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Growth or longevity: the TOR’s decision on lifespan regulation

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Abstract

TOR (target of rapamycin) pathway has been well known for its central role in growth control. Interestingly, recent studies also implicate the TOR pathway in lifespan regulation in various organisms ranging from budding yeast to mammals. TOR gains momentum in a study showing that rapamycin administration later in life significantly extends lifespan in mice. How the TOR kinase controls these two seemingly distinct biological processes is an especially intriguing question yet to be answered. Here, we summarize the literatures concerning TOR’s role in growth control, stress response and lifespan regulation, hoping to obtain a better understanding of how cell growth and maintenance are balanced by TOR and how TOR-mediated shift in metabolisms or energy allocations may translate into lifespan extension at the organismal level. We also evaluate the undergoing efforts to target the TOR pathway for health in human, with focus on looking for new drugs that can bypass the unwanted side effects of rapamycin derivatives.

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References

  • Alvers AL, Wood MS, Hu D, Kaywell AC, Dunn WA Jr, Aris JP (2009) Autophagy is required for extension of yeast chronological life span by rapamycin. Autophagy 5(6):847–849

    PubMed  CAS  Google Scholar 

  • Anisimov VN, Berstein LM, Popovich IG, Zabezhinski MA, Egormin PA, Piskunova TS, Semenchenko AV, Tyndyk ML, Yurova MN, Kovalenko IG, Poroshina TE (2011) If started early in life, metformin treatment increases life span and postpones tumors in female SHR mice. Aging (Albany NY) 3(2):148–157

    CAS  Google Scholar 

  • Apfeld J, O’Connor G, McDonagh T, DiStefano PS, Curtis R (2004) The AMP-activated protein kinase AAK-2 links energy levels and insulin-like signals to lifespan in C. elegans. Genes Dev 18(24):3004–3009

    Article  PubMed  CAS  Google Scholar 

  • Ashrafi K, Lin SS, Manchester JK, Gordon JI (2000) Sip2p and its partner snf1p kinase affect aging in S. cerevisiae. Genes Dev 14(15):1872–1885

    PubMed  CAS  Google Scholar 

  • Benjamin D, Colombi M, Moroni C, Hall MN (2011) Rapamycin passes the torch: a new generation of mTOR inhibitors. Nat Rev Drug Discov 10(11):868–880

    Article  PubMed  CAS  Google Scholar 

  • Binda M, Peli-Gulli MP, Bonfils G, Panchaud N, Urban J, Sturgill TW, Loewith R, De Virgilio C (2009) The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell 35(5):563–573

    Article  PubMed  CAS  Google Scholar 

  • Bjedov I, Partridge L (2011) A longer and healthier life with TOR down-regulation: genetics and drugs. Biochem Soc Trans 39(2):460–465

    Article  PubMed  CAS  Google Scholar 

  • Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L (2010) Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab 11(1):35–46

    Article  PubMed  CAS  Google Scholar 

  • Blagosklonny MV (2006) Aging and immortality: quasi-programmed senescence and its pharmacologic inhibition. Cell Cycle 5(18):2087–2102

    Article  PubMed  CAS  Google Scholar 

  • Bonawitz ND, Chatenay-Lapointe M, Pan Y, Shadel GS (2007) Reduced TOR signaling extends chronological life span via increased respiration and upregulation of mitochondrial gene expression. Cell Metab 5(4):265–277

    Article  PubMed  CAS  Google Scholar 

  • Browne GJ, Proud CG (2002) Regulation of peptide-chain elongation in mammalian cells. Eur J Biochem 269(22):5360–5368

    Article  PubMed  CAS  Google Scholar 

  • Brugarolas J, Lei K, Hurley RL, Manning BD, Reiling JH, Hafen E, Witters LA, Ellisen LW, Kaelin WG Jr (2004) Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev 18(23):2893–2904

    Article  PubMed  CAS  Google Scholar 

  • Budanov AV, Karin M (2008) p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 134(3):451–460

