Advertisement

Developing Circadian Therapeutics Against Age-Related Metabolic Decline

  • Kazunari Nohara
  • Seung-Hee Yoo
  • Zheng Chen
Chapter
Part of the Healthy Ageing and Longevity book series (HAL, volume 7)

Abstract

Aging is characterized by a progressive decline in metabolism and physiology throughout the body, and the complex physiological basis is not fully understood. A key intrinsic mechanism to safeguard our physiological well-being is the circadian clock, the biological timer that coordinates diverse essential processes. Epidemiological and genetic studies in the past two decades have established a crucial role of the clock system in metabolic homeostasis and physiological health. Accumulating evidence also points to a functional link between clock decline (e.g., amplitude dampening) and metabolic aging. In this chapter, we review a close relationship among energy homeostasis, aging and the circadian clock. We also describe the current efforts to identify novel small-molecule therapeutics that enhance circadian and metabolic functions. Given that a weakened clock is in part responsible for the metabolic deterioration during aging, such circadian-based therapeutics could be exploited to decelerate metabolic decline and ultimately promote healthy aging.

Keywords

Circadian clock Age-related metabolic decline Small molecules Circadian amplitude Mitochondria 

Notes

Acknowledgements

This work was in part supported by the Robert A. Welch Foundation (AU-1731) and NIH/NIA (R01 AG045828) to Z.C., and NIH/NIGMS (R01 GM114424) to S.-H.Y.

Conflict of Interest

The authors declare no conflict of interest.

References

  1. Agil A, Rosado I, Ruiz R, Figueroa A, Zen N, Fernandez-Vazquez G (2012) Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats. J Pineal Res 52(2):203–210PubMedCrossRefGoogle Scholar
  2. Amara CE, Shankland EG, Jubrias SA, Marcinek DJ, Kushmerick MJ, Conley KE (2007) Mild mitochondrial uncoupling impacts cellular aging in human muscles in vivo. Proc Natl Acad Sci U S A 104(3):1057–1062PubMedPubMedCentralCrossRefGoogle Scholar
  3. Andrews JL, Zhang X, McCarthy JJ, McDearmon EL, Hornberger TA, Russell B, Campbell KS, Arbogast S, Reid MB, Walker JR et al (2010) CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function. Proc Natl Acad Sci U S A 107(44):19090–19095PubMedPubMedCentralCrossRefGoogle Scholar
  4. Antoch MP, Kondratov RV (2013) Pharmacological modulators of the circadian clock as potential therapeutic drugs: focus on genotoxic/anticancer therapy. Handb Exp Pharmacol 217:289–309CrossRefGoogle Scholar
  5. Arble DM, Bass J, Laposky AD, Vitaterna MH, Turek FW (2009) Circadian timing of food intake contributes to weight gain. Obesity (Silver Spring) 17(11):2100–2102CrossRefGoogle Scholar
  6. Arble DM, Vitaterna MH, Turek FW (2011) Rhythmic leptin is required for weight gain from circadian desynchronized feeding in the mouse. PLoS ONE 6(9):e25079PubMedPubMedCentralCrossRefGoogle Scholar
  7. Arendt J (2000) Melatonin, circadian rhythms, and sleep. N Engl J Med 343(15):1114–1116PubMedCrossRefGoogle Scholar
  8. Arendt J (2010) Shift work: coping with the biological clock. Occup Med (Lond) 60(1):10–20CrossRefGoogle Scholar
  9. Asher G, Sassone-Corsi P (2015) Time for food: the intimate interplay between nutrition, metabolism, and the circadian clock. Cell 161(1):84–92PubMedCrossRefGoogle Scholar
  10. Asher G, Schibler U (2011) Crosstalk between components of circadian and metabolic cycles in mammals. Cell Metab 13(2):125–137PubMedCrossRefGoogle Scholar
  11. Asher G, Gatfield D, Stratmann M, Reinke H, Dibner C, Kreppel F, Mostoslavsky R, Alt FW, Schibler U (2008) SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 134(2):317–328PubMedCrossRefGoogle Scholar
  12. Aviram R, Manella G, Kopelman N, Neufeld-Cohen A, Zwighaft Z, Elimelech M, Adamovich Y, Golik M, Wang C, Han X et al (2016) Lipidomics analyses reveal temporal and spatial lipid organization and uncover daily oscillations in intracellular organelles. Mol Cell 62(4):636–648PubMedCrossRefGoogle Scholar
  13. Axelrod J, Wurtman RJ, Winget CM (1964) Melatonin synthesis in the hen pineal gland and its control by light. Nature 201:1134PubMedCrossRefGoogle Scholar
  14. Balaban RS, Nemoto S, Finkel T (2005) Mitochondria, oxidants, and aging. Cell 120(4):483–495PubMedCrossRefGoogle Scholar
  15. Balsalobre A, Damiola F, Schibler U (1998) A serum shock induces circadian gene expression in mammalian tissue culture cells. Cell 93(6):929–937PubMedCrossRefGoogle Scholar
  16. Banerjee S, Wang Y, Solt LA, Griffett K, Kazantzis M, Amador A, El-Gendy BM, Huitron-Resendiz S, Roberts AJ, Shin Y et al (2014) Pharmacological targeting of the mammalian clock regulates sleep architecture and emotional behaviour. Nat Commun 5:5759PubMedPubMedCentralCrossRefGoogle Scholar
  17. Banks G, Nolan PM, Peirson SN (2016) Reciprocal interactions between circadian clocks and aging. Mamm Genome 27(7–8):332–340PubMedPubMedCentralCrossRefGoogle Scholar
  18. Bass J (2012) Circadian topology of metabolism. Nature 491(7424):348–356PubMedCrossRefGoogle Scholar
  19. Bass J (2016) Targeting time in metabolic therapeutics. Cell Metab 23(4):575–577PubMedCrossRefGoogle Scholar
  20. Bass J, Takahashi JS (2010) Circadian integration of metabolism and energetics. Science 330(6009):1349–1354PubMedPubMedCentralCrossRefGoogle Scholar
  21. Belancio VP, Blask DE, Deininger P, Hill SM, Jazwinski SM (2014) The aging clock and circadian control of metabolism and genome stability. Front Genet 5:455PubMedGoogle Scholar
  22. Benloucif S, Burgess HJ, Klerman EB, Lewy AJ, Middleton B, Murphy PJ, Parry BL, Revell VL (2008) Measuring melatonin in humans. J Clin Sleep Med 4(1):66–69PubMedPubMedCentralGoogle Scholar
  23. Bertolotti M, Gabbi C, Anzivino C, Crestani M, Mitro N, Del Puppo M, Godio C, De Fabiani E, Macchioni D, Carulli L et al (2007) Age-related changes in bile acid synthesis and hepatic nuclear receptor expression. Eur J Clin Invest 37(6):501–508PubMedCrossRefGoogle Scholar
  24. Bishop NA, Guarente L (2007) Genetic links between diet and lifespan: shared mechanisms from yeast to humans. Nat Rev Genet 8(11):835–844PubMedCrossRefGoogle Scholar
  25. Black AE, Coward WA, Cole TJ, Prentice AM (1996) Human energy expenditure in affluent societies: an analysis of 574 doubly-labelled water measurements. Eur J Clin Nutr 50(2):72–92PubMedGoogle Scholar
