Intermittent administration of rapamycin extends the life span of female C57BL/6J Mice

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 71, Issue 7, 2016, Pages 876-881

  Apelo, Sebastian I Arriola ^a,b   Pumper, Cassidy P ^a,b   Baar, Emma L ^a,b   Cummings, Nicole E ^a,b,c   Lamming, Dudley W ^a,b,c  

^a UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^b WILLIAM S MIDDLETON MEMORIAL VETERANS HOSPITAL   (United States)

^c UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

Anti aging; Life span; Mice; mTOR; Rapamycin

Indexed keywords

IMMUNOSUPPRESSIVE AGENT; RAPAMYCIN; TARGET OF RAPAMYCIN KINASE;

AGING; ANIMAL; C57BL MOUSE; CHRONOPHARMACOLOGY; DRUG ADMINISTRATION; DRUG EFFECTS; FEMALE; GLUCOSE METABOLISM DISORDERS; IMMUNE SYSTEM; LONGEVITY; METABOLISM; MOUSE; PHYSIOLOGY; SIGNAL TRANSDUCTION; TREATMENT OUTCOME;

AGING; ANIMALS; DRUG ADMINISTRATION SCHEDULE; DRUG CHRONOTHERAPY; FEMALE; GLUCOSE METABOLISM DISORDERS; IMMUNE SYSTEM; IMMUNOSUPPRESSIVE AGENTS; LONGEVITY; MICE; MICE, INBRED C57BL; SIGNAL TRANSDUCTION; SIROLIMUS; TOR SERINE-THREONINE KINASES; TREATMENT OUTCOME;

EID: 84979255623     PISSN: 10795006     EISSN: 1758535X     Source Type: Journal    
DOI: 10.1093/gerona/glw064     Document Type: Article

References (44)

