REVIEW

Physiological links of circadian clock and biological clock of aging

  • Fang Liu 1,2 ,
  • Hung-Chun Chang , 1
Expand
  • 1. Institute of Neuroscience, State Key Laboratory of Neuroscience, Key Laboratory of Primate Neurobiology, CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China
  • 2. University of Chinese Academy of Sciences, Shanghai 200031, China

Received date: 22 Nov 2016

Accepted date: 20 Dec 2016

Published date: 23 Aug 2017

Copyright

2017 The Author(s) 2017. This article is published with open access at Springerlink.com and journal.hep.com.cn

Abstract

Circadian rhythms orchestrate biochemical and physiological processes in living organisms to respond the day/night cycle. In mammals, nearly all cells hold selfsustained circadian clocks meanwhile couple the intrinsic rhythms to systemic changes in a hierarchical manner. The suprachiasmatic nucleus (SCN) of the hypothalamus functions as the master pacemaker to initiate daily synchronization according to the photoperiod, in turn determines the phase of peripheral cellular clocks through a variety of signaling relays, including endocrine rhythms and metabolic cycles. With aging, circadian desynchrony occurs at the expense of peripheral metabolic pathologies and central neurodegenerative disorders with sleep symptoms, and genetic ablation of circadian genes in model organisms resembled the aging-related features. Notably, a number of studies have linked longevity nutrient sensing pathways in modulating circadian clocks. Therapeutic strategies that bridge the nutrient sensing pathways and circadian clock might be rational designs to defy aging.

Cite this article

Fang Liu , Hung-Chun Chang . Physiological links of circadian clock and biological clock of aging[J]. Protein & Cell, 2017 , 8(7) : 477 -488 . DOI: 10.1007/s13238-016-0366-2

1
AbrahamsonEE, MooreRY (2001) Suprachiasmatic nucleus in the mouse: retinal innervation, intrinsic organization and efferent projections. Brain Res916:172–191

DOI

2
AbrahamsonEE, LeakRK, MooreRY (2001) The suprachiasmatic nucleus projects to posterior hypothalamic arousal systems. NeuroReport12:435–440

DOI

3
AdamovichY, LadeuixB, GolikM, KoenersMP, AsherG (2017) Rhythmic oxygen levels reset circadian clocks through HIF1alpha. Cell Metab. doi:10.1016/j.cmet.2016.09.014

DOI

4
AidaR, MoriyaT, ArakiM, AkiyamaM, WadaK, WadaE, ShibataS (2002) Gastrin-releasing peptide mediates photic entrainable signals to dorsal subsets of suprachiasmatic nucleus via induction of period gene in mice. Mol Pharmacol61:26–34

DOI

5
AntleMC, SilverR (2005) Orchestrating time: arrangements of the brain circadian clock. Trends Neurosci28:145–151

DOI

6
AntochMP, GorbachevaVY, VykhovanetsO, ToshkovIA, KondratovRV, KondratovaAA, LeeC, NikitinAY (2008) Disruption of the circadian clock due to the clock mutation has discrete effects on aging and carcinogenesis. Cell Cycle7:1197–1204

DOI

7
ArnulfI, NielsenJ, LohmannE, SchieferJ, WildE, JennumP, KonofalE, WalkerM, OudietteD, TabriziS (2008) Rapid eye movement sleep disturbances in Huntington disease. Arch Neurol65:482–488

DOI

8
AsherG, Sassone-CorsiP (2015) Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock. Cell161:84–92

DOI

9
AsherG, GatfieldD, StratmannM, ReinkeH, DibnerC, KreppelF, MostoslavskyR, AltFW, SchiblerU (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell134:317–328

DOI

10
Aston-JonesG, ChenS, ZhuY, OshinskyML (2001) A neural circuit for circadian regulation of arousal. Nat Neurosci4:732–738