  26. Boden G, Chen X, Polansky M (1999) Disruption of circadian insulin secretion is associated with reduced glucose uptake in first-degree relatives of patients with type 2 diabetes. Diabetes 48(11):2182–2188PubMedCrossRefGoogle Scholar
  27. Boivin DB, Czeisler CA (1998) Resetting of circadian melatonin and cortisol rhythms in humans by ordinary room light. NeuroReport 9(5):779–782PubMedCrossRefGoogle Scholar
  28. Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Invest 123(3):951–957PubMedPubMedCentralCrossRefGoogle Scholar
  29. Brown SA, Pagani L, Cajochen C, Eckert A (2011) Systemic and cellular reflections on ageing and the circadian oscillator: a mini-review. Gerontology 57(5):427–434PubMedGoogle Scholar
  30. Bryant CD, Parker CC, Zhou L, Olker C, Chandrasekaran RY, Wager TT, Bolivar VJ, Loudon AS, Vitaterna MH, Turek FW et al (2012) Csnk1e is a genetic regulator of sensitivity to psychostimulants and opioids. Neuropsychopharmacology 37(4):1026–1035PubMedCrossRefGoogle Scholar
  31. Bunger MK, Wilsbacher LD, Moran SM, Clendenin C, Radcliffe LA, Hogenesch JB, Simon MC, Takahashi JS, Bradfield CA (2000) Mop3 is an essential component of the master circadian pacemaker in mammals. Cell 103(7):1009–1017PubMedPubMedCentralCrossRefGoogle Scholar
  32. Canaple L, Rambaud J, Dkhissi-Benyahya O, Rayet B, Tan NS, Michalik L, Delaunay F, Wahli W, Laudet V (2006) Reciprocal regulation of brain and muscle Arnt-like protein 1 and peroxisome proliferator-activated receptor alpha defines a novel positive feedback loop in the rodent liver circadian clock. Mol Endocrinol 20(8):1715–1727PubMedCrossRefGoogle Scholar
  33. Cefalu WT, Wang ZQ, Werbel S, Bell-Farrow A, Crouse JR 3rd, Hinson WH, Terry JG, Anderson R (1995) Contribution of visceral fat mass to the insulin resistance of aging. Metabolism 44(7):954–959PubMedCrossRefGoogle Scholar
  34. Chaix A, Zarrinpar A, Miu P, Panda S (2014) Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab 20(6):991–1005PubMedPubMedCentralCrossRefGoogle Scholar
  35. Chang HC, Guarente L (2013) SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell 153(7):1448–1460PubMedPubMedCentralCrossRefGoogle Scholar
  36. Chang HC, Guarente L (2014) SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab 25(3):138–145PubMedCrossRefGoogle Scholar
  37. Chang MR, Goswami D, Mercer BA, Griffin PR (2012) The therapeutic potential of RORgamma modulators in the treatment of human disease. J Exp Pharmacol 4:141–148PubMedPubMedCentralGoogle Scholar
  38. Chang MR, He Y, Khan TM, Kuruvilla DS, Garcia-Ordonez R, Corzo CA, Unger TJ, White DW, Khan S, Lin L et al (2015) Antiobesity effect of a small molecule repressor of RORgamma. Mol Pharmacol 88(1):48–56PubMedPubMedCentralCrossRefGoogle Scholar
  39. Chen Z, McKnight SL (2007) A conserved DNA damage response pathway responsible for coupling the cell division cycle to the circadian and metabolic cycles. Cell Cycle 6(23):2906–2912PubMedCrossRefGoogle Scholar
  40. Chen Z, Odstrcil EA, Tu BP, McKnight SL (2007) Restriction of DNA replication to the reductive phase of the metabolic cycle protects genome integrity. Science 316(5833):1916–1919PubMedCrossRefGoogle Scholar
  41. Chen Z, Yoo SH, Park YS, Kim KH, Wei S, Buhr E, Ye ZY, Pan HL, Takahashi JS (2012) Identification of diverse modulators of central and peripheral circadian clocks by high-throughput chemical screening. Proc Natl Acad Sci U S A 109(1):101–106PubMedCrossRefGoogle Scholar
  42. Chen Z, Yoo SH, Takahashi JS (2013) Small molecule modifiers of circadian clocks. Cell Mol Life Sci 70(16):2985–2998PubMedCrossRefGoogle Scholar
  43. Crane JD, Devries MC, Safdar A, Hamadeh MJ, Tarnopolsky MA (2010) The effect of aging on human skeletal muscle mitochondrial and intramyocellular lipid ultrastructure. J Gerontol A Biol Sci Med Sci 65(2):119–128PubMedCrossRefGoogle Scholar
  44. Czeisler CA, Kronauer RE, Allan JS, Duffy JF, Jewett ME, Brown EN, Ronda JM (1989) Bright light induction of strong (type 0) resetting of the human circadian pacemaker. Science 244(4910):1328–1333PubMedCrossRefGoogle Scholar
  45. Czeisler CA, Dumont M, Duffy JF, Steinberg JD, Richardson GS, Brown EN, Sanchez R, Rios CD, Ronda JM (1992) Association of sleep-wake habits in older people with changes in output of circadian pacemaker. Lancet 340(8825):933–936PubMedCrossRefGoogle Scholar
  46. Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, Rimmer DW, Ronda JM, Silva EJ, Allan JS, Emens JS et al (1999) Stability, precision, and near-24-hour period of the human circadian pacemaker. Science 284(5423):2177–2181PubMedCrossRefGoogle Scholar
  47. Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U (2000) Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev 14(23):2950–2961PubMedPubMedCentralCrossRefGoogle Scholar
  48. Davidson MB (1979) The effect of aging on carbohydrate metabolism: a review of the English literature and a practical approach to the diagnosis of diabetes mellitus in the elderly. Metabolism 28(6):688–705PubMedCrossRefGoogle Scholar
  49. Defronzo RA (1979) Glucose intolerance and aging: evidence for tissue insensitivity to insulin. Diabetes 28(12):1095–1101PubMedCrossRefGoogle Scholar
  50. Dietz WH, Baur LA, Hall K, Puhl RM, Taveras EM, Uauy R, Kopelman P (2015) Management of obesity: improvement of health-care training and systems for prevention and care. Lancet 385(9986):2521–2533PubMedCrossRefGoogle Scholar
  51. Dominguez LJ, Barbagallo M (2016) The biology of the metabolic syndrome and aging. Curr Opin Clin Nutr Metab Care 19(1):5–11PubMedCrossRefGoogle Scholar
  52. Duffy JF, Zeitzer JM, Rimmer DW, Klerman EB, Dijk DJ, Czeisler CA (2002) Peak of circadian melatonin rhythm occurs later within the sleep of older subjects. Am J Physiol Endocrinol Metab 282(2):E297–E303PubMedCrossRefGoogle Scholar
  53. Dyar KA, Ciciliot S, Wright LE, Bienso RS, Tagliazucchi GM, Patel VR, Forcato M, Paz MI, Gudiksen A, Solagna F et al (2014) Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock. Mol Metab 3(1):29–41PubMedCrossRefGoogle Scholar
  54. Eckel-Mahan KL, Patel VR, de Mateo S, Orozco-Solis R, Ceglia NJ, Sahar S, Dilag-Penilla SA, Dyar KA, Baldi P, Sassone-Corsi P (2013) Reprogramming of the circadian clock by nutritional challenge. Cell 155(7):1464–1478PubMedPubMedCentralCrossRefGoogle Scholar
  55. Einarsson K, Nilsell K, Leijd B, Angelin B (1985) Influence of age on secretion of cholesterol and synthesis of bile acids by the liver. N Engl J Med 313(5):277–282PubMedCrossRefGoogle Scholar
