Lifespan extension and cancer prevention in HER-2/neu transgenic mice treated with low intermittent doses of rapamycin

Cancer Biology and Therapy

Volumn 15, Issue 5, 2014, Pages 586-592

  Popovich, Irina G ^a   Anisimov, Vladimir N ^a   Zabezhinski, Mark A ^a   Semenchenko, Anna V ^a   Tyndyk, Margarita L ^a   Yurova, Maria N ^a   Blagosklonny, Mikhail V ^b  

^a N N PETROV RESEARCH INSTITUTE OF ONCOLOGY   (Russian Federation)

^b ROSWELL PARK CANCER INSTITUTE   (United States)

Author keywords

Anti aging agents; Cancer; Longevity; Rapalogs

Indexed keywords

RAPAMYCIN; ANTINEOPLASTIC AGENT; EPIDERMAL GROWTH FACTOR RECEPTOR 2; ERBB2 PROTEIN, MOUSE;

ANIMAL EXPERIMENT; ARTICLE; CANCER CELL; CANCER INCIDENCE; CANCER PREVENTION; CARCINOGENESIS; CONTROLLED STUDY; DRUG DOSE REDUCTION; FEMALE; LIFE EXTENSION; LIFESPAN; MALE; MOUSE; NONHUMAN; TUMOR VOLUME; ANIMAL; DRUG EFFECTS; GENETICS; LONGEVITY; MAMMARY NEOPLASMS, ANIMAL; PATHOLOGY; PATHOPHYSIOLOGY; TRANSGENIC MOUSE;

ANIMALS; ANTICARCINOGENIC AGENTS; CARCINOGENESIS; FEMALE; LONGEVITY; MAMMARY NEOPLASMS, ANIMAL; MICE; MICE, TRANSGENIC; RECEPTOR, ERBB-2; SIROLIMUS;

EID: 84898625747     PISSN: 15384047     EISSN: 15558576     Source Type: Journal    
DOI: 10.4161/cbt.28164     Document Type: Article

References (53)

