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The aging clock: circadian rhythms and later life


The aging clock: circadian rhythms and later life

Hood, Suzanne and Amir, Shimon ORCID: https://orcid.org/0000-0003-1919-5023 (2017) The aging clock: circadian rhythms and later life. Journal of Clinical Investigation, 127 (2). pp. 437-446. ISSN 0021-9738

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Official URL: http://dx.doi.org/10.1172/JCI90328


Circadian rhythms play an influential role in nearly all aspects of physiology and behavior in the vast majority of species on Earth. The biological clockwork that regulates these rhythms is dynamic over the lifespan: rhythmic activities such as sleep/wake patterns change markedly as we age, and in many cases they become increasingly fragmented. Given that prolonged disruptions of normal rhythms are highly detrimental to health, deeper knowledge of how our biological clocks change with age may create valuable opportunities to improve health and longevity for an aging global population. In this Review, we synthesize key findings from the study of circadian rhythms in later life, identify patterns of change documented to date, and review potential physiological mechanisms that may underlie these changes.

Divisions:Concordia University > Faculty of Arts and Science > Psychology
Item Type:Article
Authors:Hood, Suzanne and Amir, Shimon
Journal or Publication:Journal of Clinical Investigation
Date:February 2017
  • Natural Sciences and Engineering Research Council of Canada
  • Les Fonds de la recherche en santé Québec
  • Canadian Institutes for Health Research
Digital Object Identifier (DOI):10.1172/JCI90328
ID Code:983744
Deposited On:13 Apr 2018 15:33
Last Modified:13 Apr 2018 15:33


National Institute on Aging. Global Health and Aging. Report 11-7737. Bethesda, Maryland, USA: NIH, US Departments of Health and Human Services; 2011.

Kondratov RV. A role of the circadian system and circadian proteins in aging. Ageing Res Rev. 2007;6(1):12–27.

Kondratova AA, Kondratov RV. The circadian clock and pathology of the ageing brain. Nat Rev Neurosci. 2012;13(5):325–335.

Mattis J, Sehgal A. Circadian rhythms, sleep, and disorders of aging. Trends Endocrinol Metab. 2016;27(4):192–203.

Abbott SM, Videnovic A. Chronic sleep disturbance and neural injury: links to neurodegenerative disease. Nat Sci Sleep. 2016;8:55–61.

Stevens RG, Brainard GC, Blask DE, Lockley SW, Motta ME. Breast cancer and circadian disruption from electric lighting in the modern world. CA Cancer J Clin. 2014;64(3):207–218.

McFadden E, Jones ME, Schoemaker MJ, Ashworth A, Swerdlow AJ. The relationship between obesity and exposure to light at night: cross-sectional analyses of over 100,000 women in the Breakthrough Generations Study. Am J Epidemiol. 2014;180(3):245–250.

Lucassen EA, et al. Environmental 24-hr cycles are essential for health. Curr Biol. 2016;26(14):1843–1853.

Morris CJ, Purvis TE, Hu K, Scheer FA. Circadian misalignment increases cardiovascular disease risk factors in humans. Proc Natl Acad Sci U S A. 2016;113(10):E1402–E1411.

Arendt J. Biological rhythms during residence in polar regions. Chronobiol Int. 2012;29(4):379–394.

Welsh DK, Takahashi JS, Kay SA. Suprachiasmatic nucleus: cell autonomy and network properties. Annu Rev Physiol. 2010;72:551–577.

Dibner C, Schibler U. Circadian timing of metabolism in animal models and humans. J Intern Med. 2015;277(5):513–527.

Mohawk JA, Green CB, Takahashi JS. Central and peripheral circadian clocks in mammals. Annu Rev Neurosci. 2012;35:445–462.

Huang W, Ramsey KM, Marcheva B, Bass J. Circadian rhythms, sleep, and metabolism. J Clin Invest. 2011;121(6):2133–2141.