  56. Escobar C, Cailotto C, Angeles-Castellanos M, Delgado RS, Buijs RM (2009) Peripheral oscillators: the driving force for food-anticipatory activity. Eur J Neurosci 30(9):1665–1675PubMedCrossRefGoogle Scholar
  57. Evans M, Sharma P, Guthrie N (2012) Bioavailability of citrus polymethoxylated flavones and their biological role in metabolic syndrome and hyperlipidemia. In: InTech, pp 1–19Google Scholar
  58. Finkel T (2015) The metabolic regulation of aging. Nat Med 21(12):1416–1423PubMedCrossRefGoogle Scholar
  59. Fonken LK, Nelson RJ (2014) The effects of light at night on circadian clocks and metabolism. Endocr Rev 35(4):648–670PubMedCrossRefGoogle Scholar
  60. Frank SA, Roland DC, Sturis J, Byrne MM, Refetoff S, Polonsky KS, Van Cauter E (1995) Effects of aging on glucose regulation during wakefulness and sleep. Am J Physiol 269(6 Pt 1):E1006–E1016PubMedGoogle Scholar
  61. Gallego M, Virshup DM (2007) Post-translational modifications regulate the ticking of the circadian clock. Nat Rev Mol Cell Biol 8(2):139–148PubMedCrossRefGoogle Scholar
  62. Garten A, Schuster S, Penke M, Gorski T, de Giorgis T, Kiess W (2015) Physiological and pathophysiological roles of NAMPT and NAD metabolism. Nat Rev Endocrinol 11(9):535–546PubMedGoogle Scholar
  63. Gerhart-Hines Z, Lazar MA (2015) Circadian metabolism in the light of evolution. Endocr Rev 36(3):289–304PubMedPubMedCentralCrossRefGoogle Scholar
  64. Gibson EM, Williams WP 3rd, Kriegsfeld LJ (2009) Aging in the circadian system: considerations for health, disease prevention and longevity. Exp Gerontol 44(1–2):51–56PubMedCrossRefGoogle Scholar
  65. Gill S, Le HD, Melkani GC, Panda S (2015) Time-restricted feeding attenuates age-related cardiac decline in Drosophila. Science 347(6227):1265–1269PubMedPubMedCentralCrossRefGoogle Scholar
  66. Giorgio M, Trinei M, Migliaccio E, Pelicci PG (2007) Hydrogen peroxide: a metabolic by-product or a common mediator of ageing signals? Nat Rev Mol Cell Biol 8(9):722–728PubMedCrossRefGoogle Scholar
  67. Gonzalez-Covarrubias V, Beekman M, Uh HW, Dane A, Troost J, Paliukhovich I, van der Kloet FM, Houwing-Duistermaat J, Vreeken RJ, Hankemeier T et al (2013) Lipidomics of familial longevity. Aging Cell 12(3):426–434PubMedPubMedCentralCrossRefGoogle Scholar
  68. Gorbacheva VY, Kondratov RV, Zhang R, Cherukuri S, Gudkov AV, Takahashi JS, Antoch MP (2005) Circadian sensitivity to the chemotherapeutic agent cyclophosphamide depends on the functional status of the CLOCK/BMAL1 transactivation complex. Proc Natl Acad Sci U S A 102(9):3407–3412PubMedPubMedCentralCrossRefGoogle Scholar
  69. Gorrini C, Harris IS, Mak TW (2013) Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 12(12):931–947PubMedCrossRefGoogle Scholar
  70. Green CB, Takahashi JS, Bass J (2008) The meter of metabolism. Cell 134(5):728–742PubMedPubMedCentralCrossRefGoogle Scholar
  71. Gutman R, Genzer Y, Chapnik N, Miskin R, Froy O (2011) Long-lived mice exhibit 24 h locomotor circadian rhythms at young and old age. Exp Gerontol 46(7):606–609PubMedCrossRefGoogle Scholar
  72. Harfmann BD, Schroder EA, Kachman MT, Hodge BA, Zhang X, Esser KA (2016) Muscle-specific loss of Bmal1 leads to disrupted tissue glucose metabolism and systemic glucose homeostasis. Skelet Muscle 6:12PubMedPubMedCentralCrossRefGoogle Scholar
  73. Hatori M, Vollmers C, Zarrinpar A, DiTacchio L, Bushong EA, Gill S, Leblanc M, Chaix A, Joens M, Fitzpatrick JA et al (2012) Time-restricted feeding without reducing caloric intake prevents metabolic diseases in mice fed a high-fat diet. Cell Metab 15(6):848–860PubMedPubMedCentralCrossRefGoogle Scholar
  74. He B, Chen Z (2016) Molecular targets for small-molecule modulators of circadian clocks. Curr Drug Metab 17(5):503–512PubMedPubMedCentralCrossRefGoogle Scholar
  75. He B, Nohara K, Park N, Park YS, Guillory B, Zhao Z, Garcia JM, Koike N, Lee CC, Takahashi JS et al (2016) The small molecule nobiletin targets the molecular oscillator to enhance circadian rhythms and protect against metabolic syndrome. Cell Metab 23(4):610–621PubMedPubMedCentralCrossRefGoogle Scholar
  76. Helleboid S, Haug C, Lamottke K, Zhou Y, Wei J, Daix S, Cambula L, Rigou G, Hum DW, Walczak R (2014) The identification of naturally occurring neoruscogenin as a bioavailable, potent, and high-affinity agonist of the nuclear receptor RORalpha (NR1F1). J Biomol Screen 19(3):399–406PubMedCrossRefGoogle Scholar
  77. Hirota T, Kay SA (2009) High-throughput screening and chemical biology: new approaches for understanding circadian clock mechanisms. Chem Biol 16(9):921–927PubMedPubMedCentralCrossRefGoogle Scholar
  78. Hirota T, Lee JW, Lewis WG, Zhang EE, Breton G, Liu X, Garcia M, Peters EC, Etchegaray JP, Traver D et al (2010) High-throughput chemical screen identifies a novel potent modulator of cellular circadian rhythms and reveals CKIalpha as a clock regulatory kinase. PLoS Biol 8(12):e1000559PubMedPubMedCentralCrossRefGoogle Scholar
  79. Hirota T, Lee JW, John PCS, Sawa M, Iwaisako K, Noguchi T, Pongsawakul PY, Sonntag T, Welsh DK, Brenner DA et al (2012) Identification of small molecule activators of cryptochrome. Science 337(6098):1094–1097Google Scholar
  80. Hofman MA, Swaab DF (2006) Living by the clock: the circadian pacemaker in older people. Ageing Res Rev 5(1):33–51PubMedCrossRefGoogle Scholar
  81. Hofstra WA, de Weerd AW (2008) How to assess circadian rhythm in humans: a review of literature. Epilepsy Behav 13(3):438–444PubMedCrossRefGoogle Scholar
  82. Hogenesch JB, Ueda HR (2011) Understanding systems-level properties: timely stories from the study of clocks. Nat Rev Genet 12(6):407–416PubMedCrossRefGoogle Scholar
  83. Hubbard BP, Sinclair DA (2014) Small molecule SIRT1 activators for the treatment of aging and age-related diseases. Trends Pharmacol Sci 35(3):146–154PubMedPubMedCentralCrossRefGoogle Scholar
  84. Huh JR, Leung MW, Huang P, Ryan DA, Krout MR, Malapaka RR, Chow J, Manel N, Ciofani M, Kim SV et al (2011) Digoxin and its derivatives suppress TH17 cell differentiation by antagonizing RORgamma activity. Nature 472(7344):486–490PubMedPubMedCentralCrossRefGoogle Scholar
  85. Humphries PS, Bersot R, Kincaid J, Mabery E, McCluskie K, Park T, Renner T, Riegler E, Steinfeld T, Turtle ED et al (2016) Carbazole-containing sulfonamides and sulfamides: discovery of cryptochrome modulators as antidiabetic agents. Bioorg Med Chem Lett 26(3):757–760PubMedCrossRefGoogle Scholar
