Transient rapamycin treatment can increase lifespan and healthspan in middle-aged mice

eLife

Volumn 5, Issue AUGUST, 2016, Pages

  Bitto, Alessandro ^a   Ito, Takashi K ^a   Pineda, Victor V ^a   Letexier, Nicolas J ^a   Huang, Heather Z ^a   Sutlief, Elissa ^a   Tung, Herman ^a   Vizzini, Nicholas ^a   Chen, Belle ^a   Smith, Kaleb ^a   Meza, Daniel ^a   Yajima, Masanao ^b   Beyer, Richard P ^a   Kerr, Kathleen F ^a   Davis, Daniel J ^c   Gillespie, Catherine H ^c   Snyder, Jessica M ^a   Treuting, Piper M ^a   Kaeberlein, Matt ^a  

^a UNIVERSITY OF WASHINGTON   (United States)

^b USA   (United States)

^c UNIVERSITY OF MISSOURI   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

RAPAMYCIN; ANTIINFECTIVE AGENT; ANTINEOPLASTIC ANTIBIOTIC;

ADULT; ANGIOSARCOMA; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BODY WEIGHT; CONTROLLED STUDY; FEMALE; FOOD INTAKE; FORELIMB; GRIP STRENGTH TEST; HEMATOPOIETIC SYSTEM TUMOR; HISTIOCYTIC SARCOMA; HISTOPATHOLOGY; LIFE EXPECTANCY; LIFESPAN; LIVER CELL CARCINOMA; LUNG ADENOMA; LYMPHOMA; MALE; MICROBIOME; MIDDLE AGED; MOUSE; NONHUMAN; REAL TIME POLYMERASE CHAIN REACTION; ROTAROD TEST; SURVIVAL; THYROID ADENOMA; ANIMAL; DRUG EFFECTS; INTESTINE FLORA; LONGEVITY; NEOPLASMS;

ANIMALS; ANTI-BACTERIAL AGENTS; ANTIBIOTICS, ANTINEOPLASTIC; GASTROINTESTINAL MICROBIOME; LONGEVITY; MICE; NEOPLASMS; SIROLIMUS;

EID: 84983670652     PISSN: None     EISSN: 2050084X     Source Type: Journal    
DOI: 10.7554/eLife.16351     Document Type: Article

References (34)