1. Blagosklonny MV. Rapalogs in cancer prevention: anti-aging or anticancer? Cancer Biol Ther 2012; 13:1349-54; PMID:23151465; http://dx.doi.org/10.4161/ cbt.22859
2. Chen C, Liu Y, Liu Y, Zheng P. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Sci Signal 2009; 2:ra75; PMID:19934433; http://dx.doi.org/10.1126/scisignal.2000559
3. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009; 460:392-5; PMID:19587680
4. Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Antoch MP, Blagosklonny MV. Rapamycin extends maximal lifespan in cancer-prone mice. Am J Pathol 2010; 176:2092-7; PMID:20363920; http://dx.doi.org/10.2353/ajpath.2010.091050
5. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, et al. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. J Gerontol A Biol Sci Med Sci 2011; 66:191-201; PMID:20974732; http://dx.doi.org/10.1093/ gerona/glq178
6. Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Rosenfeld SV, Blagosklonny MV. Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle 2011; 10:4230-6; PMID:22107964; http://dx.doi.org/10.4161/cc.10.24.18486
7. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK, et al. Rapamycin slows aging in mice. Aging Cell 2012; 11:675-82; PMID:22587563; http://dx.doi.org/10.1111/j. 1474-9726.2012.00832.x
8. Ramos FJ, Chen SC, Garelick MG, Dai DF, Liao CY, Schreiber KH, MacKay VL, An EH, Strong R, Ladiges WC, et al. Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Sci Transl Med 2012; 4:144ra103; PMID:22837538; http://dx.doi.org/10.1126/scitranslmed.3003802
9. Comas M, Toshkov I, Kuropatwinski KK, Chernova OB, Polinsky A, Blagosklonny MV, Gudkov AV, Antoch MP. New nanoformulation of rapamycin Rapatar extends lifespan in homozygous p53-/- mice by delaying carcinogenesis. Aging (Albany NY) 2012; 4:715-22; PMID:23117593
10. Komarova EA, Antoch MP, Novototskaya LR, Chernova OB, Paszkiewicz G, Leontieva OV, Blagosklonny MV, Gudkov AV. Rapamycin extends lifespan and delays tumorigenesis in heterozygous p53+/- mice. Aging (Albany NY) 2012; 4:709-14; PMID:23123616
11. Livi CB, Hardman RL, Christy BA, Dodds SG, Jones D, Williams C, Strong R, Bokov A, Javors MA, Ikeno Y, et al. Rapamycin extends life span of Rb1+/- mice by inhibiting neuroendocrine tumors. Aging (Albany NY) 2013; 5:100-10; PMID:23454836
12. Zhang Y, Bokov A, Gelfond J, Soto V, Ikeno Y, Hubbard G, Diaz V, Sloane L, Maslin K, Treaster S, et al. Rapamycin extends life and health in C57BL/6 mice. J Gerontol A Biol Sci Med Sci 2014; 69:119-30; PMID:23682161; http://dx.doi.org/10.1093/gerona/glt056
13. Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schröder S, Adler T, Afonso LC, Aguilar-Pimentel JA, Becker L, Garrett L, et al. Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest 2013; 123:3272-91; PMID:23863708; http://dx.doi.org/10.1172/JCI67674
14. Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, Uhde L, Hui J, Wall VZ, Gagnidze A, et al. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science 2013; 342:1524-8; PMID:24231806; http://dx.doi.org/10.1126/science.1244360
15. Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors MA, Li X, Nadon NL, Nelson JF, et al. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell 2013; (Forthcoming); PMID:24341993
16. Ye L, Widlund AL, Sims CA, Lamming DW, Guan Y, Davis JG, Sabatini DM, Harrison DE, Vang O, Baur JA. Rapamycin doses sufficient to extend lifespan do not compromise muscle mitochondrial content or endurance. Aging (Albany NY) 2013; 5:539-50; PMID:23929887
17. Fok WC, Chen Y, Bokov A, Zhang Y, Salmon AB, Diaz V, Javors M, Wood WH 3rd, Zhang Y, Becker KG, et al. Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome. PLoS One 2014; 9:e83988; PMID:24409289; http://dx.doi.org/10.1371/journal.pone.0083988