DOI

11
AzizA, FronczekR, Maat-SchiemanM, UnmehopaU, RoelandseF, OvereemS, van DuinenS, LammersGJ, SwaabD, RoosR (2008) Hypocretin and melanin-concentrating hormone in patients with Huntington disease. Brain Pathol18:474–483

DOI

12
BaroneP, AntoniniA, ColosimoC, MarconiR, MorganteL, AvarelloTP, BottacchiE, CannasA, CeravoloG, CeravoloR (2009) The PRIAMO study: a multicenter assessment of nonmotor symptoms and their impact on quality of life in Parkinson’s disease. Mov Dis24:1641–1649

DOI

13
BarzilaiN, CrandallJP, KritchevskySB, EspelandMA (2016) Metformin as a tool to target aging. Cell Metab23:1060–1065

DOI

14
BassJ, TakahashiJS (2010) Circadian integration of metabolism and energetics. Science330:1349–1354

DOI

15
BollingerT, SchiblerU (2014) Circadian rhythms—from genes to physiology and disease. Swiss Med Wkly144:w13984

DOI

16
BonkowskiMS, SinclairDA (2016) Slowing ageing by design: the rise of NAD+ and sirtuin-activating compounds. Nat Rev Mol Cell Biol17:679–690

DOI

17
BraakH, GhebremedhinE, RubU, BratzkeH, Del TrediciK (2004) Stages in the development of Parkinson’s disease-related pathology. Cell Tissue Res318:121–134

DOI

18
BrayMS, YoungME (2007) Circadian rhythms in the development of obesity: potential role for the circadian clock within the adipocyte. Obes Rev8:169–181

DOI

19
BreenDP, VuonoR, NawarathnaU, FisherK, ShneersonJM, ReddyAB, BarkerRA (2014) Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol71:589–595

DOI

20
CaiY, LiuS, SothernRB, XuS, ChanP (2010) Expression of clock genes Per1 and Bmal1 in total leukocytes in health and Parkinson’s disease. Eur J Neurol17:550–554

DOI

21
CaoR, RobinsonB, XuH, GkogkasC, KhoutorskyA, AlainT, YanagiyaA, NevarkoT, LiuAC, AmirS (2013) Translational control of entrainment and synchrony of the suprachiasmatic circadian clock by mTOR/4E-BP1 signaling. Neuron79:712–724

DOI

22
ChangHC, GuarenteL (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell153:1448–1460

DOI

23
ChangHC, GuarenteL (2014) SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab25:138–145

DOI

24
ChawlaA, LazarMA (1993) Induction of Rev-ErbA alpha, an orphan receptor encoded on the opposite strand of the alpha-thyroid hormone receptor gene, during adipocyte differentiation. J Biol Chem268:16265–16269

25
ChoH, ZhaoX, HatoriM, YuRT, BarishGD, LamMT, ChongLW, DiTacchioL, AtkinsAR, GlassCK (2012) Regulation of circadian behaviour and metabolism by REV-ERB-alpha and REV-ERB-beta. Nature485:123–127

DOI

26
ChoiHJ, LeeCJ, SchroederA, KimYS, JungSH, KimJS, KimDY, SonEJ, HanHC, HongSK (2008) Excitatory actions of GABA in the suprachiasmatic nucleus. J Neurosci28:5450–5459

DOI

27
ChouTC, BjorkumAA, GausSE, LuJ, ScammellTE, SaperCB (2002) Afferents to the ventrolateral preoptic nucleus. J Neurosci22:977–990

28
ChouTC, ScammellTE, GooleyJJ, GausSE, SaperCB, LuJ (2003) Critical role of dorsomedial hypothalamic nucleus in a wide range of behavioral circadian rhythms. J Neurosci23:10691–10702

29
ChoudharyC, WeinertBT, NishidaY, VerdinE, MannM (2014) The growing landscape of lysine acetylation links metabolism and cell signalling. Nat Rev Mol Cell Biol15:536–550