Duffield GE. DNA microarray analyses of circadian timing: the genomic basis of biological time. J Neuroendocrinol. 2003;15(10):991–1002.

Challet E. Minireview: Entrainment of the suprachiasmatic clockwork in diurnal and nocturnal mammals. Endocrinology. 2007;148(12):5648–5655.

Horne JA, Ostberg O. A self-assessment questionnaire to determine morningness-eveningness in human circadian rhythms. Int J Chronobiol. 1976;4(2):97–110.

Carrier J, Monk TH, Buysse DJ, Kupfer DJ. Sleep and morningness-eveningness in the ‘middle’ years of life (20–59 y). J Sleep Res. 1997;6(4):230–237.

Roenneberg T, et al. Epidemiology of the human circadian clock. Sleep Med Rev. 2007;11(6):429–438.

Yoon C, May CP, Hasher L. Aging, circadian arousal patterns, and cognition. In: Schwarz N, Park D, Knauper B, Sudman S, eds. Cognition, Aging, and Self-Reports. Philadelphia, Pennsylvania, USA: Psychology Press; 1999:117–143.

Broms U, et al. Long-term consistency of diurnal-type preferences among men. Chronobiol Int. 2014;31(2):182–188.

Wyatt JK, Ritz-De Cecco A, Czeisler CA, Dijk DJ. Circadian temperature and melatonin rhythms, sleep, and neurobehavioral function in humans living on a 20-h day. Am J Physiol. 1999;277(4 pt 2):R1152–R1163.

Schmidt C, Peigneux P, Cajochen C, Collette F. Adapting test timing to the sleep-wake schedule: effects on diurnal neurobehavioral performance changes in young evening and older morning chronotypes. Chronobiol Int. 2012;29(4):482–490.

May CP. Synchrony effects in cognition: the costs and a benefit. Psychon Bull Rev. 1999;6(1):142–147.

Hasher L, Goldstein D, May CP. It’s about time: circadian rhythms, memory, and aging. In: Izawa C, Ohta N, eds. Human Learning and Memory: Advances in Theory and Application: The 4th Tsukuba International Conference on Memory. Mahwah, New Jersey, USA: Lawrence Erlbaum Associates; 2005:199–217.

Monk TH, Buysse DJ, Reynolds CF, Kupfer DJ. Inducing jet lag in older people: adjusting to a 6-hour phase advance in routine. Exp Gerontol. 1993;28(2):119–133.

Monk TH, Buysse DJ, Carrier J, Kupfer DJ. Inducing jet-lag in older people: directional asymmetry. J Sleep Res. 2000;9(2):101–116.

Davidson AJ, Sellix MT, Daniel J, Yamazaki S, Menaker M, Block GD. Chronic jet-lag increases mortality in aged mice. Curr Biol. 2006;16(21):R914–R916.

Asai M, et al. Circadian profile of Per gene mRNA expression in the suprachiasmatic nucleus, paraventricular nucleus, and pineal body of aged rats. J Neurosci Res. 2001;66(6):1133–1139.

Kolker DE, Fukuyama H, Huang DS, Takahashi JS, Horton TH, Turek FW. Aging alters circadian and light-induced expression of clock genes in golden hamsters. J Biol Rhythms. 2003;18(2):159–169.

Zhang Y, Kornhauser JM, Zee PC, Mayo KE, Takahashi JS, Turek FW. Effects of aging on light-induced phase-shifting of circadian behavioral rhythms, fos expression and CREB phosphorylation in the hamster suprachiasmatic nucleus. Neuroscience. 1996;70(4):951–961.

Duffy JF, Zeitzer JM, Czeisler CA. Decreased sensitivity to phase-delaying effects of moderate intensity light in older subjects. Neurobiol Aging. 2007;28(5):799–807.

IARC Working Group on the Evaluation of Carcinogenic Risks to Humans. Painting, firefighting, and shiftwork. IARC Monogr Eval Carcinog Risks Hum. 2010;98:9–764.

