Fasting levels of hepatic p-S6 are increased in old mice

References

• Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P, Hall MN. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 2002; 10:457-68; PMID:12408816
   PubMed Web of Science ®Google Scholar
• Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18:1926-45; PMID:15314020
   PubMed Web of Science ®Google Scholar
• Loewith R, Hall MN. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 2011; 189:1177-1201; PMID:22174183; http://dx.doi.org/10.1534/genetics.111.133363
   PubMed Web of Science ®Google Scholar
• Sengupta S, Peterson TR, Sabatini DM. Regulation of the mTOR complex 1 pathway by nutrients, growth factors, and stress. Mol Cell 2010;40:310-322; PMID:20965424; http://dx.doi.org/10.1016/j.molcel.2010.09.026
   PubMed Web of Science ®Google Scholar
• Blagosklonny MV. Aging-suppressants: cellular senescence (hyperactivation) and its pharmacologic deceleration. Cell Cycle 2009;8:1883-1887; PMID:19448395
   PubMed Web of Science ®Google Scholar
• Blagosklonny MV, Hall MN. Growth and aging: a common molecular mechanism. Aging 2009; 1:357-362; PMID:20157523
   PubMedGoogle Scholar
• Dazert E, Hall MN. mTOR signaling in disease. Curr Opin Cell Biol 2011; 23(6):744-55; PMID:21963299; http://dx.doi.org/10.1016/j.ceb.2011.09.003
   PubMed Web of Science ®Google Scholar
• Blagosklonny MV. Prospective treatment of age-related diseases by slowing down aging. Am J Pathol 2012;181: 1142-1146; PMID:22841821; http://dx.doi.org/10.1016/j.ajpath.2012.06.024
   PubMed Web of Science ®Google Scholar
• Kaeberlein M. Longevity and aging. F1000Prime Rep. 2013; 5:5; PMID:23513177; http://dx.doi.org/10.12703/P5-5
   PubMedGoogle Scholar
• Johnson SC, Rabinovitch PS, Kaeberlein M. mTOR is a key modulator of ageing and age-related disease. Nature 2013;493:338-345; PMID:23325216; http://dx.doi.org/10.1038/nature11861
   PubMed Web of Science ®Google Scholar
• 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 heterogenous mice. Nature 2009;460:392-396; PMID:19587680; http://dx.doi.org/10.1038/nature08221
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• 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;10:4230-4236; PMID:22107964; http://dx.doi.org/10.4161/cc.10.24.18486
   PubMed Web of Science ®Google Scholar
• 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 AC-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
   PubMed Web of Science ®Google Scholar
• Fok WC, Chen Y, Bokov A, Zhang Y, Salmon AB, Diaz V, Javors M, Wood WH III, Zhang Y, Becker KG, et al. Mice fed rapamycin have an increase in lifespan associated with major changes in the liver transcriptome. PLoS One 2013;9:e83988; PMID:24409289; http://dx.doi.org/10.1371/journal.pone.0083988
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Spong A, Bartke A. Rapamycin slows aging in mice. Cell Cycle 2012;11. 845; PMID:22356747; http://dx.doi.org/10.4161/cc.11.5.19607
   PubMed Web of Science ®Google Scholar
• 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 appears metabolically distinct from dietary restriction. Aging Cell 2013; 13(3):468-77; PMID:24341993; http://dx.doi.org/10.1111/acel.12194
   PubMed Web of Science ®Google Scholar
• Selman C, Partridge L. A double whammy for aging? Rapamycin extends lifespan and inhibits cancer in inbred female mice. Cell Cycle 2012;11:17-18; PMID:22186783; http://dx.doi.org/10.4161/cc.11.1.18736
   PubMed Web of Science ®Google Scholar
• 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 C57BL6 mice. J Gerontol A Biol Sci Med Sci 2014;69:119-130; PMID:23682161; http://dx.doi.org/10.1093/gerona/glt056
   PubMed Web of Science ®Google Scholar
• Popovich IG, Anisimov VN, Zabezhinski MA, Semenchenko AV, Tyndyk ML, Yurova MN, Blagosklonny MV. Lifespan extension and cancer prevention in HER-2neu transgenic mice treated with low intermittent doses of rapamycin. Cancer Biol Ther 2014;15:586-592; PMID:24556924; http://dx.doi.org/10.4161/cbt.28164