DOI

30
ColmanRJ, AndersonRM, JohnsonSC, KastmanEK, KosmatkaKJ, BeasleyTM, AllisonDB, CruzenC, SimmonsHA, KemnitzJW (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science325:201–204

DOI

31
ColmanRJ, BeasleyTM, KemnitzJW, JohnsonSC, WeindruchR, AndersonRM (2014) Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat Commun5:3557

DOI

32
ColwellCS (2011) Linking neural activity and molecular oscillations in the SCN. Nat Rev Neurosci12:553–569

DOI

33
DavidsonAJ, StraumeM, BlockGD, MenakerM (2006) Daily timed meals dissociate circadian rhythms in hepatoma and healthy host liver. Int J Cancer118:1623–1627

DOI

34
De JeuM, PennartzC (2002) Circadian modulation of GABA function in the rat suprachiasmatic nucleus: excitatory effects during the night phase. J Neurophysiol87:834–844

DOI

35
DibnerC, SchiblerU, AlbrechtU (2010) The mammalian circadian timing system: organization and coordination of central and peripheral clocks. Annu Rev Physiol72:517–549

DOI

36
DubrovskyYV, SamsaWE, KondratovRV (2010) Deficiency of circadian protein CLOCK reduces lifespan and increases agerelated cataract development in mice. Aging2:936–944

DOI

37
DuffyJF, CzeislerCA (2002) Age-related change in the relationship between circadian period, circadian phase, and diurnal preference in humans. Neurosci Lett318:117–120

DOI

38
Eckel-MahanKL, PatelVR, de MateoS, Orozco-SolisR, CegliaNJ, SaharS, Dilag-PenillaSA, DyarKA, BaldiP, Sassone-CorsiP (2013) Reprogramming of the circadian clock by nutritional challenge. Cell155:1464–1478

DOI

39
EverettLJ, LazarMA (2014) Nuclear receptor Rev-erbalpha: up, down, and all around. Trends Endocrinol Metab25:586–592

DOI

40
FahrenkrugJ, PopovicN, GeorgB, BrundinP, HannibalJ (2007) Decreased VIP and VPAC2 receptor expression in the biological clock of the R6/2 Huntington’s disease mouse. J Mol Neurosci31:139–148

41
FarajniaS, MichelS, DeboerT, vanderLeestHT, HoubenT, RohlingJH, RamkisoensingA, YasenkovR, MeijerJH (2012) Evidence for neuronal desynchrony in the aged suprachiasmatic nucleus clock. J Neurosci32:5891–5899

DOI

42
FifelK, CooperHM (2014) Loss of dopamine disrupts circadian rhythms in a mouse model of Parkinson’s disease. Neurobiol Dis71:359–369

DOI

43
FilipskiE, KingVM, LiX, GrandaTG, MormontMC, ClaustratB, HastingsMH, LeviF (2003) Disruption of circadian coordination accelerates malignant growth in mice. Pathol Biol51:216–219

DOI

44
FontanaL, PartridgeL (2015) Promoting health and longevity through diet: from model organisms to humans. Cell161:106–118

DOI

45
FronczekR, OvereemS, LeeSY, HegemanIM, van PeltJ, van DuinenSG, LammersGJ, SwaabDF (2007) Hypocretin (orexin) loss in Parkinson’s disease. Brain130:1577–1585

DOI

46
FroyO (2013) Circadian aspects of energy metabolism and aging. Ageing Res Rev12:931–940

DOI

47
FuL, PelicanoH, LiuJ, HuangP, LeeC (2002) The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell111:41–50

DOI

48
GaberyS, MurphyK, SchultzK, LoyCT, McCuskerE, KirikD, HallidayG, PetersenA (2010) Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses. Acta Neuropathol120:777–788

DOI

49
GibsonEM, WilliamsWP 3rd, KriegsfeldLJ (2009) Aging in the circadian system: considerations for health, disease prevention and longevity. Exp Gerontol44:51–56

