MTOR's Role in Ageing: Protein Synthesis or Autophagy?

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2010 Feb 17

PMID 20157541

Citations 89

Authors

Sarah L Hands

Christopher G Proud

Andreas Wyttenbach

Affiliations

Soon will be listed here.

Abstract

The molecular and cellular mechanisms that regulate ageing are currently under scrutiny because ageing is linked to many human diseases. The nutrient sensing TOR pathway is emerging as a key regulator of ageing. TOR signaling is complex affecting several crucial cellular functions and two such functions, which show clear effects on ageing, are protein synthesis and autophagy. In this article we discuss the relative importance of both these processes in ageing, identify how TOR regulates translation and autophagy and speculate on links between the TOR signaling network and ageing pathways.

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References

Blagosklonny M, Hall M . Growth and aging: a common molecular mechanism. Aging (Albany NY). 2010; 1(4):357-62. PMC: 2806018. DOI: 10.18632/aging.100040. View

Jung C, Jun C, Ro S, Kim Y, Otto N, Cao J . ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell. 2009; 20(7):1992-2003. PMC: 2663920. DOI: 10.1091/mbc.e08-12-1249. View

Rohde J, Heitman J, Cardenas M . The TOR kinases link nutrient sensing to cell growth. J Biol Chem. 2001; 276(13):9583-6. DOI: 10.1074/jbc.R000034200. View

Blagosklonny M . Aging: ROS or TOR. Cell Cycle. 2008; 7(21):3344-54. DOI: 10.4161/cc.7.21.6965. View

Sarkar S, Rubinsztein D . Inositol and IP3 levels regulate autophagy: biology and therapeutic speculations. Autophagy. 2006; 2(2):132-4. DOI: 10.4161/auto.2387. View

Donati A, Cavallini G, Paradiso C, Vittorini S, Pollera M, Gori Z . Age-related changes in the regulation of autophagic proteolysis in rat isolated hepatocytes. J Gerontol A Biol Sci Med Sci. 2001; 56(7):B288-93. DOI: 10.1093/gerona/56.7.b288. View

Bauer J, Chang C, Morris S, Hozier S, Andersen S, Waitzman J . Expression of dominant-negative Dmp53 in the adult fly brain inhibits insulin signaling. Proc Natl Acad Sci U S A. 2007; 104(33):13355-60. PMC: 1948898. DOI: 10.1073/pnas.0706121104. View

Kaeberlein M, Powers 3rd R, Steffen K, Westman E, Hu D, Dang N . Regulation of yeast replicative life span by TOR and Sch9 in response to nutrients. Science. 2005; 310(5751):1193-6. DOI: 10.1126/science.1115535. View

Kapahi P, Zid B, Harper T, Koslover D, Sapin V, Benzer S . Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol. 2004; 14(10):885-90. PMC: 2754830. DOI: 10.1016/j.cub.2004.03.059. View

10.

Melendez A, Talloczy Z, Seaman M, Eskelinen E, Hall D, Levine B . Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science. 2003; 301(5638):1387-91. DOI: 10.1126/science.1087782. View

11.

King M, Hands S, Hafiz F, Mizushima N, Tolkovsky A, Wyttenbach A . Rapamycin inhibits polyglutamine aggregation independently of autophagy by reducing protein synthesis. Mol Pharmacol. 2008; 73(4):1052-63. DOI: 10.1124/mol.107.043398. View

12.

Buttgereit F, Brand M . A hierarchy of ATP-consuming processes in mammalian cells. Biochem J. 1995; 312 ( Pt 1):163-7. PMC: 1136240. DOI: 10.1042/bj3120163. View

13.

Wang X, Proud C . The mTOR pathway in the control of protein synthesis. Physiology (Bethesda). 2006; 21:362-9. DOI: 10.1152/physiol.00024.2006. View

14.

Juhasz G, Puskas L, Komonyi O, Erdi B, Maroy P, Neufeld T . Gene expression profiling identifies FKBP39 as an inhibitor of autophagy in larval Drosophila fat body. Cell Death Differ. 2007; 14(6):1181-90. PMC: 2084463. DOI: 10.1038/sj.cdd.4402123. View

15.

Schieke S, Phillips D, McCoy Jr J, Aponte A, Shen R, Balaban R . The mammalian target of rapamycin (mTOR) pathway regulates mitochondrial oxygen consumption and oxidative capacity. J Biol Chem. 2006; 281(37):27643-52. DOI: 10.1074/jbc.M603536200. View

16.

Kamada Y, Funakoshi T, Shintani T, Nagano K, Ohsumi M, Ohsumi Y . Tor-mediated induction of autophagy via an Apg1 protein kinase complex. J Cell Biol. 2000; 150(6):1507-13. PMC: 2150712. DOI: 10.1083/jcb.150.6.1507. View

17.

Finkel T, Serrano M, Blasco M . The common biology of cancer and ageing. Nature. 2007; 448(7155):767-74. DOI: 10.1038/nature05985. View

18.

Zhang Y, Nomura M, Zhong S, Chen N, Bode A, Dong Z . Signal transduction pathways involved in phosphorylation and activation of p70S6K following exposure to UVA irradiation. J Biol Chem. 2001; 276(24):20913-23. DOI: 10.1074/jbc.M009047200. View

19.

Majeski A, Dice J . Mechanisms of chaperone-mediated autophagy. Int J Biochem Cell Biol. 2004; 36(12):2435-44. DOI: 10.1016/j.biocel.2004.02.013. View

20.

Ganley I, Lam D, Wang J, Ding X, Chen S, Jiang X . ULK1.ATG13.FIP200 complex mediates mTOR signaling and is essential for autophagy. J Biol Chem. 2009; 284(18):12297-305. PMC: 2673298. DOI: 10.1074/jbc.M900573200. View