   PubMed Web of Science ®Google Scholar
• Blagosklonny MV. mTOR-driven aging: speeding car without brakes. Cell Cycle 2009;8:4055-4059; PMID:19923900
   PubMed Web of Science ®Google Scholar
• Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C. Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 2007;6:95-110; PMID:17266679
   PubMed Web of Science ®Google Scholar
• Pan KZ, Palter JE, Rogers AN, Olsen A, Chen D, Lithgow GJ, Kapahi P. Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 2007;6:111-119; PMID:17266680
   PubMed Web of Science ®Google Scholar
• Kaeberlein M, Kennedy BK. Hot topics in aging research: protein translation and TOR signaling, 2010. Aging Cell 2011;10:185-90; PMID:21176090; http://dx.doi.org/10.1111/j.1474-9726.2010.00665.x
   PubMed Web of Science ®Google Scholar
• Mehta R, Chandler-Brown D, Ramos FJ, Shamieh LS, Kaeberlein M. Regulation of mRNA translation as a conserved mechanism of longevity control. Adv Exp Med Biol 2011;694:14-29; PMID:20886753
   PubMed Web of Science ®Google Scholar
• Pospelova TV, Demidenko ZN, Bukreeva EI, Pospelov VA, Gudkov AV, Blagosklonny MV. Pseudo-DNA damage response in senescent cells. Cell Cycle 2009;8:4112-8; PMID:19946210
   PubMed Web of Science ®Google Scholar
• Leontieva OV, Demidenko ZN, Blagosklonny MV. MEK drives cyclin D1 hyperelevation during geroconversion. Cell Death Diff. 2013;20:1241-9; PMID:23852369; http://dx.doi.org/10.1038/cdd.2013.86
   PubMed Web of Science ®Google Scholar
• Leontieva OV, Blagosklonny MV. CDK46-inhibiting drug substitutes for p21 and p16 in senescence: duration of cell cycle arrest and MTOR activity determine geroconversion. Cell Cycle 2013;12:3063-9; PMID:23974099; http://dx.doi.org/10.4161/cc.26130
   PubMed Web of Science ®Google Scholar
• Leontieva OV, Blagosklonny MV. M(o)TOR of pseudo-hypoxic state in aging: rapamycin to the rescue. Cell Cycle 2014;13:(4):509-15; PMID:24496328; http://dx.doi.org/10.4161/cc.27973
   PubMed Web of Science ®Google Scholar
• Blagosklonny MV. Cell cycle arrest is not yet senescence, which is not just cell cycle arrest: terminology for TOR-driven aging. Aging (Albany NY) 2012;4:159-65; PMID:22394614
   PubMedGoogle Scholar
• Cho S, Hwang ES. Status of mTOR activity may phenotypically differentiate senescence and quiescence. Mol Cells 2012;33:597-604; PMID:22570149; http://dx.doi.org/10.1007/s10059-012-0042-1
   PubMed Web of Science ®Google Scholar
• Demidenko ZN, Korotchkina LG, Gudkov AV, Blagosklonny MV. Paradoxical suppression of cellular senescence by p53. Proc Natl Acad Sci U S A 2010;107:9660-4; PMID:20457898; http://dx.doi.org/10.1073/pnas.1002298107
   PubMed Web of Science ®Google Scholar
• Leontieva OV, Natarajan V, Demidenko ZN, Burdelya LG, Gudkov AV, Blagosklonny MV. Hypoxia suppresses conversion from proliferative arrest to cellular senescence. Proc Natl Acad Sci U S A 2012;109:13314-8; PMID:22847439; http://dx.doi.org/10.1073/pnas.1205690109
   PubMed Web of Science ®Google Scholar
• Kolesnichenko M, Hong L, Liao R, Vogt PK, Sun P. Attenuation of TORC1 signaling delays replicative and oncogenic RAS-induced senescence. Cell Cycle 2012;11:2391-401; PMID:22627671; http://dx.doi.org/10.4161/cc.20683
   PubMed Web of Science ®Google Scholar
• Serrano M. Dissecting the role of mTOR complexes in cellular senescence. Cell Cycle 2012;11:2231-2; PMID:22714590; http://dx.doi.org/10.4161/cc.21065
   PubMed Web of Science ®Google Scholar
• 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
   PubMed Web of Science ®Google Scholar
• Dulic V. Senescence regulation by mTOR. Methods Mol Biol 2013;965:15-35; PMID:23296649; http://dx.doi.org/10.1007/978-1-62703-239-1_2
   PubMedGoogle Scholar
• Leontieva OV, Demidenko ZN, Blagosklonny MV. Contact inhibition and high cell density deactivate the mammalian target of rapamycin pathway, thus suppressing the senescence program. Proc Natl Acad Sci U S A 2014; 111:8832-7; PMID:24889617; http://dx.doi.org/10.1073/pnas.1405723111
   PubMed Web of Science ®Google Scholar