Duffy JF, Dijk DJ, Klerman EB, Czeisler CA. Later endogenous circadian temperature nadir relative to an earlier wake time in older people. Am J Physiol. 1998;275(5 pt 2):R1478–R1487.

Duffy JF, Zeitzer JM, Rimmer DW, Klerman EB, Dijk DJ, Czeisler CA. Peak of circadian melatonin rhythm occurs later within the sleep of older subjects. Am J Physiol Endocrinol Metab. 2002;282(2):E297–E303.

Dijk DJ, Duffy JF, Czeisler CA. Contribution of circadian physiology and sleep homeostasis to age-related changes in human sleep. Chronobiol Int. 2000;17(3):285–311.

Hayashi Y, Endo S. All-night sleep polygraphic recordings of healthy aged persons: REM and slow-wave sleep. Sleep. 1982;5(3):277–283.

Zhdanova IV, Masuda K, Quasarano-Kourkoulis C, Rosene DL, Killiany RJ, Wang S. Aging of intrinsic circadian rhythms and sleep in a diurnal nonhuman primate, Macaca mulatta. J Biol Rhythms. 2011;26(2):149–159.

Naylor E, Buxton OM, Bergmann BM, Easton A, Zee PC, Turek FW. Effects of aging on sleep in the golden hamster. Sleep. 1998;21(7):687–693.

Koh K, Evans JM, Hendricks JC, Sehgal A. A Drosophila model for age-associated changes in sleep:wake cycles. Proc Natl Acad Sci U S A. 2006;103(37):13843–13847.

Van Cauter E, Leproult R, Plat L. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA. 2000;284(7):861–868.

Carskadon MA, Brown ED, Dement WC. Sleep fragmentation in the elderly: relationship to daytime sleep tendency. Neurobiol Aging. 1982;3(4):321–327.

Huang YL, Liu RY, Wang QS, Van Someren EJ, Xu H, Zhou JN. Age-associated difference in circadian sleep-wake and rest-activity rhythms. Physiol Behav. 2002;76(4–5):597–603.

Ohayon MM, Vecchierini MF. Daytime sleepiness and cognitive impairment in the elderly population. Arch Intern Med. 2002;162(2):201–208.

Stone KL, et al. Sleep disturbances and risk of falls in older community-dwelling men: the outcomes of Sleep Disorders in Older Men (MrOS Sleep) Study. J Am Geriatr Soc. 2014;62(2):299–305.

Borbély AA, Daan S, Wirz-Justice A, Deboer T. The two-process model of sleep regulation: a reappraisal. J Sleep Res. 2016;25(2):131–143.

Dijk DJ, Czeisler CA. Contribution of the circadian pacemaker and the sleep homeostat to sleep propensity, sleep structure, electroencephalographic slow waves, and sleep spindle activity in humans. J Neurosci. 1995;15(5 pt 1):3526–3538.

Schmidt C, Peigneux P, Cajochen C. Age-related changes in sleep and circadian rhythms: impact on cognitive performance and underlying neuroanatomical networks. Front Neurol. 2012;3:118.

Refinetti R, Menaker M. The circadian rhythm of body temperature. Physiol Behav. 1992;51(3):613–637.

Czeisler CA, et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science. 1999;284(5423):2177–2181.

Czeisler CA, et al. Association of sleep-wake habits in older people with changes in output of circadian pacemaker. Lancet. 1992;340(8825):933–936.

Vitiello MV, Smallwood RG, Avery DH, Pascualy RA, Martin DC, Prinz PN. Circadian temperature rhythms in young adult and aged men. Neurobiol Aging. 1986;7(2):97–100.

Monk TH, Buysse DJ, Reynolds CF 3rd, Kupfer DJ, Houck PR. Circadian temperature rhythms of older people. Exp Gerontol. 1995;30(5):455–474.

