title: MicroRegulators come of age in senescence.
abstract: Cellular senescence was first reported five decades ago as a state of long-term growth inhibition in viable, metabolically active cells cultured in vitro. However, evidence that senescence occurs in vivo and underlies pathophysiologic processes has only emerged over the past few years. Coincident with this increased knowledge, understanding of the mechanisms that control senescent-cell gene expression programs has also recently escalated. Such mechanisms include a prominent group of regulatory factors (miRNA), a family of small, noncoding RNAs that interact with select target mRNAs and typically repress their expression. Here, we review recent reports that miRNAs are key modulators of cellular senescence, and we examine their influence upon specific senescence-regulatory proteins. We discuss evidence that dysregulation of miRNA-governed senescence programs underlies age-associated diseases, including cancer.
authors: Laboratory of Molecular Biology and Immunology, NIA-IRP, NIH, 251 Bayview Blvd, Baltimore, MD 21224, USA. myriam-gorospe@nih.gov
authors: Myriam
authors: M
authors: Gorospe
authors: Kotb
authors: K
authors: Abdelmohsen
references: Front Biosci. 2001 Jan 01;6:D26-44
references: 11145924
references: JAMA. 2011 Jan 5;305(1):59-67
references: 21205967
references: Nat Struct Mol Biol. 2006 Dec;13(12):1097-101
references: 17099701
references: Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20297-302
references: 19088191
references: Oncogene. 2008 Oct 9;27(46):5975-87
references: 18711403
references: Proc Natl Acad Sci U S A. 2005 Sep 27;102(39):13944-9
references: 16166262
references: Nat Cell Biol. 2003 Aug;5(8):741-7
references: 12855956
references: Aging (Albany NY). 2010 Jun;2(6):333-43
references: 20606251
references: Mech Ageing Dev. 2009 Nov-Dec;130(11-12):731-41
references: 19782699
references: Cell Death Differ. 2010 Feb;17(2):193-9
references: 19461653
references: Nat Rev Mol Cell Biol. 2009 Feb;10(2):126-39
references: 19165215
references: Curr Opin Immunol. 2009 Aug;21(4):418-24
references: 19570667
references: FEBS Lett. 2008 Apr 30;582(10):1564-8
references: 18406353
references: Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):522-7
references: 21187425
references: Cell. 1997 Mar 7;88(5):593-602
references: 9054499
references: Nature. 2005 Aug 4;436(7051):720-4
references: 16079850
references: Cell Death Differ. 2011 Jun;18(6):974-84
references: 21233845
references: Blood. 2010 Dec 16;116(25):5638-49
references: 20889924
references: Cancer Res. 2007 Sep 15;67(18):8433-8
references: 17823410
references: Biol Chem. 2008 Mar;389(3):243-55
references: 18177264
references: Curr Biol. 1998 Feb 26;8(5):279-82
references: 9501072
references: Sci Signal. 2009 Oct 27;2(94):ra69
references: 19861690
references: Science. 1998 Jan 16;279(5349):349-52
references: 9454332
references: Cell. 2005 Feb 25;120(4):513-22
references: 15734683
references: Aging (Albany NY). 2009 Sep 10;1(9):803-17
references: 20157568
references: Am J Physiol Endocrinol Metab. 2010 Jul;299(1):E110-6
references: 20424141
references: Cancer Lett. 2001 Sep 28;171(1):87-101
references: 11485831
references: Mol Cell. 2009 Sep 11;35(5):610-25
references: 19748357
references: Cell. 2008 Aug 22;134(4):657-67
references: 18724938
references: J Cell Physiol. 2009 Oct;221(1):109-19
references: 19475566
references: PLoS One. 2010 Jun 21;5(6):e10748
references: 20574517
references: Mol Cell. 2007 Jun 8;26(5):745-52
references: 17540599
references: J Biol Chem. 2006 Feb 17;281(7):4339-47
references: 16339764
references: J Cell Biol. 2008 Jun 30;181(7):1055-63
references: 18591425
references: Biochem Biophys Res Commun. 2010 Aug 6;398(4):735-40
references: 20627091
references: Mol Neurodegener. 2010 Mar 24;5:12
references: 20334662
references: PLoS Biol. 2008 Dec 2;6(12):2853-68
references: 19053174
references: Proc Natl Acad Sci U S A. 2008 Sep 9;105(36):13421-6
references: 18755897
references: Nucleic Acids Res. 2007;35(22):7475-84
references: 17942417
references: Cell Cycle. 2007 Jul 1;6(13):1586-93
references: 17554199
references: Exp Cell Res. 1965 Mar;37:614-36
references: 14315085
