Skip to main content

Aging of the Mammalian Circadian System

  • Chapter
Circadian Clocks

Abstract

Numerous studies have demonstrated that as animals reach advanced age for the species, there are pronounced changes in the expression of diverse circadian rhythms. Many of the observed changes may reflect an overall deterioration of the health of the organism. On the other hand, changes in the circadian system may not simply reflect such deterioration, but may represent one of the underlying causes for the negative health effects associated with advanced age. Most studies of the effects of advanced age on the circadian system have been carried out on rodents and humans. Since Chapter 22 of this volume reviews the literature on the effects of aging on the human circadian system, this chapter will focus primarily on studies of rodents, particularly the best-studied animals in this regard: laboratory rats, mice, and golden (Syrian) hamsters. After first describing the multitude of changes that have been observed in the aging circadian system of rodents, this review will [1] examine the underlying physiologic mechanisms that lead to these changes, [2] provide an overview of attempts to attenuate or reverse age-related effects on circadian rhythmicity, and [3] speculate on the functional significance of such changes.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 249.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Arendt, J. (1994). The pineal gland: Basic physiology and clinical implications. In L. J. DeGroot (Ed.), Endocrinology (pp. 432–444). Philadelphia: Saunders.

    Google Scholar 

  • Armstrong, S. M., & Redman, J. R. (1991). Melatonin: A chronobiotic with anti-aging properties? Medical Hypotheses, 34, 300–309.

    PubMed  CAS  Google Scholar 

  • Aschoff, J., Fatranska, M., Giedke, H., Doerr, P., Stamm, D., & Wisser, H. (1971). Human circadian rhythms in continuous darkness: Entrainment by social cues. Science, 171, 213–215.

    PubMed  CAS  Google Scholar 

  • Bahr, B. A., Godshall, A. C., Hall, R. A., & Lynch, G. (1992). Mouse telencephalon exhibits an age-related decrease in glutamate (AMPA) receptors but no change in nerve terminal markers. Brain Research, 589, 320–326.

    PubMed  CAS  Google Scholar 

  • Brock, M. A. (1991). Chronobiology and aging. Journal of the American Geriatrics Society, 39, 74–91.

    PubMed  CAS  Google Scholar 

  • Cai, A., Lehman, M. N., Lloyd, J. M., & Wise, P. M. (1997). Transplantation of fetal suprachiasmatic nuclei into middle-aged rats restores diurnal Fos expression in host. American Journal of Physiology, 272, R422–R428.

    PubMed  CAS  Google Scholar 

  • Cao, V. H., Edgar, D. M., Heller, H. C., Dement, W. C., & Miller, J. D. (1995). Basal and phase-shifted neuronal rhythms in the aged SCN in vitro. Society for Neuroscience, Abstracts, 21, 1235.

    Google Scholar 

  • Chee, C. A., Roozendaal, B., Swaab, D. F., Goudsmit, E., & Mirmiran, M. (1988). Vasoactive intestinal polypeptide neuron changes in the senile rat suprachiasmatic nucleus. Neurobiology of Aging, 9, 307–312.

    PubMed  CAS  Google Scholar 

  • Czeisler, C. A., Kronauer, R. E., Allan, J. S., Duffy, J. F., Jewett, M. E., Brown, E. N., & Ronda, J. M. (1989). Bright light induction of strong (type 0) resetting of the human circadian pacemaker. Science, 244, 1328–1333.

    PubMed  CAS  Google Scholar 

  • Czeisler, C. A., Chiasera, A. J., & Duffy, J. F. (1991). Research on sleep, circadian rhythms and aging: Applications to manned spaceflight. Experimental Gerontology, 26, 217–232.

    PubMed  CAS  Google Scholar 

  • Czeisler, C. A., Kronauer, R. E., & Allan, J S (1992). Assessment of modification of a subject’s endogenous circadian cycle. U.S. Patent No. 5,163–426.

    Google Scholar 

  • Davidoff, M. S., & Lolova, I. S. (1991). Age-related changes in the serotonin immunoreactivity in the telencephalon and diencephalon of rats. Journal für Hirnforschung, 32, 745–753.

    PubMed  CAS  Google Scholar 

  • Davis, F. C., & Menaker, M. (1980). Hamsters through time’s window: Temporal structure of hamster locomotor rhythmicity. American Journal of Physiology, 239, R149–R155.

    PubMed  CAS  Google Scholar 

  • Dawson, D., & Encel, N. (1993). Melatonin and sleep in humans Journal of Pineal Research, 15, 1–12.

    PubMed  CAS  Google Scholar 

  • Dollins, A. B., Zhdanova, I. V., Wurtman, R J, Lynch, H. J., & Deng, M. H. (1994). Effect of inducing nocturnal serum melatonin concentrations in daytime on sleep, mood, body temperature, and performance. Proceedings of the National Academy of Sciences of the USA, 91, 1824–1828.

    Google Scholar 

  • Dubocovich, M. L., Benloucif, S., & Masana, M. I. (1996). Melatonin receptors in the mammalian suprachiasmatic nucleus. Behavioural Brain Research, 73, 141–147.

    PubMed  CAS  Google Scholar 

  • Duncan, M. J., & Purvis, C. C. (1994). Effects of aging on photoperiodic responsiveness and specific 2-[1251]-iodomelatonin binding sites in the pars tuberalis and suprachiasmatic nuclei of Siberian hamsters. Journal of Pineal Research, 16, 184–187.

    PubMed  CAS  Google Scholar 

  • Ebihara, S., Marks, T., Hudson, D.J., Sc Menaker, M. (1986). Genetic control of melatonin synthesis in the pineal gland of the mouse. Science, 231, 491–493.