    Article  PubMed  CAS  Google Scholar 

  • Chang YY, Neufeld TP (2009) An Atg1/Atg13 complex with multiple roles in TOR-mediated autophagy regulation. Mol Biol Cell 20(7):2004–2014

    Article  PubMed  CAS  Google Scholar 

  • Chen J, Zheng XF, Brown EJ, Schreiber SL (1995) Identification of an 11-kDa FKBP12-rapamycin-binding domain within the 289-kDa FKBP12-rapamycin-associated protein and characterization of a critical serine residue. Proc Natl Acad Sci U S A 92(11):4947–4951

    Article  PubMed  CAS  Google Scholar 

  • Chen D, Thomas EL, Kapahi P (2009) HIF-1 modulates dietary restriction-mediated lifespan extension via IRE-1 in Caenorhabditis elegans. PLoS Genet 5(5):e1000486

    Article  PubMed  Google Scholar 

  • Drenos F, Westendorp RG, Kirkwood TB (2006) Trade-off mediated effects on the genetics of human survival caused by increasingly benign living conditions. Biogerontology 7(4):287–295

    Article  PubMed  Google Scholar 

  • Fabrizio P, Pozza F, Pletcher SD, Gendron CM, Longo VD (2001) Regulation of longevity and stress resistance by Sch9 in yeast. Science 292(5515):288–290

    Article  PubMed  CAS  Google Scholar 

  • Fang Y, Vilella-Bach M, Bachmann R, Flanigan A, Chen J (2001) Phosphatidic acid-mediated mitogenic activation of mTOR signaling. Science 294(5548):1942–1945

    Article  PubMed  CAS  Google Scholar 

  • Fingar DC, Blenis J (2004) Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23(18):3151–3171

    Article  PubMed  CAS  Google Scholar 

  • Ganley IG, du Lam H, Wang J, Ding X, Chen S, Jiang X (2009) ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem 284(18):12297–12305

    Article  PubMed  CAS  Google Scholar 

  • Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30(2):214–226

    Article  PubMed  CAS  Google Scholar 

  • Hansen M, Taubert S, Crawford D, Libina N, Lee SJ, Kenyon C (2007) Lifespan extension by conditions that inhibit translation in Caenorhabditis elegans. Aging Cell 6(1):95–110

    Article  PubMed  CAS  Google Scholar 

  • Hara K, Yonezawa K, Kozlowski MT, Sugimoto T, Andrabi K, Weng QP, Kasuga M, Nishimoto I, Avruch J (1997) Regulation of eIF-4E BP1 phosphorylation by mTOR. J Biol Chem 272(42):26457–26463

    Article  PubMed  CAS  Google Scholar 

  • 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(7253):392–395

    PubMed  CAS  Google Scholar 

  • Hay N, Sonenberg N (2004) Upstream and downstream of mTOR. Genes Dev 18(16):1926–1945

    Article  PubMed  CAS  Google Scholar 

  • Holz MK, Ballif BA, Gygi SP, Blenis J (2005) mTOR and S6K1 mediate assembly of the translation preinitiation complex through dynamic protein interchange and ordered phosphorylation events. Cell 123(4):569–580

    Article  PubMed  CAS  Google Scholar 

  • Honjoh S, Yamamoto T, Uno M, Nishida E (2009) Signalling through RHEB-1 mediates intermittent fasting-induced longevity in C. elegans. Nature 457(7230):726–730

    Article  PubMed  CAS  Google Scholar 

  • Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, Guan JL, Oshiro N, Mizushima N (2009) Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 20(7):1981–1991

    Article  PubMed  CAS  Google Scholar 

  • Houde VP, Brule S, Festuccia WT, Blanchard PG, Bellmann K, Deshaies Y, Marette A (2010) Chronic rapamycin treatment causes glucose intolerance and hyperlipidemia by upregulating hepatic gluconeogenesis and impairing lipid deposition in adipose tissue. Diabetes 59(6):1338–1348