Touitou Y, Haus E. Alterations with aging of the endocrine and neuroendocrine circadian system in humans. Chronobiol Int. 2000;17(3):369–390.

Arendt J. Melatonin and human rhythms. Chronobiol Int. 2006;23(1–2):21–37.

Pack W, Hill DD, Wong KY. Melatonin modulates M4-type ganglion-cell photoreceptors. Neuroscience. 2015;303:178–188.

Kennaway DJ, Lushington K, Dawson D, Lack L, van den Heuvel C, Rogers N. Urinary 6-sulfatoxymelatonin excretion and aging: new results and a critical review of the literature. J Pineal Res. 1999;27(4):210–220.

Zhao ZY, Xie Y, Fu YR, Bogdan A, Touitou Y. Aging and the circadian rhythm of melatonin: a cross-sectional study of Chinese subjects 30–110 yr of age. Chronobiol Int. 2002;19(6):1171–1182.

Touitou Y, et al. Age- and mental health-related circadian rhythms of plasma levels of melatonin, prolactin, luteinizing hormone and follicle-stimulating hormone in man. J Endocrinol. 1981;91(3):467–475.

Reiter RJ, Richardson BA, Johnson LY, Ferguson BN, Dinh DT. Pineal melatonin rhythm: reduction in aging Syrian hamsters. Science. 1980;210(4476):1372–1373.

Zeitzer JM, Daniels JE, Duffy JF, et al. Do plasma melatonin concentrations decline with age? Am J Med. 1999;107(5):432–436.

Kin NM, Nair NP, Schwartz G, Thavundayil JX, Annable L. Secretion of melatonin in healthy elderly subjects: a longitudinal study. Ann N Y Acad Sci. 2004;1019:326–329.

Waller KL, et al. Melatonin and cortisol profiles in late midlife and their association with age-related changes in cognition. Nat Sci Sleep. 2016;8:47–53.

Wu YH, Zhou JN, Van Heerikhuize J, Jockers R, Swaab DF. Decreased MT1 melatonin receptor expression in the suprachiasmatic nucleus in aging and Alzheimer’s disease. Neurobiol Aging. 2007;28(8):1239–1247.

Videnovic A, et al. Circadian melatonin rhythm and excessive daytime sleepiness in Parkinson disease. JAMA Neurol. 2014;71(4):463–469.

Wu YH, et al. Molecular changes underlying reduced pineal melatonin levels in Alzheimer disease: alterations in preclinical and clinical stages. J Clin Endocrinol Metab. 2003;88(12):5898–5906.

Videnovic A, Lazar AS, Barker RA, Overeem S. ‘The clocks that time us’ — circadian rhythms in neurodegenerative disorders. Nat Rev Neurol. 2014;10(12):683–693.

Videnovic A, Zee PC. Consequences of Circadian Disruption on Neurologic Health. Sleep Med Clin. 2015;10(4):469–480.

Oster H, et al. The circadian rhythm of glucocorticoids is regulated by a gating mechanism residing in the adrenal cortical clock. Cell Metab. 2006;4(2):163–173.

Cuesta M, Cermakian N, Boivin DB. Glucocorticoids entrain molecular clock components in human peripheral cells. FASEB J. 2015;29(4):1360–1370.

Amir S, Lamont EW, Robinson B, Stewart J. A circadian rhythm in the expression of PERIOD2 protein reveals a novel SCN-controlled oscillator in the oval nucleus of the bed nucleus of the stria terminalis. J Neurosci. 2004;24(4):781–790.

Segall LA, Perrin JS, Walker CD, Stewart J, Amir S. Glucocorticoid rhythms control the rhythm of expression of the clock protein, Period2, in oval nucleus of the bed nucleus of the stria terminalis and central nucleus of the amygdala in rats. Neuroscience. 2006;140(3):753–757.

