title: The aging clock and circadian control of metabolism and genome stability.
abstract: It is widely accepted that aging is characterized by a gradual decline in the efficiency and accuracy of biological processes, leading to deterioration of physiological functions and development of age-associated diseases. Age-dependent accumulation of genomic instability and development of metabolic syndrome are well-recognized components of the aging phenotype, both of which have been extensively studied. Existing findings strongly support the view that the integrity of the cellular genome and metabolic function can be influenced by light at night (LAN) and associated suppression of circadian melatonin production. While LAN is reported to accelerate aging by promoting age-associated carcinogenesis in several animal models, the specific molecular mechanism(s) of its action are not fully understood. Here, we review literature supporting a connection between LAN-induced central circadian disruption of peripheral circadian rhythms and clock function, LINE-1 retrotransposon-associated genomic instability, metabolic deregulation, and aging. We propose that aging is a progressive decline in the stability, continuity, and synchronization of multi-frequency oscillations in biological processes to a temporally disorganized state. By extension, healthy aging is the ability to maintain the most consistent, stable, and entrainable rhythmicity and coordination of these oscillations, at the molecular, cellular, and systemic levels.
authors: Department of Structural and Cellular Biology, Tulane School of Medicine, Tulane University New Orleans, LA, USA ; Tulane Cancer Center, Tulane Center for Aging, and Tulane Center for Circadian Biology New Orleans, LA, USA.
authors: Victoria P
authors: VP
authors: Belancio
authors: Department of Structural and Cellular Biology, Tulane School of Medicine, Tulane University New Orleans, LA, USA ; Tulane Cancer Center, Tulane Center for Aging, and Tulane Center for Circadian Biology New Orleans, LA, USA.
authors: David E
authors: DE
authors: Blask
authors: Tulane Cancer Center, Tulane Center for Aging, and Tulane Center for Circadian Biology New Orleans, LA, USA ; Department of Epidemiology, Tulane University New Orleans, LA, USA.
authors: Prescott
authors: P
authors: Deininger
authors: Department of Structural and Cellular Biology, Tulane School of Medicine, Tulane University New Orleans, LA, USA ; Tulane Cancer Center, Tulane Center for Aging, and Tulane Center for Circadian Biology New Orleans, LA, USA.
authors: Steven M
authors: SM
authors: Hill
authors: Tulane Cancer Center, Tulane Center for Aging, and Tulane Center for Circadian Biology New Orleans, LA, USA ; Department of Medicine, Tulane University New Orleans, LA, USA.
authors: S Michal
authors: SM
authors: Jazwinski
keywords: LINE-1; aging; light exposure at night; metabolism; retroelements
references: Cell. 1996 Nov 29;87(5):905-16
references: 8945517
references: Neuro Endocrinol Lett. 2003 Feb-Apr;24(1-2):33-8
references: 12743529
references: Nat Genet. 2003 Sep;35(1):41-8
references: 12897783
references: Hum Mol Genet. 2011 Sep 1;20(17):3386-400
references: 21636526
references: Cell. 2005 Feb 25;120(4):513-22
references: 15734683
references: Cancer Res. 2009 Dec 15;69(24):9315-22
references: 19934327
references: Nucleic Acids Res. 2007;35(22):7466-74
references: 17913742
references: J Clin Endocrinol Metab. 2001 Jul;86(7):3292-5
references: 11443203
references: Nat Cell Biol. 2004 Feb;6(2):168-70
references: 14755273
references: Comp Med. 2010 Oct;60(5):348-56
references: 21262119
references: Nucleic Acids Res. 2010 Jul;38(12):3909-22
references: 20215437
references: Free Radic Res. 2002 Dec;36(12):1323-9
references: 12607824
references: Aging Cell. 2010 Oct;9(5):698-708
references: 20569235
references: J Pineal Res. 2014 Sep;57(2):228-38
references: 25052362
references: Prog Brain Res. 2010;181:127-51
references: 20478436
references: Mech Ageing Dev. 2005 Jun-Jul;126(6-7):621-8
references: 15888314
references: Cell. 2013 Jun 20;153(7):1448-60
references: 23791176
references: Integr Cancer Ther. 2009 Dec;8(4):337-46
references: 20050373
references: Breast Cancer Res Treat. 2009 Nov;118(2):293-305
references: 18979234
references: Nucleic Acids Res. 2011 Apr;39(8):3176-87
references: 21193487
references: Nature. 2013 Jul 18;499(7458):346-9
references: 23783513
references: Aging Cell. 2013 Apr;12(2):269-79
references: 23425690
references: CA Cancer J Clin. 2014 May-Jun;64(3):207-18