  86. Imai S, Guarente L (2014) NAD+ and sirtuins in aging and disease. Trends Cell Biol 24(8):464–471PubMedPubMedCentralCrossRefGoogle Scholar
  87. Ingle KA, Kain V, Goel M, Prabhu SD, Young ME, Halade GV (2015) Cardiomyocyte-specific Bmal1 deletion in mice triggers diastolic dysfunction, extracellular matrix response, and impaired resolution of inflammation. Am J Physiol Heart Circ Physiol 309(11):H1827–H1836PubMedPubMedCentralCrossRefGoogle Scholar
  88. Isojima Y, Nakajima M, Ukai H, Fujishima H, Yamada RG, Masumoto KH, Kiuchi R, Ishida M, Ukai-Tadenuma M, Minami Y et al (2009) CKIepsilon/delta-dependent phosphorylation is a temperature-insensitive, period-determining process in the mammalian circadian clock. Proc Natl Acad Sci U S A 106(37):15744–15749PubMedPubMedCentralCrossRefGoogle Scholar
  89. Jacobi D, Liu S, Burkewitz K, Kory N, Knudsen NH, Alexander RK, Unluturk U, Li X, Kong X, Hyde AL et al (2015) Hepatic Bmal1 regulates rhythmic mitochondrial dynamics and promotes metabolic fitness. Cell Metab 22(4):709–720PubMedPubMedCentralCrossRefGoogle Scholar
  90. Jeong K, He B, Nohara K, Park N, Shin Y, Kim S, Shimomura K, Koike N, Yoo SH, Chen Z (2015) Dual attenuation of proteasomal and autophagic BMAL1 degradation in Clock Delta19/+ mice contributes to improved glucose homeostasis. Sci Rep 5:12801PubMedPubMedCentralCrossRefGoogle Scholar
  91. Jetten AM, Kang HS, Takeda Y (2013) Retinoic acid-related orphan receptors alpha and gamma: key regulators of lipid/glucose metabolism, inflammation, and insulin sensitivity. Front Endocrinol (Lausanne) 4:1Google Scholar
  92. Jin L, Martynowski D, Zheng S, Wada T, Xie W, Li Y (2010) Structural basis for hydroxycholesterols as natural ligands of orphan nuclear receptor RORgamma. Mol Endocrinol 24(5):923–929PubMedPubMedCentralCrossRefGoogle Scholar
  93. Jones KA, Hatori M, Mure LS, Bramley JR, Artymyshyn R, Hong SP, Marzabadi M, Zhong H, Sprouse J, Zhu Q et al (2013) Small-molecule antagonists of melanopsin-mediated phototransduction. Nat Chem Biol 9(10):630–635PubMedPubMedCentralCrossRefGoogle Scholar
  94. Jordan SD, Lamia KA (2013) AMPK at the crossroads of circadian clocks and metabolism. Mol Cell Endocrinol 366(2):163–169PubMedCrossRefGoogle Scholar
  95. Ju YE, Lucey BP, Holtzman DM (2014) Sleep and Alzheimer disease pathology–a bidirectional relationship. Nat Rev Neurol 10(2):115–119PubMedCrossRefGoogle Scholar
  96. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K (2006) Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116(7):1784–1792PubMedPubMedCentralCrossRefGoogle Scholar
  97. Kaeberlein M, McVey M, Guarente L (1999) The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms. Genes Dev 13(19):2570–2580PubMedPubMedCentralCrossRefGoogle Scholar
  98. Kahn BB (1996) Lilly lecture 1995. Glucose transport: pivotal step in insulin action. Diabetes 45(11):1644–1654PubMedCrossRefGoogle Scholar
  99. Kallen JA, Schlaeppi JM, Bitsch F, Geisse S, Geiser M, Delhon I, Fournier B (2002) X-ray structure of the hRORalpha LBD at 1.63 A: structural and functional data that cholesterol or a cholesterol derivative is the natural ligand of RORalpha. Structure 10(12):1697–1707PubMedCrossRefGoogle Scholar
  100. Katewa SD, Akagi K, Bose N, Rakshit K, Camarella T, Zheng X, Hall D, Davis S, Nelson CS, Brem RB et al (2016) Peripheral circadian clocks mediate dietary restriction-dependent changes in lifespan and fat metabolism in drosophila. Cell Metab 23(1):143–154PubMedCrossRefGoogle Scholar
  101. Kenney WL, Munce TA (2003) Invited review: aging and human temperature regulation. J Appl Physiol (1985) 95(6):2598–2603Google Scholar
  102. Khapre RV, Patel SA, Kondratova AA, Chaudhary A, Velingkaar N, Antoch MP, Kondratov RV (2014) Metabolic clock generates nutrient anticipation rhythms in mTOR signaling. Aging (Albany NY) 6(8):675–689CrossRefGoogle Scholar
  103. Kohsaka A, Laposky AD, Ramsey KM, Estrada C, Joshu C, Kobayashi Y, Turek FW, Bass J (2007) High-fat diet disrupts behavioral and molecular circadian rhythms in mice. Cell Metab 6(5):414–421PubMedCrossRefGoogle Scholar
  104. Kohsaka A, Das P, Hashimoto I, Nakao T, Deguchi Y, Gouraud SS, Waki H, Muragaki Y, Maeda M (2014) The circadian clock maintains cardiac function by regulating mitochondrial metabolism in mice. PLoS ONE 9(11):e112811PubMedPubMedCentralCrossRefGoogle Scholar
  105. Koike N, Yoo SH, Huang HC, Kumar V, Lee C, Kim TK, Takahashi JS (2012) Transcriptional architecture and chromatin landscape of the core circadian clock in mammals. Science 338(6105):349–354PubMedPubMedCentralCrossRefGoogle Scholar
  106. Kojetin DJ, Burris TP (2014) REV-ERB and ROR nuclear receptors as drug targets. Nat Rev Drug Discov 13(3):197–216PubMedPubMedCentralCrossRefGoogle Scholar
  107. Kolker DE, Fukuyama H, Huang DS, Takahashi JS, Horton TH, Turek FW (2003) Aging alters circadian and light-induced expression of clock genes in golden hamsters. J Biol Rhythms 18(2):159–169PubMedCrossRefGoogle Scholar
  108. Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP (2006) Early aging and age-related pathologies in mice deficient in BMAL1, the core component of the circadian clock. Genes Dev 20(14):1868–1873PubMedPubMedCentralCrossRefGoogle Scholar
  109. Kondratov RV, Vykhovanets O, Kondratova AA, Antoch MP (2009) Antioxidant N-acetyl-l-cysteine ameliorates symptoms of premature aging associated with the deficiency of the circadian protein BMAL1. Aging (Albany NY) 1(12):979–987CrossRefGoogle Scholar
  110. Labrie F, Belanger A, Cusan L, Gomez JL, Candas B (1997) Marked decline in serum concentrations of adrenal C19 sex steroid precursors and conjugated androgen metabolites during aging. J Clin Endocrinol Metab 82(8):2396–2402PubMedCrossRefGoogle Scholar
  111. Lamia KA, Storch KF, Weitz CJ (2008) Physiological significance of a peripheral tissue circadian clock. Proc Natl Acad Sci U S A 105(39):15172–15177PubMedPubMedCentralCrossRefGoogle Scholar
  112. Lamia KA, Sachdeva UM, DiTacchio L, Williams EC, Alvarez JG, Egan DF, Vasquez DS, Juguilon H, Panda S, Shaw RJ et al (2009) AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation. Science 326(5951):437–440PubMedPubMedCentralCrossRefGoogle Scholar
  113. Larsson NG (2010) Somatic mitochondrial DNA mutations in mammalian aging. Annu Rev Biochem 79:683–706PubMedCrossRefGoogle Scholar
  114. Lee Y, Chen R, Lee HM, Lee C (2011) Stoichiometric relationship among clock proteins determines robustness of circadian rhythms. J Biol Chem 286(9):7033–7042PubMedPubMedCentralCrossRefGoogle Scholar