• Hinojosa CA, Mgbemena V, Van Roekel S, Austad SN, Miller RA, Bose S, Orihuela CJ. Enteric-delivered rapamycin enhances resistance of aged mice to pneumococcal pneumonia through reduced cellular senescence. Exp Gerontol 2012;47:958-65; PMID:22981852; http://dx.doi.org/10.1016/j.exger.2012.08.013
   PubMed Web of Science ®Google Scholar
• Leontieva OV, Demidenko ZN, Blagosklonny MV. Rapamycin reverses insulin resistance (IR) in high-glucose medium without causing IR in normoglycemic medium. Cell Death Dis 2014;5:e1214; PMID:24810050; http://dx.doi.org/10.1038/cddis.2014.178
   PubMed Web of Science ®Google Scholar
• Sengupta S, Peterson TR, Laplante M, Oh S, Sabatini DM. mTORC1 controls fasting-induced ketogenesis and its modulation by ageing. Nature 2010;468:1100-4; PMID:21179166; http://dx.doi.org/10.1038/nature09584
   PubMed Web of Science ®Google Scholar
• Speakman JR, Hambly C. Starving for life: what animal studies can and cannot tell us about the use of caloric restriction to prolong human lifespan. J Nutr 2007;137:1078-86; PMID:17374682
   PubMed Web of Science ®Google Scholar
• Stanfel MN, Shamieh LS, Kaeberlein M, Kennedy BK. The TOR pathway comes of age. Biochim Biophys Acta 2009;1790:1067-1074; PMID:19539012; http://dx.doi.org/10.1016/j.bbagen.2009.06.007
   PubMed Web of Science ®Google Scholar
• Blagosklonny MV. Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans). Cell Cycle 2010;9:683-8; PMID:20139716
   PubMed Web of Science ®Google Scholar
• Mercken EM, Carboneau BA, Krzysik-Walker SM, de Cabo R. Of mice and men: the benefits of caloric restriction, exercise, and mimetics. Ageing Res Rev 2012;11:390-8; PMID:22210414; http://dx.doi.org/10.1016/j.arr.2011.11.005
   PubMed Web of Science ®Google Scholar
• Kaeberlein M, Kennedy BK. Ageing: a midlife longevity drug? Nature. 2009;460:331-2; PMID:19606132; http://dx.doi.org/10.1038/460331a
   PubMed Web of Science ®Google Scholar
• Cava E, Fontana L. Will calorie restriction work in humans? Aging (Albany NY) 2013; 5:507-14; PMID:23924667
   PubMedGoogle Scholar
• Emran S, Yang M, He X, Zandveld J, Piper MD. Target of rapamycin signaling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration. Aging (Albany NY) 2014; 6:390-8; PMID:24861087
   PubMedGoogle Scholar
• Weindruch R, Walford RL. Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science 1982;215:1415-8; PMID:7063854
   PubMed Web of Science ®Google Scholar
• Levine ME, Suarez JA, Brandhorst S, Balasubramanian P, Cheng CW, Madia F, Fontana L, Mirisola MG, Guevara-Aguirre J, Wan J, et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab 2014;19:407-17; PMID:24606898; http://dx.doi.org/10.1016/j.cmet.2014.02.006
   PubMed Web of Science ®Google Scholar
• Chen C, 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
   PubMed Web of Science ®Google Scholar
• Fry CS, Drummond MJ, Glynn EL, Dickinson JM, Gundermann DM, Timmerman KL, Walker DK, Dhanani S, Volpi E, Rasmussen BB. Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Skelet Muscle 2011;1:11; PMID:21798089; http://dx.doi.org/10.1186/2044-5040-1-11
   PubMed Web of Science ®Google Scholar
• D’Antona G, Nisoli E. mTOR signaling as a target of amino acid treatment of the age-related sarcopenia. Interdiscip Top Gerontol 2010;37:115-41; PMID:20703059; http://dx.doi.org/10.1159/000319998
   PubMedGoogle Scholar
• Sandri M, Barberi L, Bijlsma AY, Blaauw B, Dyar KA, Milan G, Mammucari C, Meskers CG, Pallafacchina G, Paoli A, et al. Signalling pathways regulating muscle mass in ageing skeletal muscle: the role of the IGF1-Akt-mTOR-FoxO pathway. Biogerontology 2014;14:303-23; PMID:23686362; http://dx.doi.org/10.1007/s10522-013-9432-9
   PubMed Web of Science ®Google Scholar
• 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
   PubMedGoogle Scholar
• 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 Mar 22; 13(4):616-22; PMID:24655348; http://dx.doi.org/10.1111/acel.12211.
   PubMed Web of Science ®Google Scholar