    Article  PubMed  CAS  Google Scholar 

  • Huber A, French SL, Tekotte H, Yerlikaya S, Stahl M, Perepelkina MP, Tyers M, Rougemont J, Beyer AL, Loewith R (2011) Sch9 regulates ribosome biogenesis via Stb3, Dot6 and Tod6 and the histone deacetylase complex RPD3L. EMBO J 30(15):3052–3064

    Article  PubMed  CAS  Google Scholar 

  • Jia K, Chen D, Riddle DL (2004) The TOR pathway interacts with the insulin signaling pathway to regulate C. elegans larval development, metabolism and life span. Development 131(16):3897–3906

    Article  PubMed  CAS  Google Scholar 

  • Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH (2009) ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 20(7):1992–2003

    Article  PubMed  CAS  Google Scholar 

  • Kaeberlein M, Powers RW 3rd, Steffen KK, Westman EA, Hu D, Dang N, Kerr EO, Kirkland KT, Fields S, Kennedy BK (2005) Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science 310(5751):1193–1196

    Article  PubMed  CAS  Google Scholar 

  • Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y (2000) Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol 150(6):1507–1513

    Article  PubMed  CAS  Google Scholar 

  • Kamada Y, Sekito T, Ohsumi Y (2004) Autophagy in yeast: a TOR-mediated response to nutrient starvation. Curr Top Microbiol Immunol 279:73–84

    Article  PubMed  CAS  Google Scholar 

  • Kamada Y, Yoshino K, Kondo C, Kawamata T, Oshiro N, Yonezawa K, Ohsumi Y (2010) Tor directly controls the Atg1 kinase complex to regulate autophagy. Mol Cell Biol 30(4):1049–1058

    Article  PubMed  CAS  Google Scholar 

  • Kantidakis T, Ramsbottom BA, Birch JL, Dowding SN, White RJ (2010) mTOR associates with TFIIIC, is found at tRNA and 5S rRNA genes, and targets their repressor Maf1. Proc Natl Acad Sci U S A 107(26):11823–11828

    Article  PubMed  CAS  Google Scholar 

  • Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14(10):885–890

    Article  PubMed  CAS  Google Scholar 

  • Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang R (1993) A C. elegans mutant that lives twice as long as wild type. Nature 366(6454):461–464

    Article  PubMed  CAS  Google Scholar 

  • Kirkwood TB (1977) Evolution of ageing. Nature 270(5635):301–304

    Article  PubMed  CAS  Google Scholar 

  • Kirkwood TB, Melov S (2011) On the programmed/non-programmed nature of ageing within the life history. Curr Biol 21(18):701–707

    Article  Google Scholar 

  • Kofman AE, McGraw MR, Payne CJ (2012) Rapamycin increases oxidative stress response gene expression in adult stem cells. Aging (Albany NY) 4(4):279–289

    CAS  Google Scholar 

  • Land SC, Tee AR (2007) Hypoxia-inducible factor 1alpha is regulated by the mammalian target of rapamycin (mTOR) via an mTOR signaling motif. J Biol Chem 282(28):20534–20543

    Article  PubMed  CAS  Google Scholar 

  • Lee SJ, Hwang AB, Kenyon C (2010) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20(23):2131–2136

    Article  PubMed  CAS  Google Scholar 

  • Li H, Tsang CK, Watkins M, Bertram PG, Zheng XF (2006) Nutrient regulates Tor1 nuclear localization and association with rDNA promoter. Nature 442(7106):1058–1061

    Article  PubMed  CAS  Google Scholar 

  • Liko D, Conway MK, Grunwald DS, Heideman W (2010) Stb3 plays a role in the glucose-induced transition from quiescence to growth in Saccharomyces cerevisiae. Genetics 185(3):797–810

    Article  PubMed  CAS  Google Scholar 

  • Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo J, Bonenfant D, Oppliger W, Jenoe P, Hall MN (2002) Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10:457–468

    Article  PubMed  CAS  Google Scholar 

  • Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J (2005) Rheb binds and regulates the mTOR kinase. Curr Biol 15(8):702–713