DOI

50
GolombekDA, RosensteinRE (2010) Physiology of circadian entrainment. Physiol Rev90:1063–1102

DOI

51
GomesAP, PriceNL, LingAJ, MoslehiJJ, MontgomeryMK, RajmanL, WhiteJP, TeodoroJS, WrannCD, HubbardBP (2013) Declining NAD(+) induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell155:1624–1638

DOI

52
GoodmanAO, BarkerRA (2010) How vital is sleep in Huntington’s disease?J Neurol257:882–897

DOI

53
GuarenteL (2013) Calorie restriction and sirtuins revisited. Genes Dev27:2072–2085

DOI

54
HamadaT, AntleMC, SilverR (2004) Temporal and spatial expression patterns of canonical clock genes and clock-controlled genes in the suprachiasmatic nucleus. Eur J Neurosci19:1741–1748

DOI

55
HarrisonDE, StrongR, SharpZD, NelsonJF, AstleCM, FlurkeyK, NadonNL, WilkinsonJE, FrenkelK, CarterCS (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature460:392–395

DOI

56
HerskovitsAZ, GuarenteL (2014) SIRT1 in neurodevelopment and brain senescence. Neuron81:471–483

DOI

57
HirayamaJ, SaharS, GrimaldiB, TamaruT, TakamatsuK, NakahataY, Sassone-CorsiP (2007) CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature450:1086–1090

DOI

58
HofmanMA, SwaabDF (1994) Alterations in circadian rhythmicity of the vasopressin-producing neurons of the human suprachiasmatic nucleus (SCN) with aging. Brain Res651:134–142

DOI

59
HofmanMA, SwaabDF (1995) Influence of aging on the seasonal rhythm of the vasopressin-expressing neurons in the human suprachiasmatic nucleus. Neurobiol Aging16:965–971

DOI

60
HofmanMA, SwaabDF (2006) Living by the clock: the circadian pacemaker in older people. Ageing Res Rev5:33–51

DOI

61
HofmanMA, ZhouJN, SwaabDF (1996) No evidence for a diurnal vasoactive intestinal polypeptide (VIP) rhythm in the human suprachiasmatic nucleus. Brain Res722:78–82

DOI

62
HosodaH, KatoK, AsanoH, ItoM, KatoH, IwamotoT, SuzukiA, MasushigeS, KidaS (2009) CBP/p300 is a cell type-specific modulator of CLOCK/BMAL1-mediated transcription. Mol Brain2:34

DOI

63
HurdMW, RalphMR (1998) The significance of circadian organization for longevity in the golden hamster. J Biol Rhythms13:430–436

DOI

64
IranzoA (2013) Parkinson disease and sleep: sleep-wake changes in the premotor stage of Parkinson disease; impaired olfaction and other prodromal features. Curr Neurol Neurosci Rep13:373

DOI

65
Jung-HynesB, ReiterRJ, AhmadN (2010) Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer. J Pineal Res48:9–19

DOI

66
KaeberleinM, RabinovitchPS, MartinGM (2015) Healthy aging: the ultimate preventative medicine. Science350:1191–1193

DOI

67
KalsbeekA, PalmIF, La FleurSE, ScheerFA, Perreau-LenzS, RuiterM, KreierF, CailottoC, BuijsRM (2006) SCN outputs and the hypothalamic balance of life. J Biol Rhythms21:458–469

DOI

68
KhapreRV, KondratovaAA, PatelS, DubrovskyY, WrobelM, AntochMP, KondratovRV (2014) BMAL1-dependent regulation of the mTOR signaling pathway delays aging. Aging6:48–57

DOI

69
KolkerDE, FukuyamaH, HuangDS, TakahashiJS, HortonTH, TurekFW (2003) Aging alters circadian and light-induced expression of clock genes in golden hamsters. J Biol Rhythms18:159–169