Balsalobre A, et al. Resetting of circadian time in peripheral tissues by glucocorticoid signaling. Science. 2000;289(5488):2344–2347.

Ohmori K, et al. Circadian rhythms and the effect of glucocorticoids on expression of the clock gene period1 in canine peripheral blood mononuclear cells. Vet J. 2013;196(3):402–407.

Touitou Y, et al. Adrenal circadian system in young and elderly human subjects: a comparative study. J Endocrinol. 1982;93(2):201–210.

Van Cauter E, Leproult R, Kupfer DJ. Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol. J Clin Endocrinol Metab. 1996;81(7):2468–2473.

Sherman B, Wysham C, Pfohl B. Age-related changes in the circadian rhythm of plasma cortisol in man. J Clin Endocrinol Metab. 1985;61(3):439–443.

Breen DP, et al. Sleep and circadian rhythm regulation in early Parkinson disease. JAMA Neurol. 2014;71(5):589–595.

Hartmann A, Veldhuis JD, Deuschle M, Standhardt H, Heuser I. Twenty-four hour cortisol release profiles in patients with Alzheimer’s and Parkinson’s disease compared to normal controls: ultradian secretory pulsatility and diurnal variation. Neurobiol Aging. 1997;18(3):285–289.

Hatfield CF, Herbert J, van Someren EJ, Hodges JR, Hastings MH. Disrupted daily activity/rest cycles in relation to daily cortisol rhythms of home-dwelling patients with early Alzheimer’s dementia. Brain. 2004;127(Pt 5):1061–1074.

Wijsman CA, et al. Ambulant 24-h glucose rhythms mark calendar and biological age in apparently healthy individuals. Aging Cell. 2013;12(2):207–213.

Singh R, Sharma S, Singh RK, Cornelissen G. Circadian time structure of circulating plasma lipid components in healthy indians of different age groups. Indian J Clin Biochem. 2016;31(2):215–223.

Luo W, et al. Old flies have a robust central oscillator but weaker behavioral rhythms that can be improved by genetic and environmental manipulations. Aging Cell. 2012;11(3):428–438.

Yamazaki S, Straume M, Tei H, Sakaki Y, Menaker M, Block GD. Effects of aging on central and peripheral mammalian clocks. Proc Natl Acad Sci U S A. 2002;99(16):10801–10806.

Sohail S, Yu L, Bennett DA, Buchman AS, Lim AS. Irregular 24-hour activity rhythms and the metabolic syndrome in older adults. Chronobiol Int. 2015;32(6):802–813.

Scheiermann C, Kunisaki Y, Frenette PS. Circadian control of the immune system. Nat Rev Immunol. 2013;13(3):190–198.

Nguyen KD, Fentress SJ, Qiu Y, Yun K, Cox JS, Chawla A. Circadian gene Bmal1 regulates diurnal oscillations of Ly6C(hi) inflammatory monocytes. Science. 2013;341(6153):1483–1488.

Deleidi M, Jäggle M, Rubino G. Immune aging, dysmetabolism, and inflammation in neurological diseases. Front Neurosci. 2015;9:172.

Chen CY, et al. Effects of aging on circadian patterns of gene expression in the human prefrontal cortex. Proc Natl Acad Sci U S A. 2016;113(1):206–211.

Ando H, et al. Influence of age on clock gene expression in peripheral blood cells of healthy women. J Gerontol A Biol Sci Med Sci. 2010;65(1):9–13.

Nakamura TJ, et al. Age-related changes in the circadian system unmasked by constant conditions(1,2,3). eNeuro. 2015;2(4):(4).

Kolker DE, Vitaterna MH, Fruechte EM, Takahashi JS, Turek FW. Effects of age on circadian rhythms are similar in wild-type and heterozygous Clock mutant mice. Neurobiol Aging. 2004;25(4):517–523.

