2012
DOI: 10.18632/aging.100498
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Abstract: The TOR (Target of Rapamycin) pathway accelerates cellular and organismal aging. Similar to rapamycin, p53 can inhibit the mTOR pathway in some mammalian cells. Mice lacking one copy of p53 (p53+/− mice) have an increased cancer incidence and a shorter lifespan. We hypothesize that rapamycin can delay cancer in heterozygous p53+/− mice. Here we show that rapamycin (given in a drinking water) extended the mean lifespan of p53+/− mice by 10% and when treatment started early in life (at the age less than 5 months… Show more

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Cited by 124 publications
(90 citation statements)
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References 42 publications
(49 reference statements)
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“…87 Similarly, rapamycin delayed cancer in p53 +/− and p53 −/− mice. 63,64 Noteworthy, the effect of rapamycin was blunted when it was used later in life, consistent with its indirect anti-cancer effect. 63 In conclusion, mice lacking p53 is characterized by oncophilic metabolism, an additional factor fostering carcinogenesis.…”
Section: Discussionmentioning
confidence: 84%
“…[60][61][62] Rapamycin extends lifespan and delays cancer in p53 +/− and p53 −/− mice. [63][64][65] In p53 −/− mice both direct (anti-cancer) and indirect (anti-aging) models identically predict that rapamycin will delay cancer and extend life span. There is a hint for indirect effects: rapamycin is more effective when given early in life.…”
Section: Introductionmentioning
confidence: 99%
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“…56,57 The regulation of cell death by the p53 protein is quite complex, acting both at the level of autophagy, 58 lysosomes, 59 or at the core machinery of programmed cell death. [60][61][62][63][64][65] In addition to DNA damage response and cell death, p53 plays a crucial role in regulating cellular senescence [66][67][68] by interacting, for example, with MageA2, 69 PATZ1, 70 4E-BP1, 71 mTOR, 72,73 highlighting the vast complexity of this crucial regulation.…”
Section: Introductionmentioning
confidence: 99%
“…[2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] Furthermore, rapamycin delays the onset of cancer in mice. [3][4][5][6][7][9][10][11][12][13]15,18 Rapamycin and everolimus (a rapamycin analog) decrease the risk of cancer in humans, who receive these rapalogs to prevent transplant rejection. 1,[21][22][23][24] Therefore, rapalogs such as rapamycin are considered for both prevention of cancer and extension of healthy life span in humans.…”
Section: Introductionmentioning
confidence: 99%