18. Hasty P, Livi CB, Dodds SG, Jones D, Strong R, Javors M, Fischer KE, Sloane L, Murthy K, Hubbard G, et al. eRapa Restores a Normal Life Span in a FAP Mouse Model. Cancer Prev Res (Phila) 2014; 7:169-78; PMID:24282255; http://dx.doi.org/10.1158/1940-6207.CAPR-13-0299
19. Fang Y, Bartke A. Prolonged rapamycin treatment led to beneficial metabolic switch. Aging (Albany NY) 2013; 5:328-9; PMID:23645164
20. Luo LL, Xu JJ, Fu YC. Rapamycin prolongs female reproductive lifespan. Cell Cycle 2013; 12:3353-4; PMID:24091532; http://dx.doi.org/10.4161/cc.26578
21. Mathew T, Kreis H, Friend P. Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clin Transplant 2004; 18:446-9; PMID:15233824; http://dx.doi.org/10. 1111/j.1399-0012.2004.00188.x (Pubitemid 39077081)
22. Stallone G, Schena A, Infante B, Di Paolo S, Loverre A, Maggio G, Ranieri E, Gesualdo L, Schena FP, Grandaliano G. Sirolimus for Kaposi's sarcoma in renal-transplant recipients. N Engl J Med 2005; 352:1317-23; PMID:15800227; http://dx.doi.org/10.1056/NEJMoa042831 (Pubitemid 40411498)
23. Campistol JM, Eris J, Oberbauer R, Friend P, Hutchison B, Morales JM, Claesson K, Stallone G, Russ G, Rostaing L, et al. Sirolimus therapy after early cyclosporine withdrawal reduces the risk for cancer in adult renal transplantation. J Am Soc Nephrol 2006; 17:581-9; PMID:16434506; http://dx.doi.org/10.1681/ASN.2005090993
24. Euvrard S, Morelon E, Rostaing L, Goffin E, Brocard A, Tromme I, Broeders N, del Marmol V, Chatelet V, Dompmartin A, et al.; TUMORAPA Study Group. Sirolimus and secondary skin-cancer prevention in kidney transplantation. N Engl J Med 2012; 367:329-39; PMID:22830463; http://dx.doi.org/10.1056/NEJMoa1204166
25. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 2011; 12:21-35; PMID:21157483; http://dx.doi.org/10.1038/nrm3025
26. Kaeberlein M. Longevity and aging. F1000Prime Rep 2013; 5:5; PMID:23513177; http://dx.doi.org/10.12703/P5-5
27. Kaeberlein M. mTOR Inhibition: From Aging to Autism and Beyond. Scientifica (Cairo). 2013;2013:849186.
28. Kennedy BK, Pennypacker JK. Drugs that modulate aging: the promising yet difficult path ahead. Transl Res 2013; (Forthcoming); PMID:24316383; http://dx.doi.org/10.1016/j.trsl.2013.11.007
29. Blagosklonny MV. Prevention of cancer by inhibiting aging. Cancer Biol Ther 2008; 7:1520-4; PMID:18769112; http://dx.doi.org/10.4161/cbt.7.10.6663
30. Blagosklonny MV. Rapamycin and quasi-programmed aging: four years later. Cell Cycle 2010; 9:1859-62; PMID:20436272; http://dx.doi.org/10.4161/cc.9.10. 11872
31. Blagosklonny MV. Increasing healthy lifespan by suppressing aging in our lifetime: preliminary proposal. Cell Cycle 2010; 9:4788-94; PMID:21150328; http://dx.doi.org/10.4161/cc.9.24.14360
32. Blagosklonny MV. Once again on rapamycininduced insulin resistance and longevity: despite of or owing to. Aging (Albany NY) 2012; 4:350-8; PMID:22683661
33. Blagosklonny MV. Aging, stem cells, and mammalian target of rapamycin: a prospect of pharmacologic rejuvenation of aging stem cells. Rejuvenation Res 2008; 11:801-8; PMID:18729812; http://dx.doi.org/10.1089/rej.2008.0722
34. Iglesias-Bartolome R, Patel V, Cotrim A, Leelahavanichkul K, Molinolo AA, Mitchell JB, Gutkind JS. mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis. Cell Stem Cell 2012; 11:401-14; PMID:22958932; http://dx.doi.org/10.1016/j.stem.2012.06.007
35. Iglesias-Bartolome R, Gutkind SJ. Exploiting the mTOR paradox for disease prevention. Oncotarget 2012; 3:1061-3; PMID:23165441
36. Luo Y, Li L, Zou P, Wang J, Shao L, Zhou D, Liu L. Rapamycin enhances long-term hematopoietic reconstitution of ex vivo expanded mouse hematopoietic stem cells by inhibiting senescence. Transplantation 2014; 97:20-9; PMID:24092377; http://dx.doi.org/10.1097/TP.0b013e3182a7fcf8
37. Bravo-San Pedro JM, Senovilla L. Immunostimulatory activity of lifespan-extending agents. Aging (Albany NY) 2013; 5:793-801; PMID:24389041