1. Zhang Y, Bokov A, Gelfond J, et al. Rapamycin extends life and health in C57BL/6 mice. J Gerontol A Biol Sci Med Sci. 2014;69:119-130. doi: 10.1093/gerona/glt056
2. Harrison DE, Strong R, Sharp ZD, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392-395. doi: 10.1038/nature08221
3. Majumder S, Caccamo A, Medina DX, et al. Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL- 1beta and enhancing NMDA signaling. Aging Cell. 2012;11:326-335. doi: 10.1111/j.1474-9726.2011.00791.x
4. Spilman P, Podlutskaya N, Hart MJ, et al. Inhibition of mTOR by rapamycin abolishes cognitive deficits and reduces amyloid-beta levels in a mouse model of Alzheimer's disease. PLoS One. 2010;5:e9979. doi: 10.1371/journal.pone.0009979
5. Dai DF, Karunadharma PP, Chiao YA, et al. Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell. 2014;13:529-539. doi: 10.1111/acel.12203
6. Ozcelik S, Fraser G, Castets P, et al. Rapamycin attenuates the progression of tau pathology in P301S tau transgenic mice. PLoS One. 2013;8:e62459. doi: 10.1371/journal.pone.0062459
7. Wilkinson JE, Burmeister L, Brooks SV, et al. Rapamycin slows aging in mice. Aging Cell. 2012;11:675-682. doi: 10.1111/j.1474-9726.2012.00832.x
8. Lin AL, Jahrling JB, Zhang W, et al. Rapamycin rescues vascular, metabolic and learning deficits in apolipoprotein E4 transgenic mice with pre-symptomatic Alzheimer's disease. J Cereb Blood Flow Metab. 2015. doi: 10.1177/0271678X15621575
9. Halloran J, Hussong SA, Burbank R, et al. Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and noncognitive components of behavior throughout lifespan in mice. Neuroscience. 2012;223:102-113. doi: 10.1016/j.neuroscience.2012.06.054
10. Lin AL, Zheng W, Halloran JJ, et al. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer's disease. J Cereb Blood Flow Metab. 2013;33:1412-1421. doi: 10.1038/jcbfm.2013.82
11. Ramos FJ, Chen SC, Garelick MG, 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. doi: 10.1126/scitranslmed.3003802
12. Lamming DW, Ye L, Sabatini DM, Baur JA. Rapalogs and mTOR inhibitors as anti-aging therapeutics. J Clin Invest. 2013;123:980-989. doi: 10.1172/JCI64099
13. Trelinska J, Dachowska I, Kotulska K, Fendler W, Jozwiak S, Mlynarski W. Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening. Anticancer Drugs. 2015;26:437-442. doi: 10.1097/CAD.0000000000000207
14. Lamming DW. Inhibition of the mechanistic target of rapamycin (mTOR) - rapamycin and beyond. In: Olshansky SJ, Martin GM, Kirkland JL, eds. Aging: The Longevity Dividend. Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press; 2016:165-178. doi: 10.1101/cshperspect.a025924
15. Anisimov VN, Zabezhinski MA, Popovich IG, et al. Rapamycin extends maximal lifespan in cancer-prone mice. Am J Pathol. 2010;176:2092-2097. doi: 10.2353/ajpath.2010.091050
16. Anisimov VN, Zabezhinski MA, Popovich IG, et al. Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle. 2011;10:4230-4236. doi: 10.4161/cc.10.24.18486
17. Liu Y, Diaz V, Fernandez E, et al. Rapamycin-induced metabolic defects are reversible in both lean and obese mice. Aging. 2014;6:742-754.
18. Yang SB, Lee HY, Young DM, et al. Rapamycin induces glucose intolerance in mice by reducing islet mass, insulin content, and insulin sensitivity. J Mol Med. 2012;90:575-585. doi: 10.1007/s00109-011-0834-3
19. Lamming DW, Ye L, Astle CM, Baur JA, Sabatini DM, Harrison DE. Young and old genetically heterogeneous HET3 mice on a rapamycin diet are glucose intolerant but insulin sensitive. Aging Cell. 2013;12:712-718. doi: 10.1111/acel.12097
20. Lamming DW, Ye L, Katajisto P, et al. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. 2012;335:1638-1643. doi: 10.1126/science.1215135
21. Sataranatarajan K, Ikeno Y, Bokov A, et al. Rapamycin increases mortality in db/db mice, a mouse model of type 2 diabetes. J Gerontol A Biol Sci Med Sci. 2015. doi: 10.1093/gerona/glv170
22. Delgoffe GM, Pollizzi KN, Waickman AT, et al. The kinase mTOR regulates the differentiation of helper T cells through the selective activation of signaling by mTORC1 and mTORC2. Nature Immunol. 2011;12:295-303. doi: 10.1038/ni.2005
23. Festuccia WT, Pouliot P, Bakan I, Sabatini DM, Laplante M. Myeloidspecific Rictor deletion induces M1 macrophage polarization and potentiates in vivo pro-inflammatory response to lipopolysaccharide. PLoS One. 2014;9:e95432. doi: 10.1371/journal.pone.0095432
24. Schreiber KH, Ortiz D, Academia EC, Anies AC, Liao CY, Kennedy BK. Rapamycin-mediated mTORC2 inhibition is determined by the relative expression of FK506-binding proteins. Aging Cell. 2015;14:265-273. doi: 10.1111/acel.12313
25. Ye L, Varamini B, Lamming DW, Sabatini DM, Baur JA. Rapamycin has a biphasic effect on insulin sensitivity in C2C12 myotubes due to sequential disruption of mTORC1 and mTORC2. Front Genet. 2012;3:177. doi: 10.3389/fgene.2012.00177
26. Lamming DW, Mihaylova MM, Katajisto P, et al. Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan. Aging Cell. 2014;13:911-917. doi: 10.1111/acel.12256
27. Sarbassov DD, Ali SM, Sengupta S, et al. Prolonged rapamycin treatment inhibits mTORC2 assembly and Akt/PKB. Mol Cell. 2006;22:159-168. doi: 10.1016/j.molcel.2006.03.029
28. Arriola Apelo SI, Neuman JC, Baar EL, et al. Alternative rapamycin treatment regimens mitigate the impact of rapamycin on glucose homeostasis and the immune system. Aging Cell. 2016;15:28-38. doi: 10.1111/acel.12405
29. Wang C, Li Q, Redden DT, Weindruch R, Allison DB. Statistical methods for testing effects on "maximum lifespan". Mech Ageing Dev. 2004;125:629-632. doi: 10.1016/j.mad.2004.07.003
30. Houde VP, Brule S, Festuccia WT, et al. Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. Diabetes. 2010;59:1338-1348. doi: 10.2337/db09-1324
31. Cunningham JT, Rodgers JT, Arlow DH, Vazquez F, Mootha VK, Puigserver P. mTOR controls mitochondrial oxidative function through a YY1-PGC-1alpha transcriptional complex. Nature. 2007;450:736-740. doi: 10.1038/nature06322
32. Fang Y, Bartke A. Prolonged rapamycin treatment led to beneficial metabolic switch. Aging. 2013;5:328-329.
33. Fang Y, Westbrook R, Hill C, et al. Duration of rapamycin treatment has differential effects on metabolism in mice. Cell Metab. 2013;17:456-462. doi: 10.1016/j.cmet.2013.02.008
34. Leontieva OV, Paszkiewicz GM, Blagosklonny MV. Weekly administration of rapamycin improves survival and biomarkers in obese male mice on high-fat diet. Aging Cell. 2014;13:616-622. doi: 10.1111/acel.12211
35. Makki K, Taront S, Molendi-Coste O, et al. Beneficial metabolic effects of rapamycin are associated with enhanced regulatory cells in dietinduced obese mice. PLoS One. 2014;9:e92684. doi: 10.1371/journal.pone.0092684
36. Blagosklonny MV. Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to. Aging. 2012;4:350-358.
37. Longo VD, Fontana L. Intermittent supplementation with rapamycin as a dietary restriction mimetic. Aging. 2011;3:1039-1040.
38. Mannick JB, Del Giudice G, Lattanzi M, et al. mTOR inhibition improves immune function in the elderly. Sci Transl Med. 2014;6:268ra179. doi: 10.1126/scitranslmed.3009892
39. Fok WC, Chen Y, Bokov A, et al. Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome. PLoS One. 2014;9:e83988. doi: 10.1371/journal.pone.0083988
40. Kleinert M, Sylow L, Fazakerley DJ, et al. Acute mTOR inhibition induces insulin resistance and alters substrate utilization in vivo. Mol Metabol. 2014;3:630-641. doi: 10.1016/j.molmet.2014.06.004
41. Deblon N, Bourgoin L, Veyrat-Durebex C, et al. Chronic mTOR inhibition by rapamycin induces muscle insulin resistance despite weight loss in rats. Br J Pharmacol. 2012;165:2325-2340. doi: 10.1111/j.1476- 5381.2011.01716.x
42. Neff F, Flores-Dominguez D, Ryan DP, et al. Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest. 2013;123:3272-3291. doi: 10.1172/JCI67674
43. Tran CM, Mukherjee S, Ye L, et al. Rapamycin blocks induction of the thermogenic program in white adipose tissue. Diabetes. 2016. doi: 10.2337/db15-0502
44. Hurez V, Dao V, Liu A, et al. Chronic mTOR inhibition in mice with rapamycin alters T, B, myeloid, and innate lymphoid cells and gut flora and prolongs life of immune-deficient mice. Aging Cell. 2015;14:945-956. doi: 10.1111/acel.12380