Bonaconsa M, Malpeli G, Montaruli A, Carandente F, Grassi-Zucconi G, Bentivoglio M. Differential modulation of clock gene expression in the suprachiasmatic nucleus, liver and heart of aged mice. Exp Gerontol. 2014;55:70–79.

Marcheva B, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature. 2010;466(7306):627–631.

Papagiannakopoulos T, et al. Circadian rhythm disruption promotes lung tumorigenesis. Cell Metab. 2016;24(2):324–331.

Kondratov RV, Kondratova AA, Gorbacheva VY, Vykhovanets OV, Antoch MP. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev. 2006;20(14):1868–1873.

Krishnan N, Kretzschmar D, Rakshit K, Chow E, Giebultowicz JM. The circadian clock gene period extends healthspan in aging Drosophila melanogaster. Aging (Albany NY). 2009;1(11):937–948.

Nakahata Y, Sahar S, Astarita G, Kaluzova M, Sassone-Corsi P. Circadian control of the NAD+ salvage pathway by CLOCK-SIRT1. Science. 2009;324(5927):654–657.

Hurd MW, Ralph MR. The significance of circadian organization for longevity in the golden hamster. J Biol Rhythms. 1998;13(5):430–436.

Cai A, Scarbrough K, Hinkle DA, Wise PM. Fetal grafts containing suprachiasmatic nuclei restore the diurnal rhythm of CRH and POMC mRNA in aging rats. Am J Physiol. 1997;273(5 pt 2):R1764–R1770.

Li H, Satinoff E. Fetal tissue containing the suprachiasmatic nucleus restores multiple circadian rhythms in old rats. Am J Physiol. 1998;275(6 pt 2):R1735–R1744.

Swaab DF, Fliers E, Partiman TS. The suprachiasmatic nucleus of the human brain in relation to sex, age and senile dementia. Brain Res. 1985;342(1):37–44.

Zhou JN, Swaab DF. Activation and degeneration during aging: a morphometric study of the human hypothalamus. Microsc Res Tech. 1999;44(1):36–48.

Tsukahara S, Tanaka S, Ishida K, Hoshi N, Kitagawa H. Age-related change and its sex differences in histoarchitecture of the hypothalamic suprachiasmatic nucleus of F344/N rats. Exp Gerontol. 2005;40(3):147–155.

Madeira MD, Sousa N, Santer RM, Paula-Barbosa MM, Gundersen HJ. Age and sex do not affect the volume, cell numbers, or cell size of the suprachiasmatic nucleus of the rat: an unbiased stereological study. J Comp Neurol. 1995;361(4):585–601.

Hofman MA, Swaab DF. Alterations in circadian rhythmicity of the vasopressin-producing neurons of the human suprachiasmatic nucleus (SCN) with aging. Brain Res. 1994;651(1-2):134–142.

Zhou JN, Hofman MA, Swaab DF. VIP neurons in the human SCN in relation to sex, age, and Alzheimer’s disease. Neurobiol Aging. 1995;16(4):571–576.

Chee CA, Roozendaal B, Swaab DF, Goudsmit E, Mirmiran M. Vasoactive intestinal polypeptide neuron changes in the senile rat suprachiasmatic nucleus. Neurobiol Aging. 1988;9(3):307–312.

Roozendaal B, van Gool WA, Swaab DF, Hoogendijk JE, Mirmiran M. Changes in vasopressin cells of the rat suprachiasmatic nucleus with aging. Brain Res. 1987;409(2):259–264.

Cayetanot F, Bentivoglio M, Aujard F. Arginine-vasopressin and vasointestinal polypeptide rhythms in the suprachiasmatic nucleus of the mouse lemur reveal aging-related alterations of circadian pacemaker neurons in a non-human primate. Eur J Neurosci. 2005;22(4):902–910.

Wang JL, et al. Suprachiasmatic neuron numbers and rest-activity circadian rhythms in older humans. Ann Neurol. 2015;78(2):317–322.