38. Zimmerman JJ, Kahan BD. Pharmacokinetics of sirolimus in stable renal transplant patients after multiple oral dose administration. J Clin Pharmacol 1997; 37:405-15; PMID:9156373; http://dx.doi.org/10.1002/j.1552-4604.1997. tb04318.x (Pubitemid 27215068)
39. MacDonald A, Scarola J, Burke JT, Zimmerman JJ. Clinical pharmacokinetics and therapeutic drug monitoring of sirolimus. Clin Ther 2000; 22(Suppl B):B101-21; PMID:10823378; http://dx.doi.org/10.1016/S0149-2918(00)89027-X (Pubitemid 30306050)
40. Granville CA, Warfel N, Tsurutani J, Hollander MC, Robertson M, Fox SD, Veenstra TD, Issaq HJ, Linnoila RI, Dennis PA. Identification of a highly effective rapamycin schedule that markedly reduces the size, multiplicity, and phenotypic progression of tobacco carcinogen-induced murine lung tumors. Clin Cancer Res 2007; 13:2281-9; PMID:17404113; http://dx.doi.org/10.1158/1078-0432. CCR-06-2570 (Pubitemid 46649898)
41. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Kovalenko IG, Poroshina TE, Semenchenko AV, Provinciali M, et al. Effect of metformin on life span and on the development of spontaneous mammary tumors in HER-2/ neu transgenic mice. Exp Gerontol 2005; 40:685-93; PMID:16125352; http://dx.doi.org/10.1016/j.exger.2005.07.007 (Pubitemid 41265819)
42. Anisimov VN, Egormin PA, Bershtein LM, Zabezhinskii MA, Piskunova TS, Popovich IG, Semenchenko AV. Metformin decelerates aging and development of mammary tumors in HER-2/neu transgenic mice. Bull Exp Biol Med 2005; 139:721-3; PMID:16224592; http://dx.doi.org/10.1007/s10517-005-0389-9 (Pubitemid 41372239)
43. Anisimov VN, Berstein LM, Egormin PA, Piskunova TS, Popovich IG, Zabezhinski MA, Tyndyk ML, Yurova MV, Kovalenko IG, Poroshina TE, et al. Metformin slows down aging and extends life span of female SHR mice. Cell Cycle 2008; 7:2769-73; PMID:18728386; http://dx.doi.org/10.4161/cc.7.17.6625
44. Anisimov VN. Metformin for aging and cancer prevention. Aging (Albany NY) 2010; 2:760-74; PMID:21084729
45. Anisimov VN, Berstein LM, Popovich IG, Zabezhinski MA, Egormin PA, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Kovalenko IG, et al. If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging (Albany NY) 2011; 3:148-57; PMID:21386129
46. Anisimov VN. Metformin: do we finally have an anti-aging drug? Cell Cycle 2013; 12:3483-9; PMID:24189526; http://dx.doi.org/10.4161/cc.26928
47. Moiseeva O, Deschênes-Simard X, Pollak M, Ferbeyre G. Metformin, aging and cancer. Aging (Albany NY) 2013; 5:330-1; PMID:23660016
48. Martin-Montalvo A, Mercken EM, Mitchell SJ, Palacios HH, Mote PL, Scheibye-Knudsen M, Gomes AP, Ward TM, Minor RK, Blouin MJ, et al. Metformin improves healthspan and lifespan in mice. Nat Commun 2013; 4:2192; PMID:23900241; http://dx.doi.org/10.1038/ncomms3192
49. Anisimov VN. Metformin and rapamycin are masterkeys for understanding the relationship between cell senescent, aging and cancer. Aging (Albany NY) 2013; 5:337-8; PMID:23715473
50. Leontieva OV, Paszkiewicz GM, Blagosklonny MV. Mechanistic or mammalian target of rapamycin (mTOR) may determine robustness in young male mice at the cost of accelerated aging. Aging (Albany NY) 2012; 4:899-916; PMID:23443503
51. Anisimov VN, Popovich IG, Zabezhinski MA. Methods of testing pharmacological drugs effects on aging and life span in mice. Methods Mol Biol 2013; 1048:145-60; PMID:23929104; http://dx.doi.org/10.1007/978-1-62703-556-9-12
52. Wu JJ, Liu J, Chen EB, Wang JJ, Cao L, Narayan N, Fergusson MM, Rovira II, Allen M, Springer DA, et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep 2013; 4:913-20; PMID:23994476; http://dx.doi.org/10.1016/j.celrep. 2013.07.030
53. Khapre RV, Kondratova AA, Patel S, Dubrovsky Y, Wrobel M, Antoch MP, Kondratov RV. MAL1- dependent regulation of the mTOR signaling pathway delays aging. Aging (Albany, NY Online) 2014; 6: In press.