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Senescence Regulation by mTOR

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Cell Senescence

Part of the book series: Methods in Molecular Biology ((MIMB,volume 965))

Abstract

The senescence program is activated in response to diverse stress stimuli potentially compromising genetic stability and leads to an irreversible cell cycle arrest. The mTOR pathway plays a crucial role in the regulation of cell metabolism and cellular growth. The goal of this chapter is to present evidence linking these two processes, which have one common regulator—the tumor suppressor p53. While the role of mTOR in senescence is still controversial, recent papers have shed new light onto this issue. This review, far from being exhaustive given the complexity of the field, will hopefully stimulate further research in this domain, whose relevance for ageing is becoming increasingly documented.

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Abbreviations

ARF:

Alternative reading frame

ATM:

Ataxia telangiectasia mutated

ATR:

ATM and Rad3-related kinase

Bmi1:

B lymphoma Mo-MLV insertion region 1

Cdc25:

Cell division cycle 25 (CDK-activating phosphatase)

CDK:

Cyclin-dependent kinase

Chk1/2:

Checkpoint kinase 1/2

CKI:

CDK inhibitor

ERK1/2:

Extracellular regulated kinase (also called MAPK)

FOXO:

Forkhead box protein O

FKBP12:

Peptidyl-prolyl cis/trans isomerase that forms a complex with rapamycin

HES1:

Hairy enhancer of Split1

IGF:

Insulin-like growth factors

IRS:

Insulin receptor substrate

INK4A:

Inhibitor of Cdk4 A

MAPK:

Mitogen-activated protein kinase

mTOR:

Mechanistic (mammalian) target of rapamycin

TORC1/2:

TOR complex 1 and 2

PcG:

Polycomb group

PDK1:

3-Phosphoinositide-dependent kinase 1

PI3K:

Phosphoinositide 3-kinase

PIKK:

Phosphoinositide 3-kinase (PI3K)-related protein serine/threonine kinase family

PML:

Promyelocytic leukemia protein

PTEN:

Phosphatase and tensin homologue

pRb:

Retinoblastoma protein

RHEB:

Ras homologue enriched in brain

SAHF:

Senescence-associated heterochromatin foci

SASP:

Senescence-associated secretory phenotype

SGK:

Serum- and glucocorticoid-regulated kinase

TSC1/2:

Tuberous sclerosis 1,2 GTPase

TGFβ:

Transforming growth factor β

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Acknowledgments

I am grateful to Drs Anne Brunet (Stanford University, Palo Alto, USA) and Jacques Piette (CRBM, Montpellier, France) for their insightful comments.

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Authors and Affiliations

  1. Institut de Génétique Moléculaire, Montpellier, France

    Vjekoslav Dulic

  2. CNRS, UMR5535, Montpellier, France

    Vjekoslav Dulic

  3. Université Montpellier 1, Montpellier, France

    Vjekoslav Dulic

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  1. Vjekoslav Dulic
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Correspondence to Vjekoslav Dulic .

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Editors and Affiliations

  1. Institut Gustave Roussy, Pavillon de Recherche 1, INSERM U848, rue C. Desmoulins 39, Villejuif, 94085, France

    Lorenzo Galluzzi

  2. Institut Gustave Roussy, Pavillon de Recherche 1, INSERM U848, rue C. Desmoulins 39, Villejuif CEDEX, 94085, France

    Ilio Vitale

  3. Institut Gustave Roussy, Pavillon de Recherche 1, INSERM U848, rue C. Desmoulins 39, Villejuif CEDEX, 94085, France

    Oliver Kepp

  4. Institut Gustave Roussy (IGR), Pavillon de Recherche 1, INSERM, U848, rue Camille-Desmoulins 39, Villejuif, 94805, France

    Guido Kroemer

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Dulic, V. (2013). Senescence Regulation by mTOR. In: Galluzzi, L., Vitale, I., Kepp, O., Kroemer, G. (eds) Cell Senescence. Methods in Molecular Biology, vol 965. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-239-1_2

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  • DOI: https://doi.org/10.1007/978-1-62703-239-1_2

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-238-4

  • Online ISBN: 978-1-62703-239-1

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