DOI

70
KondratovRV, KondratovaAA, GorbachevaVY, VykhovanetsOV, AntochMP (2006) Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev20:1868–1873

DOI

71
KondratovaAA, KondratovRV (2012) The circadian clock and pathology of the ageing brain. Nat Rev Neurosci13:325–335

DOI

72
KudoT, LohDH, TruongD, WuY, ColwellCS (2011) Circadian dysfunction in a mouse model of Parkinson’s disease. Exp Neurol232:66–75

DOI

73
LamiaKA, SachdevaUM, DiTacchioL, WilliamsEC, AlvarezJG, EganDF, VasquezDS, JuguilonH, PandaS, ShawRJ (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science326:437–440

DOI

74
Lande-DinerL, BoyaultC, KimJY, WeitzCJ (2013) A positive feedback loop links circadian clock factor CLOCK-BMAL1 to the basic transcriptional machinery. Proc Natl Acad Sci USA110:16021–16026

DOI

75
LeeCC (2005) The circadian clock and tumor suppression by mammalian period genes. Methods Enzymol393:852–861

DOI

76
LeeC, EtchegarayJP, CagampangFR, LoudonAS, ReppertSM (2001) Posttranslational mechanisms regulate the mammalian circadian clock. Cell107:855–867

DOI

77
LeeJH, BliwiseDL, AnsariFP, GoldsteinFC, CellarJS, LahJJ, LeveyAI (2007) Daytime sleepiness and functional impairment in Alzheimer disease. Am J Geriatr Psychiatry15:620–626

DOI

78
LiH, SatinoffE (1998) Fetal tissue containing the suprachiasmatic nucleus restores multiple circadian rhythms in old rats. Am J Physiol275:R1735–R1744

79
LiXM, DelaunayF, DulongS, ClaustratB, ZamperaS, FujiiY, TeboulM, BeauJ, LeviF (2010) Cancer inhibition through circadian reprogramming of tumor transcriptome with meal timing. Cancer Res70:3351–3360

DOI

80
LiJ, KimSG, BlenisJ (2014) Rapamycin: one drug, many effects. Cell Metab19:373–379

DOI

81
LiptonJO, YuanED, BoyleLM, Ebrahimi-FakhariD, KwiatkowskiE, NathanA, GuttlerT, DavisF, AsaraJM, SahinM (2015) The circadian protein BMAL1 regulates translation in response to S6K1-mediated phosphorylation. Cell161:1138–1151

DOI

82
LopezM, NogueirasR, Tena-SempereM, DieguezC (2016) Hypothalamic AMPK: a canonical regulator of whole-body energy balance. Nat Rev Endocrinol12:421–432

DOI

83
Lopez-OtinC, BlascoMA, PartridgeL, SerranoM, KroemerG (2013) The hallmarks of aging. Cell153:1194–1217

DOI

84
Lopez-OtinC, GalluzziL, FreijeJM, MadeoF, KroemerG (2016) Metabolic control of longevity. Cell166:802–821

DOI

85
MarchevaB, RamseyKM, BuhrED, KobayashiY, SuH, KoCH, IvanovaG, OmuraC, MoS, VitaternaMH (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature466:627–631

DOI

86
MasriS, RigorP, CervantesM, CegliaN, SebastianC, XiaoCY, Roqueta-RiveraM, DengCX, OsborneTF, MostoslavskyR (2014) Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell158:659–672

DOI

87
MattisJ, SehgalA (2016) Circadian rhythms, sleep, and disorders of aging. Trends Endocrinol Metab27:192–203

DOI

88
Meyer-SpascheA, ReedHE, PigginsHD (2002) Neurotensin phaseshifts the firing rate rhythm of neurons in the rat suprachiasmatic nuclei in vitro. Eur J Neurosci16:339–344