Vasalou C, Herzog ED, Henson MA. Small-world network models of intercellular coupling predict enhanced synchronization in the suprachiasmatic nucleus. J Biol Rhythms. 2009;24(3):243–254.

Palomba M, Nygård M, Florenzano F, Bertini G, Kristensson K, Bentivoglio M. Decline of the presynaptic network, including GABAergic terminals, in the aging suprachiasmatic nucleus of the mouse. J Biol Rhythms. 2008;23(3):220–231.

Aton SJ, Huettner JE, Straume M, Herzog ED. GABA and Gi/o differentially control circadian rhythms and synchrony in clock neurons. Proc Natl Acad Sci U S A. 2006;103(50):19188–19193.

Satinoff E, et al. Do the suprachiasmatic nuclei oscillate in old rats as they do in young ones? Am J Physiol. 1993;265(5 pt 2):R1216–R1222.

Watanabe A, Shibata S, Watanabe S. Circadian rhythm of spontaneous neuronal activity in the suprachiasmatic nucleus of old hamster in vitro. Brain Res. 1995;695(2):237–239.

Nakamura TJ, et al. Age-related decline in circadian output. J Neurosci. 2011;31(28):10201–10205.

Farajnia S, et al. Evidence for neuronal desynchrony in the aged suprachiasmatic nucleus clock. J Neurosci. 2012;32(17):5891–5899.

Nakamura TJ, Takasu NN, Nakamura W. The suprachiasmatic nucleus: age-related decline in biological rhythms. J Physiol Sci. 2016;66(5):367–374.

Gavrila AM, Robinson B, Hoy J, Stewart J, Bhargava A, Amir S. Double-stranded RNA-mediated suppression of Period2 expression in the suprachiasmatic nucleus disrupts circadian locomotor activity in rats. Neuroscience. 2008;154(2):409–414.

Izumo M, et al. Differential effects of light and feeding on circadian organization of peripheral clocks in a forebrain Bmal1 mutant. Elife. 2014;:3.

Banks G, Nolan PM, Peirson SN. Reciprocal interactions between circadian clocks and aging. Mamm Genome. 2016;27(7–8):332–340.

McDearmon EL, et al. Dissecting the functions of the mammalian clock protein BMAL1 by tissue-specific rescue in mice. Science. 2006;314(5803):1304–1308.

Yang G, et al. Timing of expression of the core clock gene Bmal1 influences its effects on aging and survival. Sci Transl Med. 2016;8(324):324ra16.

Chang HC, Guarente L. SIRT1 mediates central circadian control in the SCN by a mechanism that decays with aging. Cell. 2013;153(7):1448–1460.

Finkel T, Deng CX, Mostoslavsky R. Recent progress in the biology and physiology of sirtuins. Nature. 2009;460(7255):587–591.

Nakahata Y, et al. The NAD+-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell. 2008;134(2):329–340.

Asher G, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell. 2008;134(2):317–328.

Wang RH, et al. Negative reciprocal regulation between Sirt1 and Per2 modulates the circadian clock and aging. Sci Rep. 2016;6:28633.

Valentinuzzi VS, Scarbrough K, Takahashi JS, Turek FW. Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice. Am J Physiol. 1997;273(6 pt 2):R1957–R1964.

Scheuermaier K, Laffan AM, Duffy JF. Light exposure patterns in healthy older and young adults. J Biol Rhythms. 2010;25(2):113–122.

Shochat T, Martin J, Marler M, Ancoli-Israel S. Illumination levels in nursing home patients: effects on sleep and activity rhythms. J Sleep Res. 2000;9(4):373–379.

Kessel L, Lundeman JH, Herbst K, Andersen TV, Larsen M. Age-related changes in the transmission properties of the human lens and their relevance to circadian entrainment. J Cataract Refract Surg. 2010;36(2):308–312.

Hattar S, et al. Melanopsin and rod-cone photoreceptive systems account for all major accessory visual functions in mice. Nature. 2003;424(6944):76–81.