  115. Lee YS, Cha BY, Choi SS, Choi BK, Yonezawa T, Teruya T, Nagai K, Woo JT (2013) Nobiletin improves obesity and insulin resistance in high-fat diet-induced obese mice. J Nutr Biochem 24(1):156–162PubMedCrossRefGoogle Scholar
  116. Levi F, Schibler U (2007) Circadian rhythms: mechanisms and therapeutic implications. Annu Rev Pharmacol Toxicol 47:593–628PubMedCrossRefGoogle Scholar
  117. Ling C, Poulsen P, Carlsson E, Ridderstrale M, Almgren P, Wojtaszewski J, Beck-Nielsen H, Groop L, Vaag A (2004) Multiple environmental and genetic factors influence skeletal muscle PGC-1alpha and PGC-1beta gene expression in twins. J Clin Invest 114(10):1518–1526PubMedPubMedCentralCrossRefGoogle Scholar
  118. Liu AC, Lewis WG, Kay SA (2007a) Mammalian circadian signaling networks and therapeutic targets. Nat Chem Biol 3(10):630–639PubMedCrossRefGoogle Scholar
  119. Liu AC, Welsh DK, Ko CH, Tran HG, Zhang EE, Priest AA, Buhr ED, Singer O, Meeker K, Verma IM et al (2007b) Intercellular coupling confers robustness against mutations in the SCN circadian clock network. Cell 129(3):605–616PubMedPubMedCentralCrossRefGoogle Scholar
  120. Longo VD, Panda S (2016) Fasting, circadian rhythms, and time-restricted feeding in healthy lifespan. Cell Metab 23(6):1048–1059PubMedPubMedCentralCrossRefGoogle Scholar
  121. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153(6):1194–1217PubMedPubMedCentralCrossRefGoogle Scholar
  122. Lopez-Otin C, Galluzzi L, Freije JM, Madeo F, Kroemer G (2016) Metabolic control of longevity. Cell 166(4):802–821PubMedCrossRefGoogle Scholar
  123. Lowell BB, Shulman GI (2005) Mitochondrial dysfunction and type 2 diabetes. Science 307(5708):384–387PubMedCrossRefGoogle Scholar
  124. Ma Q (2013) Role of nrf2 in oxidative stress and toxicity. Annu Rev Pharmacol Toxicol 53:401–426PubMedPubMedCentralCrossRefGoogle Scholar
  125. Ma S, Yim SH, Lee SG, Kim EB, Lee SR, Chang KT, Buffenstein R, Lewis KN, Park TJ, Miller RA et al (2015) Organization of the mammalian metabolome according to organ function, lineage specialization, and longevity. Cell Metab 22(2):332–343PubMedPubMedCentralCrossRefGoogle Scholar
  126. Marcheva B, Ramsey KM, Buhr ED, Kobayashi Y, Su H, Ko CH, Ivanova G, Omura C, Mo S, Vitaterna MH et al (2010) Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 466(7306):627–631PubMedPubMedCentralCrossRefGoogle Scholar
  127. Martinez-Lozano Sinues P, Tarokh L, Li X, Kohler M, Brown SA, Zenobi R, Dallmann R (2014) Circadian variation of the human metabolome captured by real-time breath analysis. PLoS ONE 9(12):e114422PubMedPubMedCentralCrossRefGoogle Scholar
  128. Masri S, Rigor P, Cervantes M, Ceglia N, Sebastian C, Xiao C, Roqueta-Rivera M, Deng C, Osborne TF, Mostoslavsky R et al (2014) Partitioning circadian transcription by SIRT6 leads to segregated control of cellular metabolism. Cell 158(3):659–672PubMedPubMedCentralCrossRefGoogle Scholar
  129. Matsuzaki K, Miyazaki K, Sakai S, Yawo H, Nakata N, Moriguchi S, Fukunaga K, Yokosuka A, Sashida Y, Mimaki Y et al (2008) Nobiletin, a citrus flavonoid with neurotrophic action, augments protein kinase A-mediated phosphorylation of the AMPA receptor subunit, GluR1, and the postsynaptic receptor response to glutamate in murine hippocampus. Eur J Pharmacol 578(2–3):194–200PubMedCrossRefGoogle Scholar
  130. McArthur AJ, Gillette MU, Prosser RA (1991) Melatonin directly resets the rat suprachiasmatic circadian clock in vitro. Brain Res 565(1):158–161PubMedCrossRefGoogle Scholar
  131. Merksamer PI, Liu Y, He W, Hirschey MD, Chen D, Verdin E (2013) The sirtuins, oxidative stress and aging: an emerging link. Aging (Albany NY) 5(3):144–150CrossRefGoogle Scholar
  132. Miller BH, McDearmon EL, Panda S, Hayes KR, Zhang J, Andrews JL, Antoch MP, Walker JR, Esser KA, Hogenesch JB et al (2007) Circadian and CLOCK-controlled regulation of the mouse transcriptome and cell proliferation. Proc Natl Acad Sci U S A 104(9):3342–3347PubMedPubMedCentralCrossRefGoogle Scholar
  133. Minami Y, Kasukawa T, Kakazu Y, Iigo M, Sugimoto M, Ikeda S, Yasui A, van der Horst GT, Soga T, Ueda HR (2009) Measurement of internal body time by blood metabolomics. Proc Natl Acad Sci U S A 106(24):9890–9895PubMedPubMedCentralCrossRefGoogle Scholar
  134. Mistlberger RE (2011) Neurobiology of food anticipatory circadian rhythms. Physiol Behav 104(4):535–545PubMedCrossRefGoogle Scholar
  135. Monk TH, Buysse DJ, Reynolds CF 3rd, Kupfer DJ, Houck PR (1995) Circadian temperature rhythms of older people. Exp Gerontol 30(5):455–474PubMedCrossRefGoogle Scholar
  136. Morgan AE, Mooney KM, Wilkinson SJ, Pickles NA, Mc Auley MT (2016) Cholesterol metabolism: a review of how ageing disrupts the biological mechanisms responsible for its regulation. Ageing Res Rev 27:108–124PubMedCrossRefGoogle Scholar
  137. Mulvihill EE, Assini JM, Lee JK, Allister EM, Sutherland BG, Koppes JB, Sawyez CG, Edwards JY, Telford DE, Charbonneau A et al (2011) Nobiletin attenuates VLDL overproduction, dyslipidemia, and atherosclerosis in mice with diet-induced insulin resistance. Diabetes 60(5):1446–1457PubMedPubMedCentralCrossRefGoogle Scholar
  138. Munch M, Knoblauch V, Blatter K, Schroder C, Schnitzler C, Krauchi K, Wirz-Justice A, Cajochen C (2005) Age-related attenuation of the evening circadian arousal signal in humans. Neurobiol Aging 26(9):1307–1319PubMedCrossRefGoogle Scholar
  139. Nair KS (2005) Aging muscle. Am J Clin Nutr 81(5):953–963PubMedGoogle Scholar
  140. Nakahata Y, Kaluzova M, Grimaldi B, Sahar S, Hirayama J, Chen D, Guarente LP, Sassone-Corsi P (2008) The NAD+ -dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 134(2):329–340PubMedPubMedCentralCrossRefGoogle Scholar
  141. Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P (2009) Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science 324(5927):654–657PubMedCrossRefGoogle Scholar
  142. Nakamura TJ, Nakamura W, Yamazaki S, Kudo T, Cutler T, Colwell CS, Block GD (2011) Age-related decline in circadian output. J Neurosci 31(28):10201–10205PubMedPubMedCentralCrossRefGoogle Scholar
  143. Nakamura TJ, Nakamura W, Tokuda IT, Ishikawa T, Kudo T, Colwell CS, Block GD (2015) Age-related changes in the circadian system unmasked by constant conditions (1,2,3). eNeuro 2(4)Google Scholar
  144. Neufer PD, Bamman MM, Muoio DM, Bouchard C, Cooper DM, Goodpaster BH, Booth FW, Kohrt WM, Gerszten RE, Mattson MP et al (2015) Understanding the cellular and molecular mechanisms of physical activity-induced health benefits. Cell Metab 22(1):4–11PubMedCrossRefGoogle Scholar