    Article  PubMed  CAS  Google Scholar 

  • Madeo F, Tavernarakis N, Kroemer G (2010) Can autophagy promote longevity? Nat Cell Biol 12(9):842–846

    Article  PubMed  CAS  Google Scholar 

  • Manning BD, Cantley LC (2003) Rheb fills a GAP between TSC and TOR. Trends Biochem Sci 28(11):573–576

    Article  PubMed  CAS  Google Scholar 

  • Mayer C, Grummt I (2006) Ribosome biogenesis and cell growth: mTOR coordinates transcription by all three classes of nuclear RNA polymerases. Oncogene 25(48):6384–6391

    Article  PubMed  CAS  Google Scholar 

  • McMahon LP, Yue W, Santen RJ, Lawrence JC Jr (2005) Farnesylthiosalicylic acid inhibits mammalian target of rapamycin (mTOR) activity both in cells and in vitro by promoting dissociation of the mTOR-raptor complex. Mol Endocrinol 19(1):175–183

    Article  PubMed  CAS  Google Scholar 

  • Michels AA (2011) MAF1: a new target of mTORC1. Biochem Soc Trans 39(2):487–491

    Article  PubMed  CAS  Google Scholar 

  • Michels AA, Robitaille AM, Buczynski-Ruchonnet D, Hodroj W, Reina JH, Hall MN, Hernandez N (2010) mTORC1 directly phosphorylates and regulates human MAF1. Mol Cell Biol 30(15):3749–3757

    Article  PubMed  CAS  Google Scholar 

  • Morrisett JD, Abdel-Fattah G, Hoogeveen R, Mitchell E, Ballantyne CM, Pownall HJ, Opekun AR, Jaffe JS, Oppermann S, Kahan BD (2002) Effects of sirolimus on plasma lipids, lipoprotein levels, and fatty acid metabolism in renal transplant patients. J Lipid Res 43(8):1170–1180

    PubMed  CAS  Google Scholar 

  • Onken B, Driscoll M (2010) Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans healthspan via AMPK, LKB1, and SKN-1. PLoS ONE 5(1):e8758

    Article  PubMed  Google Scholar 

  • Pan Y (2011) Mitochondria, reactive oxygen species, and chronological aging: a message from yeast. Exp Gerontol 46(11):847–852

    Article  PubMed  CAS  Google Scholar 

  • Pan KZ, Palter JE, Rogers AN, Olsen A, Chen D, Lithgow GJ, Kapahi P (2007) Inhibition of mRNA translation extends lifespan in Caenorhabditis elegans. Aging Cell 6(1):111–119

    Article  PubMed  CAS  Google Scholar 

  • Pan Y, Schroeder EA, Ocampo A, Barrientos A, Shadel GS (2011) Regulation of yeast chronological life span by TORC1 via adaptive mitochondrial ROS signaling. Cell Metab 13(6):668–678

    Article  PubMed  CAS  Google Scholar 

  • Pan Y, Nishida Y, Wang M, Verdin E (2012) Metabolic regulation, mitochondria and the life-prolonging effect of rapamycin: a mini-review. Gerontology 58(6):524–530

    Article  PubMed  CAS  Google Scholar 

  • Patel PH, Tamanoi F (2006) Increased Rheb-TOR signaling enhances sensitivity of the whole organism to oxidative stress. J Cell Sci 119(Pt 20):4285–4292

    Article  PubMed  CAS  Google Scholar 

  • Pearce LR, Alton GR, Richter DT, Kath JC, Lingardo L, Chapman J, Hwang C, Alessi DR (2010) Characterization of PF-4708671, a novel and highly specific inhibitor of p70 ribosomal S6 kinase (S6K1). Biochem J 431(2):245–255

    Article  PubMed  CAS  Google Scholar 

  • Powers T (2004) Ribosome biogenesis: giant steps for a giant problem. Cell 119(7):901–902