DOI

89
MooreRY, SpehJC (1993) GABA is the principal neurotransmitter of the circadian system. Neurosci Lett150:112–116

DOI

90
MorinLP, AllenCN (2006) The circadian visual system, 2005. Brain Res Rev51:1–60

DOI

91
MorinLP, ShiversKY, BlanchardJH, MuscatL (2006) Complex organization of mouse and rat suprachiasmatic nucleus. Neuroscience137:1285–1297

DOI

92
MortonAJ, WoodNI, HastingsMH, HurelbrinkC, BarkerRA, MaywoodES (2005) Disintegration of the sleep-wake cycle and circadian timing in Huntington’s disease. J Neurosci25:157–163

DOI

93
NadonNL (2006) Exploiting the rodent model for studies on the pharmacology of lifespan extension. Aging Cell5:9–15

DOI

94
NakahataY, KaluzovaM, GrimaldiB, SaharS, HirayamaJ, ChenD, GuarenteLP, Sassone-CorsiP (2008) The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell134:329–340

DOI

95
NakahataY, SaharS, AstaritaG, KaluzovaM, Sassone-CorsiP (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science324:654–657

DOI

96
NakamuraW, YamazakiS, TakasuNN, MishimaK, BlockGD (2005) Differential response of Period 1 expression within the suprachiasmatic nucleus. J Neurosci25:5481–5487

DOI

97
NakamuraTJ, NakamuraW, YamazakiS, KudoT, CutlerT, ColwellCS, BlockGD (2011) Age-related decline in circadian output. J Neurosci31:10201–10205

DOI

98
NovakCM, NunezAA (2000) A sparse projection from the suprachiasmatic nucleus to the sleep active ventrolateral preoptic area in the rat. NeuroReport11:93–96

DOI

99
OzturkN, LeeJH, GaddameedhiS, SancarA (2009) Loss of cryptochrome reduces cancer risk in p53 mutant mice. Proc Natl Acad Sci USA106:2841–2846

DOI

100
PandaS, HogeneschJB, KaySA (2002) Circadian rhythms from flies to human. Nature417:329–335

DOI

101
PeekCB, LevineDC, CedernaesJ, TaguchiA, KobayashiY, TsaiSJ, BonarNA, McNultyMR, RamseyKM, BassJ (2017) Circadian clock interaction with HIF1alpha mediates oxygenic metabolism and anaerobic glycolysis in skeletal muscle. Cell Metab. doi:10.1016/j.cmet.2016.09.010

DOI

102
PenevPD, KolkerDE, ZeePC, TurekFW (1998) Chronic circadian desynchronization decreases the survival of animals with cardiomyopathic heart disease. Am J Physiol275:H2334–H2337

103
PreitnerN, DamiolaF, Lopez-MolinaL, ZakanyJ, DubouleD, AlbrechtU, SchiblerU (2002) The orphan nuclear receptor REVERBalpha controls circadian transcription within the positive limb of the mammalian circadian oscillator. Cell110:251–260

DOI

104
PulivarthySR, TanakaN, WelshDK, De HaroL, VermaIM, PandaS (2007) Reciprocity between phase shifts and amplitude changes in the mammalian circadian clock. Proc Natl Acad Sci USA104:20356–20361

DOI

105
PuramRV, KowalczykMS, de BoerCG, SchneiderRK, MillerPG, McConkeyM, TothovaZ, TejeroH, HecklD, JarasM (2016) Core circadian clock genes regulate leukemia stem cells in AML. Cell165:303–316

DOI

106
QuZ, ZhangH, HuangM, ShiG, LiuZ, XieP, LiH, WangW, XuG, ZhangY (2016) Loss of ZBTB20 impairs circadian output and leads to unimodal behavioral rhythms. eLife5:e17171

DOI

107
RamadoriG, FujikawaT, FukudaM, AndersonJ, MorganDA, MostoslavskyR, StuartRC, PerelloM, ViannaCR, NillniEA (2010) SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity. Cell Metab12:78–87