1. Anderson MJ. 2001. A new method for non-parametric multivariate analysis of variance. Austral Ecology 26:32–46. doi: 10.1111/j.1442-9993.2001.01070.pp.x
2. Anisimov VN, Zabezhinski MA, Popovich IG, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Rosenfeld SV, Blagosklonny MV. 2011. Rapamycin increases lifespan and inhibits spontaneous tumorigenesis in inbred female mice. Cell Cycle 10:4230–4236. doi: 10.4161/cc.10.24.18486
3. Atarashi K, Tanoue T, Ando M, Kamada N, Nagano Y, Narushima S, Suda W, Imaoka A, Setoyama H, Nagamori T, Ishikawa E, Shima T, Hara T, Kado S, Jinnohara T, Ohno H, Kondo T, Toyooka K, Watanabe E, Yokoyama S, et al. 2015. Th17 Cell Induction by Adhesion of Microbes to Intestinal Epithelial Cells. Cell 163:367–380. doi: 10.1016/j.cell.2015.08.058
4. Augustine JJ, Bodziak KA, Hricik DE. 2007. Use of sirolimus in solid organ transplantation. Drugs 67:369–391. doi: 10.2165/00003495-200767030-00004
5. Bates D, Mächler M, Bolker B, Walker S. 2014. Fitting linear mixed-effects models using lme4. arXiv:1406.5823 https://arxiv.org/abs/1406.5823.
6. Blackwell BN, Bucci TJ, Hart RW, Turturro A. 1995. Longevity, body weight, and neoplasia in ad libitum-fed and diet-restricted C57BL6 mice fed NIH-31 open formula diet. Toxicologic Pathology 23:570–582. doi: 10.1177/019262339502300503
7. Chen C, Liu Y, Liu Y, Zheng P. 2009. mTOR regulation and therapeutic rejuvenation of aging hematopoietic stem cells. Science Signaling 2:ra75. doi: 10.1126/scisignal.2000559
8. Dai DF, Karunadharma PP, Chiao YA, Basisty N, Crispin D, Hsieh EJ, Chen T, Gu H, Djukovic D, Raftery D, Beyer RP, MacCoss MJ, Rabinovitch PS. 2014. Altered proteome turnover and remodeling by short-term caloric restriction or rapamycin rejuvenate the aging heart. Aging Cell 13:529–539. doi: 10.1111/acel.12203
9. de Oliveira MA, Martins E Martins F, Wang Q, Sonis S, Demetri G, George S, Butrynski J, Treister NS. 2011. Clinical presentation and management of mTOR inhibitor-associated stomatitis. Oral Oncology 47:998–1003. doi: 10.1016/j.oraloncology.2011.08.009
10. Ericsson AC, Davis DJ, Franklin CL, Hagan CE. 2015. Exoelectrogenic capacity of host microbiota predicts lymphocyte recruitment to the gut. Physiological Genomics 47:243–252. doi: 10.1152/physiolgenomics.00010.2015
11. Ericsson AC, Hagan CE, Davis DJ, Franklin CL. 2014. Segmented filamentous bacteria: commensal microbes with potential effects on research. Comparative Medicine 64:90–98.
12. Flynn JM, O’Leary MN, Zambataro CA, Academia EC, Presley MP, Garrett BJ, Zykovich A, Mooney SD, Strong R, Rosen CJ, Kapahi P, Nelson MD, Kennedy BK, Melov S. 2013. Late-life rapamycin treatment reverses age-related heart dysfunction. Aging Cell 12:851–862. doi: 10.1111/acel.12109
13. Goldman DP, Cutler D, Rowe JW, Michaud P-C, Sullivan J, Peneva D, Olshansky SJ. 2013. Substantial health and economic returns from delayed aging may warrant a new focus for medical research. Health Affairs 32:1698–1705. doi: 10.1377/hlthaff.2013.0052
14. Halloran J, Hussong SA, Burbank R, Podlutskaya N, Fischer KE, Sloane LB, Austad SN, Strong R, Richardson A, Hart MJ, Galvan V. 2012. Chronic inhibition of mammalian target of rapamycin by rapamycin modulates cognitive and non-cognitive components of behavior throughout lifespan in mice. Neuroscience 223:102–113. doi: 10.1016/j.neuroscience.2012.06.054
15. Hard GC, Snowden RT. 1991. Hyaline droplet accumulation in rodent kidney proximal tubules: an association with histiocytic sarcoma. Toxicologic Pathology 19:88–97. doi: 10.1177/019262339101900202
16. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA. 2009. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392–395. doi: 10.1038/nature08221
17. Hothorn T, Bretz F, Westfall P. 2008. Simultaneous inference in general parametric models. Biometrical Journal 50:346–363. doi: 10.1002/bimj.200810425
18. Johnson SC, Rabinovitch PS, Kaeberlein M. 2013. mTOR is a key modulator of ageing and age-related disease. Nature 493:338–345. doi: 10.1038/nature11861
19. Johnson SC, Yanos ME, Bitto A, Castanza A, Gagnidze A, Gonzalez B, Gupta K, Hui J, Jarvie C, Johnson BM, Letexier N, McCanta L, Sangesland M, Tamis O, Uhde L, Van Den Ende A, Rabinovitch PS, Suh Y, Kaeberlein M. 2015. Dose-dependent effects of mTOR inhibition on weight and mitochondrial disease in mice. Frontiers in Genetics 6:247. doi: 10.3389/fgene.2015.00247