references: Proc Natl Acad Sci U S A. 2007 Sep 25;104(39):15472-7
references: 17875987
references: Aging (Albany NY). 2009 Apr;1(4):402-11
references: 20148189
references: Nature. 2005 Aug 4;436(7051):725-30
references: 16079851
references: Proc Natl Acad Sci U S A. 2001 Oct 9;98(21):12072-7
references: 11593017
references: J Biol Chem. 2010 Dec 10;285(50):39551-63
references: 20923760
references: Mech Ageing Dev. 2007 Jan;128(1):36-44
references: 17116315
references: Proc Natl Acad Sci U S A. 2005 Aug 2;102(31):10898-903
references: 16040801
references: J Biol Chem. 2003 Apr 4;278(14):11731-4
references: 12551891
references: Int J Biochem Cell Biol. 2005 May;37(5):961-76
references: 15743671
references: Cell. 2008 Jun 13;133(6):1019-31
references: 18555778
references: Mol Cell. 2007 Jun 8;26(5):731-43
references: 17540598
references: Cell. 2008 Jul 25;134(2):215-30
references: 18662538
references: PLoS One. 2008 Mar 26;3(3):e1864
references: 18365017
references: Cancer Res. 1999 Apr 1;59(7):1539-43
references: 10197626
references: Curr Biol. 2007 Aug 7;17(15):1298-307
references: 17656095
references: Cell. 2008 Jun 13;133(6):1006-18
references: 18555777
references: Cell Mol Life Sci. 2011 Jan;68(2):325-36
references: 20652617
references: Annu Rev Biochem. 2010;79:351-79
references: 20533884
references: Cell Death Differ. 2010 Feb;17(2):236-45
references: 19696787
references: Exp Cell Res. 2008 Jun 10;314(9):1918-22
references: 18282568
references: Int J Radiat Oncol Biol Phys. 2011 Nov 1;81(3):839-48
references: 21093163
references: Cell Cycle. 2010 Apr 1;9(7):1354-9
references: 20305372
references: Cell. 2009 Jan 23;136(2):215-33
references: 19167326
references: Nature. 2005 Aug 4;436(7051):660-5
references: 16079837
references: EMBO J. 2004 Oct 13;23(20):4051-60
references: 15372072
references: Am J Respir Cell Mol Biol. 2008 Jul;39(1):7-18
references: 18239191
references: Nature. 2005 Aug 4;436(7051):642
references: 16079833
references: Genes Dev. 2010 Jun 1;24(11):1086-92
references: 20516194
references: Nat Biotechnol. 2002 Jul;20(7):682-8
references: 12089552
references: Proc Natl Acad Sci U S A. 1995 Sep 26;92(20):9363-7
references: 7568133
references: PLoS One. 2010 Sep 01;5(9):
references: 20824140
references: EMBO J. 2003 Aug 15;22(16):4212-22
references: 12912919
references: Mech Ageing Dev. 2004 Oct-Nov;125(10-11):827-48
references: 15541776
references: Science. 2007 Dec 21;318(5858):1931-4
references: 18048652
references: Exp Gerontol. 2003 Nov-Dec;38(11-12):1251-7
references: 14698804
references: J Clin Invest. 2004 Nov;114(9):1299-307
references: 15520862
references: Nat Cell Biol. 2009 Aug;11(8):973-9
references: 19597488
references: Science. 2006 Mar 3;311(5765):1257
references: 16456035
references: Nat Cell Biol. 2008 Mar;10(3):361-9
references: 18297059
references: Cell Cycle. 2011 Mar 1;10(5):751-9
references: 21311220
references: Nat Cell Biol. 2009 Sep;11(9):1135-42
references: 19701195
references: Nature. 2007 Jun 28;447(7148):1130-4
references: 17554337
references: Nat Genet. 2003 Nov;35(3):215-7
references: 14528307
references: Circulation. 2009 Oct 13;120(15):1524-32
references: 19786632
references: Trends Mol Med. 2010 May;16(5):238-46
references: 20444648
references: Cancer Cell. 2006 Dec;10(6):459-72
references: 17157787
references: Urology. 2000 Jul;56(1):160-6
references: 10869659
references: Proc Natl Acad Sci U S A. 2006 Oct 31;103(44):16472-7
references: 17060621
references: Curr Biol. 2006 May 23;16(10):1041-9
references: 16682203
references: Nature. 2007 Feb 8;445(7128):656-60
references: 17251933
references: Genes Dev. 2010 Nov 15;24(22):2463-79
references: 21078816
references: Cell Cycle. 2010 Jul 15;9(14):2726-30
references: 20603603
references: Oncogene. 2010 Apr 15;29(15):2262-71
references: 20101223
references: Wiley Interdiscip Rev RNA. 2010 Sep-Oct;1(2):214-29
references: 21935886
references: Exp Cell Res. 1961 Dec;25:585-621
references: 13905658
references: Nature. 2010 Mar 18;464(7287):374-9
references: 20237562
references: Cell Cycle. 2008 Aug 15;7(16):2591-600
references: 18719384
references: J Biol Chem. 2010 Feb 19;285(8):5461-71
references: 19940135
references: Nat Genet. 2009 May;41(5):544-52
references: 19282848