    PubMed  CAS  Google Scholar 

  • Rajapakse AG, Yepuri G, Carvas JM, Stein S, Matter CM, Scerri I, Ruffieux J, Montani JP, Ming XF, Yang Z (2011) Hyperactive S6K1 mediates oxidative stress and endothelial dysfunction in aging: inhibition by resveratrol. PLoS ONE 6(4):e19237

    Article  PubMed  CAS  Google Scholar 

  • Rattan SI (2008) Increased molecular damage and heterogeneity as the basis of aging. Biol Chem 389(3):267–272

    Article  PubMed  CAS  Google Scholar 

  • Rattan SI (2012) Biogerontology: from here to where? The Lord Cohen Medal lecture-2011. Biogerontology 13(1):83–91

    Article  PubMed  Google Scholar 

  • Reiling JH, Hafen E (2004) The hypoxia-induced paralogs Scylla and Charybdis inhibit growth by down-regulating S6K activity upstream of TSC in Drosophila. Genes Dev 18(23):2879–2892

    Article  PubMed  CAS  Google Scholar 

  • Ristow M, Zarse K (2010) How increased oxidative stress promotes longevity and metabolic health: the concept of mitochondrial hormesis (mitohormesis). Exp Gerontol 45(6):410–418

    Article  PubMed  CAS  Google Scholar 

  • Robida-Stubbs S, Glover-Cutter K, Lamming DW, Mizunuma M, Narasimhan SD, Neumann-Haefelin E, Sabatini DM, Blackwell TK (2012) TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell Metab 15(5):713–724

    Article  PubMed  CAS  Google Scholar 

  • Samaras TT, Elrick H, Storms LH (2003) Birthweight, rapid growth, cancer, and longevity: a review. J Natl Med Assoc 95(12):1170–1183

    PubMed  Google Scholar 

  • Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM (2008) The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320(5882):1496–1501

    Article  PubMed  CAS  Google Scholar 

  • Sarbassov DD, Ali SM, Sabatini DM (2005) Growing roles for the mTOR pathway. Curr Opin Cell Biol 17(6):596–603

    Article  PubMed  CAS  Google Scholar 

  • Schreiber MA, Pierce-Shimomura JT, Chan S, Parry D, McIntire SL (2010) Manipulation of behavioral decline in Caenorhabditis elegans with the Rag GTPase raga-1. PLoS Genet 6(5):e1000972

    Article  PubMed  Google Scholar 

  • Schulz TJ, Zarse K, Voigt A, Urban N, Birringer M, Ristow M (2007) Glucose restriction extends Caenorhabditis elegans life span by inducing mitochondrial respiration and increasing oxidative stress. Cell Metab 6(4):280–293

    Article  PubMed  CAS  Google Scholar 

  • Selman C, Tullet JM, Wieser D, Irvine E, Lingard SJ, Choudhury AI, Claret M, Al-Qassab H, Carmignac D, Ramadani F, Woods A, Robinson IC, Schuster E, Batterham RL, Kozma SC, Thomas G, Carling D, Okkenhaug K, Thornton JM, Partridge L, Gems D, Withers DJ (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326(5949):140–144

    Article  PubMed  CAS  Google Scholar 

  • Steffen KK, MacKay VL, Kerr EO, Tsuchiya M, Hu D, Fox LA, Dang N, Johnston ED, Oakes JA, Tchao BN, Pak DN, Fields S, Kennedy BK, Kaeberlein M (2008) Yeast life span extension by depletion of 60s ribosomal subunits is mediated by Gcn4. Cell 133(2):292–302

    Article  PubMed  CAS  Google Scholar 

  • Strehler BL (1959) Origin and comparison of the effects of time and high-energy radiations on living systems. Q Rev Biol 34(2):117–142

    Article  PubMed  CAS  Google Scholar 

  • Um SH, Frigerio F, Watanabe M, Picard F, Joaquin M, Sticker M, Fumagalli S, Allegrini PR, Kozma SC, Auwerx J, Thomas G (2004) Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431(7005):200–205