20. Johnson SC, Yanos ME, Kayser EB, Quintana A, Sangesland M, Castanza A, Uhde L, Hui J, Wall VZ, Gagnidze A, Oh K, Wasko BM, Ramos FJ, Palmiter RD, Rabinovitch PS, Morgan PG, Sedensky MM, Kaeberlein M. 2013. mTOR inhibition alleviates mitochondrial disease in a mouse model of Leigh syndrome. Science 342:1524–1528. doi: 10.1126/science.1244360
21. Kaeberlein M, Rabinovitch PS, Martin GM. 2015. Healthy aging: The ultimate preventative medicine. Science 350:1191–1193. doi: 10.1126/science.aad3267
22. Lamming DW, Ye L, Katajisto P, Goncalves MD, Saitoh M, Stevens DM, Davis JG, Salmon AB, Richardson A, Ahima RS, Guertin DA, Sabatini DM, Baur JA. 2012. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335:1638–1643. doi: 10.1126/science.1215135
23. Majumder S, Caccamo A, Medina DX, Benavides AD, Javors MA, Kraig E, Strong R, Richardson A, Oddo S. 2012. Lifelong rapamycin administration ameliorates age-dependent cognitive deficits by reducing IL-1b and enhancing NMDA signaling. Aging Cell 11:326–335. doi: 10.1111/j.1474-9726.2011.00791.x
24. Mannick JB, Del Giudice G, Lattanzi M, Valiante NM, Praestgaard J, Huang B, Lonetto MA, Maecker HT, Kovarik J, Carson S, Glass DJ, Klickstein LB. 2014. mTOR inhibition improves immune function in the elderly. Science Translational Medicine 6:268ra179. doi: 10.1126/scitranslmed.3009892
25. Mathew T, Kreis H, Friend P. 2004. Two-year incidence of malignancy in sirolimus-treated renal transplant recipients: results from five multicenter studies. Clinical Transplantation 18:446–449. doi: 10.1111/j.1399-0012.2004.00188.x
26. Miller RA, Harrison DE, Astle CM, Baur JA, Boyd AR, de Cabo R, Fernandez E, Flurkey K, Javors MA, Nelson JF, Orihuela CJ, Pletcher S, Sharp ZD, Sinclair D, Starnes JW, Wilkinson JE, Nadon NL, Strong R. 2011. Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 66A:191–201. doi: 10.1093/gerona/glq178
27. Miller RA, Harrison DE, Astle CM, Fernandez E, Flurkey K, Han M, Javors MA, Li X, Nadon NL, Nelson JF, Pletcher S, Salmon AB, Sharp ZD, Van Roekel S, Winkleman L, Strong R. 2014. Rapamycin-mediated lifespan increase in mice is dose and sex dependent and metabolically distinct from dietary restriction. Aging Cell 13: 468–477. doi: 10.1111/acel.12194
28. Paulson JN, Stine OC, Bravo HC, Pop M. 2013. Differential abundance analysis for microbial marker-gene surveys. Nature Methods 10:1200–1202. doi: 10.1038/nmeth.2658
29. Prakash T, Oshima K, Morita H, Fukuda S, Imaoka A, Kumar N, Sharma VK, Kim SW, Takahashi M, Saitou N, Taylor TD, Ohno H, Umesaki Y, Hattori M. 2011. Complete genome sequences of rat and mouse segmented filamentous bacteria, a potent inducer of th17 differentiation. Cell Host & Microbe 10:273–284. doi: 10.1016/j.chom.2011.08.007
30. Ramos FJ, Chen SC, Garelick MG, Dai DF, Liao CY, Schreiber KH, MacKay VL, An EH, Strong R, Ladiges WC, Rabinovitch PS, Kaeberlein M, Kennedy BK. 2012. Rapamycin reverses elevated mTORC1 signaling in lamin A/C-deficient mice, rescues cardiac and skeletal muscle function, and extends survival. Science Translational Medicine 4:144ra103. doi: 10.1126/scitranslmed.3003802
31. Treuting PM, Linford NJ, Knoblaugh SE, Emond MJ, Morton JF, Martin GM, Rabinovitch PS, Ladiges WC. 2008. Reduction of age-associated pathology in old mice by overexpression of catalase in mitochondria. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 63:813–822. doi: 10.1093/gerona/63.8.813
32. Wilkinson JE, Burmeister L, Brooks SV, Chan CC, Friedline S, Harrison DE, Hejtmancik JF, Nadon N, Strong R, Wood LK, Woodward MA, Miller RA. 2012. Rapamycin slows aging in mice. Aging Cell 11:675–682. doi: 10.1111/j.1474-9726.2012.00832.x
33. Xu M, Tchkonia T, Ding H, Ogrodnik M, Lubbers ER, Pirtskhalava T, White TA, Johnson KO, Stout MB, Mezera V, Giorgadze N, Jensen MD, LeBrasseur NK, Kirkland JL. 2015. JAK inhibition alleviates the cellular senescence-associated secretory phenotype and frailty in old age. PNAS 112:E6301–E6310. doi: 10.1073/pnas.1515386112
34. Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D’Amico D, Ropelle ER, Lutolf MP, Aebersold R, Schoonjans K, Menzies KJ, Auwerx J. 2016. NAD+ repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352:1436–1443. doi: 10.1126/science.aaf2693