DOI

108
RamadoriG, FujikawaT, AndersonJ, BerglundED, FrazaoR, MichanS, ViannaCR, SinclairDA, EliasCF, CoppariR (2011) SIRT1 deacetylase in SF1 neurons protects against metabolic imbalance. Cell Metab14:301–312

DOI

109
RamseyKM, YoshinoJ, BraceCS, AbrassartD, KobayashiY, MarchevaB, HongHK, ChongJL, BuhrED, LeeC (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science324:651–654

DOI

110
ReddyAB, ReyG (2014) Metabolic and nontranscriptional circadian clocks: eukaryotes. Annu Rev Biochem83:165–189

DOI

111
ReppertSM, WeaverDR (2002) Coordination of circadian timing in mammals. Nature418:935–941

DOI

112
RieraCE, DillinA (2015) Tipping the metabolic scales towards increased longevity in mammals. Nat Cell Biol17:196–203

DOI

113
RoozendaalB, van GoolWA, SwaabDF, HoogendijkJE, MirmiranM (1987) Changes in vasopressin cells of the rat suprachiasmatic nucleus with aging. Brain Res409:259–264

DOI

114
RudicRD, McNamaraP, CurtisAM, BostonRC, PandaS, HogeneschJB, FitzgeraldGA (2004) BMAL1 and CLOCK, two essential components of the circadian clock, are involved in glucose homeostasis. PLoS Biol2:e377

DOI

115
SaharS, Sassone-CorsiP (2009) Metabolism and cancer: the circadian clock connection. Nat Rev Cancer9:886–896

DOI

116
SatlinA, VolicerL, StopaEG, HarperD (1995) Circadian locomotor activity and core-body temperature rhythms in Alzheimer’s disease. Neurobiol Aging16:765–771

DOI

117
SatoTK, PandaS, MiragliaLJ, ReyesTM, RudicRD, McNamaraP, NaikKA, FitzGeraldGA, KaySA, HogeneschJB (2004) A functional genomics strategy reveals Rora as a component of the mammalian circadian clock. Neuron43:527–537

DOI

118
SatohA, BraceCS, RensingN, CliftenP, WozniakDF, HerzogED, YamadaKA, ImaiS (2013) Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab18:416–430

DOI

119
ScarbroughK, Losee-OlsonS, WallenEP, TurekFW (1997) Aging and photoperiod affect entrainment and quantitative aspects of locomotor behavior in Syrian hamsters. Am J Physiol272: R1219–R1225

120
ShimbaS, IshiiN, OhtaY, OhnoT, WatabeY, HayashiM, WadaT, AoyagiT, TezukaM (2005) Brain and muscle Arnt-like protein-1 (BMAL1), a component of the molecular clock, regulates adipogenesis. Proc Natl Acad Sci USA102:12071–12076

DOI

121
ShinoharaK, HirumaH, FunabashiT, KimuraF (2000) GABAergic modulation of gap junction communication in slice cultures of the rat suprachiasmatic nucleus. Neuroscience96:591–596

DOI

122
SoltLA, WangY, BanerjeeS, HughesT, KojetinDJ, LundasenT, ShinY, LiuJ, CameronMD, NoelR (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature485:62–68

DOI

123
StashiE, LanzRB, MaoJ, MichailidisG, ZhuB, KettnerNM, PutluriN, ReinekeEL, ReinekeLC, DasguptaS (2014) SRC-2 is an essential coactivator for orchestrating metabolism and circadian rhythm. Cell reports6:633–645

DOI

124
SterniczukR, AntleMC, LaferlaFM, DyckRH (2010a) Characterization of the 3xTg-AD mouse model of Alzheimer’s disease: part 2. Behavioral and cognitive changes. Brain Res1348:149–155

DOI

125
SterniczukR, DyckRH, LaferlaFM, AntleMC (2010b) Characterization of the 3xTg-AD mouse model of Alzheimer’s disease: part 1. Circadian changes. Brain Res1348:139–148