Hattar S, Liao HW, Takao M, Berson DM, Yau KW. Melanopsin-containing retinal ganglion cells: architecture, projections, and intrinsic photosensitivity. Science. 2002;295(5557):1065–1070.

Kessel L, Siganos G, Jørgensen T, Larsen M. Sleep disturbances are related to decreased transmission of blue light to the retina caused by lens yellowing. Sleep. 2011;34(9):1215–1219.

Herbst K, et al. Intrinsically photosensitive retinal ganglion cell function in relation to age: a pupillometric study in humans with special reference to the age-related optic properties of the lens. BMC Ophthalmol. 2012;12:4.

Kankipati L, Girkin CA, Gamlin PD. Post-illumination pupil response in subjects without ocular disease. Invest Ophthalmol Vis Sci. 2010;51(5):2764–2769.

Asplund R, Lindblad BE. Sleep and sleepiness 1 and 9 months after cataract surgery. Arch Gerontol Geriatr. 2004;38(1):69–75.

Ayaki M, Muramatsu M, Negishi K, Tsubota K. Improvements in sleep quality and gait speed after cataract surgery. Rejuvenation Res. 2013;16(1):35–42.

Brøndsted AE, Lundeman JH, Kessel L. Short wavelength light filtering by the natural human lens and IOLs — implications for entrainment of circadian rhythm. Acta Ophthalmol. 2013;91(1):52–57.

Brøndsted AE, et al. The effect of cataract surgery on circadian photoentrainment: a randomized trial of blue-blocking versus neutral intraocular lenses. Ophthalmology. 2015;122(10):2115–2124.

Yan SS, Wang W. The effect of lens aging and cataract surgery on circadian rhythm. Int J Ophthalmol. 2016;9(7):1066–1074.

Stephan FK. The “other” circadian system: food as a Zeitgeber. J Biol Rhythms. 2002;17(4):284–292.

Damiola F, Le Minh N, Preitner N, Kornmann B, Fleury-Olela F, Schibler U. Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. Genes Dev. 2000;14(23):2950–2961.

Mistlberger RE, Houpt TA, Moore-Ede MC. Effects of aging on food-entrained circadian rhythms in the rat. Neurobiol Aging. 1990;11(6):619–624.

Walcott EC, Tate BA. Entrainment of aged, dysrhythmic rats to a restricted feeding schedule. Physiol Behav. 1996;60(5):1205–1208.

Boulos Z, Rosenwasser AM, Terman M. Feeding schedules and the circadian organization of behavior in the rat. Behav Brain Res. 1980;1(1):39–65.

Kent BA. Synchronizing an aging brain: can entraining circadian clocks by food slow Alzheimer’s disease? Front Aging Neurosci. 2014;6:234.

Katewa SD, et al. Peripheral circadian clocks mediate dietary restriction-dependent changes in lifespan and fat metabolism in Drosophila. Cell Metab. 2016;23(1):143–154.

Sellix MT, et al. Aging differentially affects the re-entrainment response of central and peripheral circadian oscillators. J Neurosci. 2012;32(46):16193–16202.

Tahara Y, et al. In vivo monitoring of peripheral circadian clocks in the mouse. Curr Biol. 2012;22(11):1029–1034.

Wyse CA, Coogan AN, Selman C, Hazlerigg DG, Speakman JR. Association between mammalian lifespan and circadian free-running period: the circadian resonance hypothesis revisited. Biol Lett. 2010;6(5):696–698.

Libert S, Bonkowski MS, Pointer K, Pletcher SD, Guarente L. Deviation of innate circadian period from 24 h reduces longevity in mice. Aging Cell. 2012;11(5):794–800.

Jones SE, et al. Genome-wide association analyses in 128,266 individuals identifies new morningness and sleep duration loci. PLoS Genet. 2016;12(8):e1006125.
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