    Article  PubMed  CAS  Google Scholar 

  • Urban J, Soulard A, Huber A, Lippman S, Mukhopadhyay D, Deloche O, Wanke V, Anrather D, Ammerer G, Riezman H, Broach JR, De Virgilio C, Hall MN, Loewith R (2007) Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol Cell 26(5):663–674

    Article  PubMed  CAS  Google Scholar 

  • Vellai T, Takacs-Vellai K, Zhang Y, Kovacs AL, Orosz L, Muller F (2003) Genetics: influence of TOR kinase on lifespan in C. elegans. Nature 426(6967):620

    Article  PubMed  CAS  Google Scholar 

  • Veverka V, Crabbe T, Bird I, Lennie G, Muskett FW, Taylor RJ, Carr MD (2008) Structural characterization of the interaction of mTOR with phosphatidic acid and a novel class of inhibitor: compelling evidence for a central role of the FRB domain in small molecule-mediated regulation of mTOR. Oncogene 27(5):585–595

    Article  PubMed  CAS  Google Scholar 

  • Wanke V, Cameroni E, Uotila A, Piccolis M, Urban J, Loewith R, De Virgilio C (2008) Caffeine extends yeast lifespan by targeting TORC1. Mol Microbiol 69(1):277–285

    Article  PubMed  CAS  Google Scholar 

  • Wei Y, Zheng XF (2009) Sch9 partially mediates TORC1 signaling to control ribosomal RNA synthesis. Cell Cycle 8(24):4085–4090

    Article  PubMed  CAS  Google Scholar 

  • Wei Y, Zheng XF (2011) Nutritional control of cell growth via TOR signaling in budding yeast. Methods Mol Biol 759:307–319

    Article  PubMed  CAS  Google Scholar 

  • Wei Y, Tsang CK, Zheng XF (2009) Mechanisms of regulation of RNA polymerase III-dependent transcription by TORC1. EMBO J 28(15):2220–2230

    Article  PubMed  CAS  Google Scholar 

  • Westendorp RG, Kirkwood TB (1998) Human longevity at the cost of reproductive success. Nature 396(6713):743–746

    Article  PubMed  CAS  Google Scholar 

  • Wullschleger S, Loewith R, Hall MN (2006) TOR signaling in growth and metabolism. Cell 124(3):471–484

    Article  PubMed  CAS  Google Scholar 

  • Yang W, Hekimi S (2010) A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol 8(12):e1000556

    Article  PubMed  Google Scholar 

  • Yin D, Chen K (2005) The essential mechanisms of aging: irreparable damage accumulation of biochemical side-reactions. Exp Gerontol 40(6):455–465

    Article  PubMed  CAS  Google Scholar 

  • Yorimitsu T, Klionsky DJ (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ 12(Suppl 2):1542–1552

    Article  PubMed  CAS  Google Scholar 

  • Zarse K, Schmeisser S, Groth M, Priebe S, Beuster G, Kuhlow D, Guthke R, Platzer M, Kahn CR, Ristow M (2012) Impaired insulin/IGF1 signaling extends life span by promoting mitochondrial l-proline catabolism to induce a transient ROS signal. Cell Metab 15(4):451–465

    Article  PubMed  CAS  Google Scholar 

  • Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, Kapahi P (2009) 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139(1):149–160

    Article  PubMed  CAS  Google Scholar 

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Acknowledgments

We apologize for not being able to cite all the relevant publications due to space limit. This work is supported by National Natural Science Foundation of China (NSFC 81200248).

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  1. No.3 People’s Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, 280 Mohe Road, Shanghai, 201900, China

    Yuehua Wei, Yan-Jie Zhang & Ying Cai

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  1. Yuehua Wei
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Correspondence to Yuehua Wei.

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Wei, Y., Zhang, YJ. & Cai, Y. Growth or longevity: the TOR’s decision on lifespan regulation. Biogerontology 14, 353–363 (2013). https://doi.org/10.1007/s10522-013-9435-6

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