DOI

126
SwaabDF, FliersE, PartimanTS (1985) The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res342:37–44

DOI

127
TorraIP, TsibulskyV, DelaunayF, SaladinR, LaudetV, FruchartJC, KosykhV, StaelsB (2000) Circadian and glucocorticoid regulation of Rev-erbalpha expression in liver. Endocrinology141:3799–3806

DOI

128
TurekFW, JoshuC, KohsakaA, LinE, IvanovaG, McDearmonE, LaposkyA, Losee-OlsonS, EastonA, JensenDR (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science308:1043–1045

DOI

129
UmJH, YangS, YamazakiS, KangH, ViolletB, ForetzM, ChungJH (2007) Activation of 5’-AMP-activated kinase with diabetes drug metformin induces casein kinase Iepsilon (CKIepsilon)-dependent degradation of clock protein mPer2. J Biol Chem282:20794–20798

DOI

130
ValentinuzziVS, ScarbroughK, TakahashiJS, TurekFW (1997) Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice. Am J Physiol273:R1957–R1964

131
van SomerenEJ, HagebeukEE, LijzengaC, ScheltensP, de RooijSE, JonkerC, PotAM, MirmiranM, SwaabDF (1996) Circadian rest-activity rhythm disturbances in Alzheimer’s disease. Biol Psychiatry40:259–270

DOI

132
VidenovicA, LazarAS, BarkerRA, OvereemS (2014) ‘The clocks that time us’–circadian rhythms in neurodegenerative disorders. Nat Rev Neurol10:683–693

DOI

133
WeinertD (2000) Age-dependent changes of the circadian system. Chronobiol Int17:261–283

DOI

134
WelshDK, TakahashiJS, KaySA (2010) Suprachiasmatic nucleus: cell autonomy and network properties. Annu Rev Physiol72:551–577

DOI

135
WoodJG, RoginaB, LavuS, HowitzK, HelfandSL, TatarM, SinclairD (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature430:686–689

DOI

136
WuY, TangD, LiuN, XiongW, HuangH, LiY, MaZ, ZhaoH, ChenP, QiX (2017) Reciprocal regulation between the circadian clock and hypoxia signaling at the genome level in mammals. Cell Metab. doi:10.1016/j.cmet.2016.09.009

DOI

137
WyseCA, CooganAN (2010) Impact of aging on diurnal expression patterns of CLOCK and BMAL1 in the mouse brain. Brain Res1337:21–31

DOI

138
YamazakiS, StraumeM, TeiH, SakakiY, MenakerM, BlockGD (2002) Effects of aging on central and peripheral mammalian clocks. Proc Natl Acad Sci USA99:10801–10806

DOI

139
YanL, OkamuraH (2002) Gradients in the circadian expression of Per1 and Per2 genes in the rat suprachiasmatic nucleus. Eur J Neurosci15:1153–1162

DOI

140
YanL, KaratsoreosI, LesauterJ, WelshDK, KayS, FoleyD, SilverR (2007) Exploring spatiotemporal organization of SCN circuits. Cold Spring Harb Symp Quant Biol72:527–541

DOI

141
YoonIY, KripkeDF, ElliottJA, YoungstedtSD, RexKM, HaugerRL (2003) Age-related changes of circadian rhythms and sleep-wake cycles. J Am Geriatr Soc51:1085–1091

DOI

142
ZhangEE, LiuY, DentinR, PongsawakulPY, LiuAC, HirotaT, NusinowDA, SunX, LandaisS, KodamaY (2010) Cryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis. Nat Med16:1152–1156

DOI

143
ZhouJN, HofmanMA, SwaabDF (1995) VIP neurons in the human SCN in relation to sex, age, and Alzheimer’s disease. Neurobiol Aging16:571–576

DOI

Outlines

/