references: 24604162
references: Annu Rev Physiol. 2013;75:645-68
references: 23398157
references: Nucleic Acids Res. 2014 Jul;42(12):7694-707
references: 24914052
references: Nature. 2012 Nov 15;491(7424):348-56
references: 23151577
references: J Circadian Rhythms. 2008 Mar 11;6:4
references: 18334030
references: Mol Biol Cell. 2014 Oct 1;25(19):3081-93
references: 25103245
references: J Biol Rhythms. 2011 Apr;26(2):149-59
references: 21454295
references: PLoS One. 2014 Aug 06;9(8):e102776
references: 25099274
references: Cell. 2014 Jul 31;158(3):659-72
references: 25083875
references: DNA Repair (Amst). 2008 Jun 1;7(6):983-9
references: 18396111
references: Curr Mol Med. 2010 Apr;10(3):321-34
references: 20334625
references: Eur J Cancer. 2005 Sep;41(13):2023-32
references: 16084719
references: Sci Signal. 2014 Sep 09;7(342):re6
references: 25205852
references: Science. 1991 Dec 20;254(5039):1808-10
references: 1722352
references: Genome Res. 2008 Mar;18(3):343-58
references: 18256243
references: Integr Cancer Ther. 2009 Dec;8(4):303-8
references: 20042409
references: Aging (Albany NY). 2009 Oct 02;1(10):855-65
references: 20157558
references: Nucleic Acids Res. 2012 Feb;40(4):1666-83
references: 22053090
references: Cell. 2013 Dec 19;155(7):1464-78
references: 24360271
references: Mech Ageing Dev. 2002 Apr 30;123(8):907-15
references: 12044939
references: Cell. 1996 Nov 29;87(5):917-27
references: 8945518
references: Aging (Albany NY). 2013 Dec;5(12):867-83
references: 24323947
references: J Natl Cancer Inst. 2001 Oct 17;93(20):1563-8
references: 11604480
references: Cell. 2002 Oct 4;111(1):41-50
references: 12372299
references: Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2864-7
references: 19164551
references: Int J Cancer. 2004 Sep 10;111(4):475-9
references: 15239122
references: J Pineal Res. 2009 Oct;47(3):211-20
references: 19627456
references: Annu Rev Physiol. 2010;72:517-49
references: 20148687
references: Cell. 2008 Jul 25;134(2):317-28
references: 18662546
references: Cell Metab. 2010 Nov 3;12(5):509-20
references: 21035761
references: Oncogene. 1992 Mar;7(3):507-10
references: 1312702
references: Proc Natl Acad Sci U S A. 2012 May 1;109 (18):7013-8
references: 22509031
references: Scand J Work Environ Health. 2012 Jul;38(4):380-90
references: 22349009
references: Crit Rev Oncol Hematol. 2003 Mar;45(3):277-304
references: 12633840
references: Biogerontology. 2012 Apr;13(2):119-31
references: 21972126
references: PLoS One. 2012;7(5):e37799
references: 22629458
references: Am J Prev Med. 2013 Sep;45(3):343-6
references: 23953362
references: Cancer Res. 2011 Apr 1;71(7):2622-31
references: 21310824
references: Breast Cancer Res Treat. 2011 May;127(1):91-8
references: 20549340
references: Science. 1980 Dec 12;210(4475):1267-9
references: 7434030
references: J Biol Rhythms. 2009 Jun;24(3):193-202
references: 19465696
references: Cancer. 1994 May 1;73(9):2333-6
references: 8168038
references: Proc Natl Acad Sci U S A. 2012 Nov 20;109(47):19392-6
references: 23129611
references: Science. 2012 Aug 24;337(6097):967-71
references: 22745252
references: J Mol Biol. 2006 Apr 14;357(5):1383-93
references: 16490214
references: Curr Aging Sci. 2010 Feb;3(1):3-19
references: 20298165
references: Science. 2014 Aug 1;345(6196):1251343
references: 25082706
references: J Pineal Res. 2010 Jan;48(1):9-19
references: 20025641
references: J Mol Biol. 2002 Feb 22;316(3):459-73
references: 11866511
references: Semin Cancer Biol. 2010 Aug;20(4):200-10
references: 20600922
references: Bioinformatics. 2014 Dec 15;30(24):3558-60
references: 25172923
references: J Cell Sci. 2010 Nov 15;123(Pt 22):3837-48
references: 21048160
references: Ecol Evol. 2014 Sep;4(17):3494-507
references: 25535564
references: Genome Res. 2012 Dec;22(12):2328-38
references: 22968929
references: Mech Ageing Dev. 2007 Jan;128(1):36-44
references: 17116315
references: Sci STKE. 2001 Nov 06;2001(107):pe39
references: 11698691
references: Chronobiol Int. 2012 May;29(4):415-29
references: 22489607
references: Cancer Res. 2005 Dec 1;65(23):11174-84
references: 16322268
references: J Natl Cancer Inst. 2001 Oct 17;93(20):1557-62
references: 11604479
references: J Pineal Res. 2011 Oct;51(3):259-69
references: 21605163
references: Rejuvenation Res. 2008 Apr;11(2):467-71
references: 18321196
references: Cell. 2012 Oct 26;151(3):483-96
references: 23101622
references: Nucleic Acids Res. 2014;42(16):10488-502
references: 25143528
references: Nature. 2001 Feb 15;409(6822):860-921
references: 11237011