  145. Nguyen D, Samson SL, Reddy VT, Gonzalez EV, Sekhar RV (2013) Impaired mitochondrial fatty acid oxidation and insulin resistance in aging: novel protective role of glutathione. Aging Cell 12(3):415–425PubMedCrossRefGoogle Scholar
  146. Nohara K, Yoo SH, Chen ZJ (2015a) Manipulating the circadian and sleep cycles to protect against metabolic disease. Front Endocrinol (Lausanne) 6:35Google Scholar
  147. Nohara K, Shin Y, Park N, Jeong K, He B, Koike N, Yoo SH, Chen Z (2015b) Ammonia-lowering activities and carbamoyl phosphate synthetase 1 (Cps1) induction mechanism of a natural flavonoid. Nutr Metab (Lond) 12:23CrossRefGoogle Scholar
  148. Noureddin M, Yates KP, Vaughn IA, Neuschwander-Tetri BA, Sanyal AJ, McCullough A, Merriman R, Hameed B, Doo E, Kleiner DE et al (2013) Clinical and histological determinants of nonalcoholic steatohepatitis and advanced fibrosis in elderly patients. Hepatology 58(5):1644–1654PubMedPubMedCentralCrossRefGoogle Scholar
  149. Okada-Iwabu M, Yamauchi T, Iwabu M, Honma T, Hamagami K, Matsuda K, Yamaguchi M, Tanabe H, Kimura-Someya T, Shirouzu M et al (2013) A small-molecule AdipoR agonist for type 2 diabetes and short life in obesity. Nature 503(7477):493–499PubMedCrossRefGoogle Scholar
  150. Okazaki H, Matsunaga N, Fujioka T, Okazaki F, Akagawa Y, Tsurudome Y, Ono M, Kuwano M, Koyanagi S, Ohdo S (2014) Circadian regulation of mTOR by the ubiquitin pathway in renal cell carcinoma. Cancer Res 74(2):543–551PubMedCrossRefGoogle Scholar
  151. Oosterman JE, Kalsbeek A, la Fleur SE, Belsham DD (2015) Impact of nutrients on circadian rhythmicity. Am J Physiol Regul Integr Comp Physiol 308(5):R337–R350PubMedCrossRefGoogle Scholar
  152. Pagani L, Schmitt K, Meier F, Izakovic J, Roemer K, Viola A, Cajochen C, Wirz-Justice A, Brown SA, Eckert A (2011) Serum factors in older individuals change cellular clock properties. Proc Natl Acad Sci U S A 108(17):7218–7223PubMedPubMedCentralCrossRefGoogle Scholar
  153. Panda S, Antoch MP, Miller BH, Su AI, Schook AB, Straume M, Schultz PG, Kay SA, Takahashi JS, Hogenesch JB (2002) Coordinated transcription of key pathways in the mouse by the circadian clock. Cell 109(3):307–320PubMedCrossRefGoogle Scholar
  154. Pannemans DL, Westerterp KR (1995) Energy expenditure, physical activity and basal metabolic rate of elderly subjects. Br J Nutr 73(4):571–581PubMedCrossRefGoogle Scholar
  155. Paschos GK, Ibrahim S, Song WL, Kunieda T, Grant G, Reyes TM, Bradfield CA, Vaughan CH, Eiden M, Masoodi M et al (2012) Obesity in mice with adipocyte-specific deletion of clock component Arntl. Nat Med 18(12):1768–1777PubMedPubMedCentralCrossRefGoogle Scholar
  156. Peek CB, Affinati AH, Ramsey KM, Kuo HY, Yu W, Sena LA, Ilkayeva O, Marcheva B, Kobayashi Y, Omura C et al (2013) Circadian clock NAD+ cycle drives mitochondrial oxidative metabolism in mice. Science 342(6158):1243417PubMedPubMedCentralCrossRefGoogle Scholar
  157. Pendergast JS, Branecky KL, Yang W, Ellacott KL, Niswender KD, Yamazaki S (2013) High-fat diet acutely affects circadian organisation and eating behavior. Eur J Neurosci 37(8):1350–1356PubMedPubMedCentralCrossRefGoogle Scholar
  158. Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300(5622):1140–1142PubMedPubMedCentralCrossRefGoogle Scholar
  159. Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI (2004) Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes. N Engl J Med 350(7):664–671PubMedPubMedCentralCrossRefGoogle Scholar
  160. Pierpaoli W, Regelson W (1994) Pineal control of aging: effect of melatonin and pineal grafting on aging mice. Proc Natl Acad Sci U S A 91(2):787–791PubMedPubMedCentralCrossRefGoogle Scholar
  161. Ramkisoensing A, Meijer JH (2015) Synchronization of biological clock neurons by light and peripheral feedback systems promotes circadian rhythms and health. Front Neurol 6:128PubMedPubMedCentralCrossRefGoogle Scholar
  162. Ramsey KM, Mills KF, Satoh A, Imai S (2008) Age-associated loss of Sirt1-mediated enhancement of glucose-stimulated insulin secretion in beta cell-specific Sirt1-overexpressing (BESTO) mice. Aging Cell 7(1):78–88PubMedCrossRefGoogle Scholar
  163. Ramsey KM, Yoshino J, Brace CS, Abrassart D, Kobayashi Y, Marcheva B, Hong HK, Chong JL, Buhr ED, Lee C et al (2009) Circadian clock feedback cycle through NAMPT-mediated NAD+ biosynthesis. Science 324(5927):651–654PubMedPubMedCentralCrossRefGoogle Scholar
  164. Reddy AB, Karp NA, Maywood ES, Sage EA, Deery M, O’Neill JS, Wong GK, Chesham J, Odell M, Lilley KS et al (2006) Circadian orchestration of the hepatic proteome. Curr Biol 16(11):1107–1115PubMedCrossRefGoogle Scholar
  165. Regev A (2001) Schiff ER: liver disease in the elderly. Gastroenterol Clin North Am 30(2):547–563, x–xiGoogle Scholar
  166. Riemersma-van der Lek RF, Swaab DF, Twisk J, Hol EM, Hoogendijk WJ, Van Someren EJ (2008) Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. Jama 299(22):2642–2655Google Scholar
  167. Rivnay B, Bergman S, Shinitzky M, Globerson A (1980) Correlations between membrane viscosity, serum cholesterol, lymphocyte activation and aging in man. Mech Ageing Dev 12(2):119–126PubMedCrossRefGoogle Scholar
  168. Robles MS, Cox J, Mann M (2014) In-vivo quantitative proteomics reveals a key contribution of post-transcriptional mechanisms to the circadian regulation of liver metabolism. PLoS Genet 10(1):e1004047PubMedPubMedCentralCrossRefGoogle Scholar
  169. Roenneberg T, Allebrandt KV, Merrow M, Vetter C (2012) Social jetlag and obesity. Curr Biol 22(10):939–943PubMedCrossRefGoogle Scholar
  170. Rowe JW, Minaker KL, Pallotta JA, Flier JS (1983) Characterization of the insulin resistance of aging. J Clin Invest 71(6):1581–1587PubMedPubMedCentralCrossRefGoogle Scholar
  171. Ruderman NB, Carling D, Prentki M, Cacicedo JM (2013) AMPK, insulin resistance, and the metabolic syndrome. J Clin Invest 123(7):2764–2772PubMedPubMedCentralCrossRefGoogle Scholar
  172. Rutter J, Reick M, McKnight SL (2002) Metabolism and the control of circadian rhythms. Annu Rev Biochem 71:307–331PubMedCrossRefGoogle Scholar
  173. Sadacca LA, Lamia KA, deLemos AS, Blum B, Weitz CJ (2011) An intrinsic circadian clock of the pancreas is required for normal insulin release and glucose homeostasis in mice. Diabetologia 54(1):120–124PubMedCrossRefGoogle Scholar
