more for p53+/- females compared to p53+/- males (15.5% vs. 13.7% increase) and more for p53+/+ females compared to p53+/+ males (20.9% vs. 11.6% increase), similar to previous reports [4, 35]. The p53 gene dose appears to directly correlate with rapamycin’s effectiveness at extending mouse life span.

Chronic eRapa treatment did not significantly change tumor incidence in p53-deficient mice. Necropsies were performed on moribund mice after sacrifice or soon after natural death. Potential tumor masses and abnormal tissues were analyzed. Cancer, mostly lymphoma, was the major pathology identified at the time of death for all genotypes (Table 1). With control chow, p53-/- mice had a higher lymphoma incidence than p53+/- or p53+/+ mice (70% vs. 59% and 53%, respectively). With eRapa chow, there was a lower trend in the incidence of lymphoma in p53-/- mice but corresponding higher trend in the incidence of sarcomas (including leiomyoma, rhabdomyosarcoma, hemangiosarcoma and osteosarcoma); there was a similar but less pronounced trend in p53+/- mice. Very little change was observed in wild type p53+/+ mice, similar to a report that showed eRapa had only a minor effect on tumor multiplicity or burden in genetically heterogenous mice [35].

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Many natural products have been reported to target the p53-MDM2 pathway, including chalcones, genistein, curcumin, sesquiterpenoids, ginsenosides, etc.;

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P53 enhancing agents should be looked at for synergistic benefits with Rapamycin in terms of cancer suppression and life extension.

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Full table also includes berberine and melatonin.

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Restoring mutant P53 due to human papilloma virus (HPV) would also be of high value in preventing cervical pre-cancer / cancer as well. @DeStrider Nice thread since P53 is one of our vital protection mechanisms against cancer.

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Very nice find.
My take is that under a normal and fully functional P53 condition, rapamycin is additive and protective even at low doses.
Under mutated and dysfunctional P53 status, as seen in cancer, low dose rapamycin isn’t protective, but very high blood levels could still be useful as more of a potential curative but not preventative.

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one cannot simply take anything to restore p53 or can you ?

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