  174. Sala ML, Roell B, van der Bijl N, van der Grond J, de Craen AJ, Slagboom EP, van der Geest R, de Roos A, Kroft LJ (2015) Genetically determined prospect to become long-lived is associated with less abdominal fat and in particular less abdominal visceral fat in men. Age Ageing 44(4):713–717PubMedCrossRefGoogle Scholar
  175. Salomon JA, Wang H, Freeman MK, Vos T, Flaxman AD, Lopez AD, Murray CJ (2012) Healthy life expectancy for 187 countries, 1990–2010: a systematic analysis for the Global Burden Disease Study 2010. Lancet 380(9859):2144–2162PubMedCrossRefGoogle Scholar
  176. Santori FR, Huang P, van de Pavert SA, Douglass EF Jr, Leaver DJ, Haubrich BA, Keber R, Lorbek G, Konijn T, Rosales BN et al (2015) Identification of natural RORgamma ligands that regulate the development of lymphoid cells. Cell Metab 21(2):286–297PubMedPubMedCentralCrossRefGoogle Scholar
  177. Sartori C, Dessen P, Mathieu C, Monney A, Bloch J, Nicod P, Scherrer U, Duplain H (2009) Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology 150(12):5311–5317PubMedCrossRefGoogle Scholar
  178. Sastre J, Pallardo FV, Pla R, Pellin A, Juan G, O’Connor JE, Estrela JM, Miquel J, Vina J (1996) Aging of the liver: age-associated mitochondrial damage in intact hepatocytes. Hepatology 24(5):1199–1205PubMedCrossRefGoogle Scholar
  179. Sastre J, Pallardo FV, Vina J (2003) The role of mitochondrial oxidative stress in aging. Free Radic Biol Med 35(1):1–8PubMedCrossRefGoogle Scholar
  180. Scheele C, Nielsen S, Pedersen BK (2009) ROS and myokines promote muscle adaptation to exercise. Trends Endocrinol Metab 20(3):95–99PubMedCrossRefGoogle Scholar
  181. Scheen AJ, Byrne MM, Plat L, Leproult R, Van Cauter E (1996) Relationships between sleep quality and glucose regulation in normal humans. Am J Physiol 271(2 Pt 1):E261–E270PubMedGoogle Scholar
  182. Scheer FA, Hilton MF, Mantzoros CS, Shea SA (2009) Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A 106(11):4453–4458PubMedPubMedCentralCrossRefGoogle Scholar
  183. Schmucker DL (2005) Age-related changes in liver structure and function: implications for disease? Exp Gerontol 40(8–9):650–659PubMedCrossRefGoogle Scholar
  184. Schriner SE, Linford NJ, Martin GM, Treuting P, Ogburn CE, Emond M, Coskun PE, Ladiges W, Wolf N, Van Remmen H et al (2005) Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 308(5730):1909–1911PubMedCrossRefGoogle Scholar
  185. Schroder EA, Esser KA (2013) Circadian rhythms, skeletal muscle molecular clocks, and exercise. Exerc Sport Sci Rev 41(4):224–229PubMedCrossRefGoogle Scholar
  186. Schroeder AM, Colwell CS (2013) How to fix a broken clock. Trends Pharmacol Sci 34(11):605–619PubMedCrossRefGoogle Scholar
  187. Schwartz WJ, Gainer H (1977) Suprachiasmatic nucleus: use of 14C-labeled deoxyglucose uptake as a functional marker. Science 197(4308):1089–1091PubMedCrossRefGoogle Scholar
  188. Sellix MT, Evans JA, Leise TL, Castanon-Cervantes O, Hill DD, DeLisser P, Block GD, Menaker M, Davidson AJ (2012) Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators. J Neurosci 32(46):16193–16202PubMedPubMedCentralCrossRefGoogle Scholar
  189. Seo AY, Joseph AM, Dutta D, Hwang JC, Aris JP, Leeuwenburgh C (2010) New insights into the role of mitochondria in aging: mitochondrial dynamics and more. J Cell Sci 123(Pt 15):2533–2542PubMedPubMedCentralCrossRefGoogle Scholar
  190. Sharma M, Palacios-Bois J, Schwartz G, Iskandar H, Thakur M, Quirion R, Nair NP (1989) Circadian rhythms of melatonin and cortisol in aging. Biol Psychiatry 25(3):305–319PubMedCrossRefGoogle Scholar
  191. Sheedfar F, Di Biase S, Koonen D, Vinciguerra M (2013) Liver diseases and aging: friends or foes? Aging Cell 12(6):950–954PubMedCrossRefGoogle Scholar
  192. Shi SQ, Ansari TS, McGuinness OP, Wasserman DH, Johnson CH (2013) Circadian disruption leads to insulin resistance and obesity. Curr Biol 23(5):372–381PubMedPubMedCentralCrossRefGoogle Scholar
  193. Shulman AI, Mangelsdorf DJ (2005) Retinoid x receptor heterodimers in the metabolic syndrome. N Engl J Med 353(6):604–615PubMedCrossRefGoogle Scholar
  194. Silverstone FA, Brandfonbrener M, Shock NW, Yiengst MJ (1957) Age differences in the intravenous glucose tolerance tests and the response to insulin. J Clin Invest 36(3):504–514PubMedPubMedCentralCrossRefGoogle Scholar
  195. Solt LA, Wang Y, Banerjee S, Hughes T, Kojetin DJ, Lundasen T, Shin Y, Liu J, Cameron MD, Noel R et al (2012) Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists. Nature 485(7396):62–68PubMedPubMedCentralCrossRefGoogle Scholar
  196. Stephan FK (2002) The “other” circadian system: food as a Zeitgeber. J Biol Rhythms 17(4):284–292PubMedCrossRefGoogle Scholar
  197. Stokkan KA, Yamazaki S, Tei H, Sakaki Y, Menaker M (2001) Entrainment of the circadian clock in the liver by feeding. Science 291(5503):490–493PubMedCrossRefGoogle Scholar
  198. Storch KF, Lipan O, Leykin I, Viswanathan N, Davis FC, Wong WH, Weitz CJ (2002) Extensive and divergent circadian gene expression in liver and heart. Nature 417(6884):78–83PubMedCrossRefGoogle Scholar
  199. Takahashi JS, Hong HK, Ko CH, McDearmon EL (2008) The genetics of mammalian circadian order and disorder: implications for physiology and disease. Nat Rev Genet 9(10):764–775PubMedPubMedCentralCrossRefGoogle Scholar
  200. Takeda Y, Kang HS, Freudenberg J, DeGraff LM, Jothi R, Jetten AM (2014) Retinoic acid-related orphan receptor gamma (RORgamma): a novel participant in the diurnal regulation of hepatic gluconeogenesis and insulin sensitivity. PLoS Genet 10(5):e1004331PubMedPubMedCentralCrossRefGoogle Scholar
  201. Tevy MF, Giebultowicz J, Pincus Z, Mazzoccoli G, Vinciguerra M (2013) Aging signaling pathways and circadian clock-dependent metabolic derangements. Trends Endocrinol Metab 24(5):229–237PubMedPubMedCentralCrossRefGoogle Scholar
  202. Turek FW, Joshu C, Kohsaka A, Lin E, Ivanova G, McDearmon E, Laposky A, Losee-Olson S, Easton A, Jensen DR et al (2005) Obesity and metabolic syndrome in circadian Clock mutant mice. Science 308(5724):1043–1045PubMedPubMedCentralCrossRefGoogle Scholar
  203. Valentinuzzi VS, Scarbrough K, Takahashi JS, Turek FW (1997) Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice. Am J Physiol 273(6 Pt 2):R1957–R1964PubMedGoogle Scholar
  204. Vermeij WP, Hoeijmakers JH, Pothof J (2016) Genome integrity in aging: human syndromes, mouse models, and therapeutic options. Annu Rev Pharmacol Toxicol 56:427–445PubMedCrossRefGoogle Scholar
  205. Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS (1994) Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264(5159):719–725PubMedPubMedCentralCrossRefGoogle Scholar
  206. Vitiello MV, Smallwood RG, Avery DH, Pascualy RA, Martin DC, Prinz PN (1986) Circadian temperature rhythms in young adult and aged men. Neurobiol Aging 7(2):97–100PubMedCrossRefGoogle Scholar
  207. Waldhauser F, Weiszenbacher G, Tatzer E, Gisinger B, Waldhauser M, Schemper M, Frisch H (1988) Alterations in nocturnal serum melatonin levels in humans with growth and aging. J Clin Endocrinol Metab 66(3):648–652PubMedCrossRefGoogle Scholar
  208. Wallace DC (2005) A mitochondrial paradigm of metabolic and degenerative diseases, aging, and cancer: a dawn for evolutionary medicine. Annu Rev Genet 39:359–407PubMedPubMedCentralCrossRefGoogle Scholar
  209. Wallach T, Kramer A (2015) Chemical chronobiology: toward drugs manipulating time. FEBS Lett 589(14):1530–1538PubMedCrossRefGoogle Scholar
  210. Walle T (2007) Methoxylated flavones, a superior cancer chemopreventive flavonoid subclass? Semin Cancer Biol 17(5):354–362PubMedPubMedCentralCrossRefGoogle Scholar
  211. Walton KM, Fisher K, Rubitski D, Marconi M, Meng QJ, Sladek M, Adams J, Bass M, Chandrasekaran R, Butler T et al (2009) Selective inhibition of casein kinase 1 epsilon minimally alters circadian clock period. J Pharmacol Exp Ther 330(2):430–439PubMedCrossRefGoogle Scholar
  212. Wang N, Yang G, Jia Z, Zhang H, Aoyagi T, Soodvilai S, Symons JD, Schnermann JB, Gonzalez FJ, Litwin SE et al (2008) Vascular PPARgamma controls circadian variation in blood pressure and heart rate through Bmal1. Cell Metab 8(6):482–491PubMedPubMedCentralCrossRefGoogle Scholar
  213. Wang Y, Kumar N, Solt LA, Richardson TI, Helvering LM, Crumbley C, Garcia-Ordonez RD, Stayrook KR, Zhang X, Novick S et al (2010) Modulation of retinoic acid receptor-related orphan receptor alpha and gamma activity by 7-oxygenated sterol ligands. J Biol Chem 285(7):5013–5025PubMedCrossRefGoogle Scholar
  214. Weitzman ED, Moline ML, Czeisler CA, Zimmerman JC (1982) Chronobiology of aging: temperature, sleep-wake rhythms and entrainment. Neurobiol Aging 3(4):299–309PubMedCrossRefGoogle Scholar
  215. Welsh DK, Takahashi JS, Kay SA (2010) Suprachiasmatic nucleus: cell autonomy and network properties. Annu Rev Physiol 72:551–577PubMedPubMedCentralCrossRefGoogle Scholar
  216. Westermann B (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11(12):872–884PubMedCrossRefGoogle Scholar
  217. Wurtman RJ, Axelrod J, Phillips LS (1963) Melatonin synthesis in the pineal gland: control by light. Science 142(3595):1071–1073PubMedCrossRefGoogle Scholar
  218. Wyse CA, Coogan AN (2010) Impact of aging on diurnal expression patterns of CLOCK and BMAL1 in the mouse brain. Brain Res 1337:21–31PubMedCrossRefGoogle Scholar
  219. Xu T, Wang X, Zhong B, Nurieva RI, Ding S, Dong C (2011) Ursolic acid suppresses interleukin-17 (IL-17) production by selectively antagonizing the function of RORgamma t protein. J Biol Chem 286(26):22707–22710PubMedPubMedCentralCrossRefGoogle Scholar
  220. Yamauchi T, Nio Y, Maki T, Kobayashi M, Takazawa T, Iwabu M, Okada-Iwabu M, Kawamoto S, Kubota N, Kubota T et al (2007) Targeted disruption of AdipoR1 and AdipoR2 causes abrogation of adiponectin binding and metabolic actions. Nat Med 13(3):332–339PubMedCrossRefGoogle Scholar
  221. Yang X, Downes M, Yu RT, Bookout AL, He W, Straume M, Mangelsdorf DJ, Evans RM (2006) Nuclear receptor expression links the circadian clock to metabolism. Cell 126(4):801–810PubMedCrossRefGoogle Scholar
  222. Yang G, Chen L, Grant GR, Paschos G, Song WL, Musiek ES, Lee V, McLoughlin SC, Grosser T, Cotsarelis G et al (2016) Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival. Sci Transl Med 8(324):324ra316Google Scholar
  223. Yoo SH, Yamazaki S, Lowrey PL, Shimomura K, Ko CH, Buhr ED, Siepka SM, Hong HK, Oh WJ, Yoo OJ et al (2004) PERIOD2:LUCIFERASE real-time reporting of circadian dynamics reveals persistent circadian oscillations in mouse peripheral tissues. Proc Natl Acad Sci U S A 101(15):5339–5346PubMedPubMedCentralCrossRefGoogle Scholar
  224. Yoo SH, Mohawk JA, Siepka SM, Shan Y, Huh SK, Hong HK, Kornblum I, Kumar V, Koike N, Xu M et al (2013) Competing E3 ubiquitin ligases govern circadian periodicity by degradation of CRY in nucleus and cytoplasm. Cell 152(5):1091–1105PubMedPubMedCentralCrossRefGoogle Scholar
  225. Young ME, Brewer RA, Peliciari-Garcia RA, Collins HE, He L, Birky TL, Peden BW, Thompson EG, Ammons BJ, Bray MS et al (2014) Cardiomyocyte-specific BMAL1 plays critical roles in metabolism, signaling, and maintenance of contractile function of the heart. J Biol Rhythms 29(4):257–276PubMedPubMedCentralCrossRefGoogle Scholar
  226. Yu EA, Weaver DR (2011) Disrupting the circadian clock: gene-specific effects on aging, cancer, and other phenotypes. Aging (Albany NY) 3(5):479–493CrossRefGoogle Scholar
  227. Zhang R, Lahens NF, Ballance HI, Hughes ME, Hogenesch JB (2014a) A circadian gene expression atlas in mammals: implications for biology and medicine. Proc Natl Acad Sci USA 111(45):16219–16224PubMedPubMedCentralCrossRefGoogle Scholar
  228. Zhang D, Tong X, Arthurs B, Guha A, Rui L, Kamath A, Inoki K, Yin L (2014b) Liver clock protein BMAL1 promotes de novo lipogenesis through insulin-mTORC2-AKT signaling. J Biol Chem 289(37):25925–25935PubMedPubMedCentralCrossRefGoogle Scholar
  229. Zhang H, Ryu D, Wu Y, Gariani K, Wang X, Luan P, D’Amico D, Ropelle ER, Lutolf MP, Aebersold R et al (2016) NAD(+) repletion improves mitochondrial and stem cell function and enhances life span in mice. Science 352(6292):1436–1443PubMedCrossRefGoogle Scholar
  230. Zhao X, Hirota T, Han X, Cho H, Chong LW, Lamia K, Liu S, Atkins AR, Banayo E, Liddle C et al (2016) Circadian amplitude regulation via FBXW7-targeted REV-ERBalpha degradation. Cell 165(7):1644–1657PubMedPubMedCentralCrossRefGoogle Scholar
  231. Zheng X, Sehgal A (2010) AKT and TOR signaling set the pace of the circadian pacemaker. Curr Biol 20(13):1203–1208PubMedPubMedCentralCrossRefGoogle Scholar
  232. Zhu B, Gates LA, Stashi E, Dasgupta S, Gonzales N, Dean A, Dacso CC, York B, O’Malley BW (2015) Coactivator-dependent oscillation of chromatin accessibility dictates circadian gene amplitude via REV-ERB loading. Mol Cell 60(5):769–783PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Department of Biochemistry and Molecular BiologyThe University of Texas Health Science Center at HoustonHoustonUSA

Personalised recommendations