    PubMed  CAS  Google Scholar 

  • Grad, B. R., & Rozencwaig, R. (1993). The role of melatonin and serotonin in aging: Update. Psychoneuroendocrinology, 18, 283–295.

    PubMed  CAS  Google Scholar 

  • Halberg, J., Halberg, E., Regal, P., & Halberg, F. (1981). Changes with age characterize circadian rhythm in telemetered core temperature of stroke prone rats. Journal of Gerontology, 36, 28–30.

    PubMed  CAS  Google Scholar 

  • Hofman, M. A., & Swaab, D. F. (1994). Alterations in circadian rhythmicity of the vasopressin-producing neurons of the human suprachiasmatic nucleus (SCN) with aging. Brain Research, 651, 134–142.

    PubMed  CAS  Google Scholar 

  • Hofman, M., & Swaab, D. (1995). Influence of aging on the seasonal rhythm of the vasopressin-expressing neurons in the human suprachiasmatic nucleus. Neurobiology of Aging, 16, 965–971.

    PubMed  CAS  Google Scholar 

  • Humbert, W., & Pevet, P. (1994). The decrease of pineal melatonin production with age. Annals of the New York Academy of Sciences, 719, 43–63.

    PubMed  CAS  Google Scholar 

  • Hurd, M. W., Zimmer, K. A., Lehman, M. N., & Ralph, M. R. (1995). Circadian locomotor rhythms in aged hamsters following suprachiasmatic transplant. American Journal of Physiology, 269, R958–R968.

    PubMed  CAS  Google Scholar 

  • Illnerova, H. (1991). The suprachiasmatic nucleus and rhythmic pineal melatonin production. In D. C. Klein, R. Y. Moore, & S. M. Reppert (Eds.), Suprachiasmatic nucleus-The mind’s clock (pp. 197–216). New York: Oxford University Press.

    Google Scholar 

  • King, D. P., Zhao, Y., Sangoram, A. M., Wilsbacher, L. D., Tanaka, M., Antoch, M. P., Steeves, T. D. L., Vitaterna, M. H., Kornhauser, J. M., Lowery, P. L., Turek, F. W., & Takahashi, J. S. (1997). Positional cloning of the mouse circadian Clock gene. Cell, 89, 641–653.

    PubMed  CAS  Google Scholar 

  • Kornhauser, J. M., Nelson, D. E., Mayo, K. E., & Takahashi, J. S. (1990). Photic and circadian regulation of c-fos gene expression in the hamster suprachiasmatic nucleus. Neuron, 5, 127–134.

    PubMed  CAS  Google Scholar 

  • Koster-van Hoffen, G. C., Mirmiran, M., Bos, N. P., Witting, W., Delagrange, P., & Guardiola-Lemaitre, B. (1993). Effects of a novel melatonin analog on circadian rhythms of body temperature and activity in young, middle-aged, and old rats. Neurobiology of Aging, 14, 565–569.

    PubMed  CAS  Google Scholar 

  • Laartz, B., Losee-Olson, S., Ge, Y.-R., & Turek, F. W. (1994). Diurnal, photoperiodic and age-related changes in plasma growth hormone levels in the golden hamster. Journal of Biological Rhythms, 9, 111–123.

    PubMed  CAS  Google Scholar 

  • Labyak, S. E., Zee, P. C., Wallen, E. P., & Turek, F. W. (1996). An evaluation of circadian locomotor activity in young, middle aged, and old golden hamsters. Society for Research on Biological Rhythms, Abstracts, 173, 113.

    Google Scholar 

  • Labyak, S. E., Turek, F. W., Wallen, E. P., & Zee, P. C. (1998). The effects of bright light on age-related changes in the locomotor activity of Syrian hamsters. American Journal of Physiology, 274, R830–R839.

    PubMed  CAS  Google Scholar 

  • Lavie, P. (1997). Melatonin: Role in gating nocturnal rise in sleep propensity. Journal of Biological Rhythms,12, 657–665.

    PubMed  CAS  Google Scholar 

  • Lehman, M. N., Silver, R, Gladstone, W. R., Kahn, R. M., Gibson, M., & Bittman, E. L. (1987). Circadian rhythmicity restored by neural transplant: Immunocytochemical characterization of the graft and its integration with the host brain. Journal of Neuroscience, 7, 1626–1638.

    PubMed  CAS  Google Scholar 

  • Martin, J. R., Fuchs, A., Bender, R., & Harting, J. (1985). Altered light-dark activity difference with aging in two rat strains. Journal of Gerontology, 44, 2–7.

    Google Scholar 

  • Martin, P., & Bateson, P. (1997). Measuring behaviour: An introductory guide. Cambridge: Cambridge University Press.

    Google Scholar 

  • McArthur, A. J., Gillette, M. U., & Prosser, R. A. (1991). Melatonin directly resets the rat suprachiasmatic circadian clock in vitro. Brain Research, 565, 158–161.

    PubMed  CAS  Google Scholar 

  • Meites, J. (1991). Role of hypothalamic catecholamines in aging processes. Acta Endocrinologica, 125, 98–103.

    PubMed  CAS  Google Scholar 

  • Menaker, M., & Refinetti, R. (1992). The tau mutation in golden hamsters. In M. Young (Ed.), Molecular genetics of biological rhythms (pp. 255–269). New York: Marcel Dekker.

    Google Scholar 

  • Miller, A. E., & Riegle, G. D. (1982). Temporal patterns of serum luteinizing hormone and testosterone and endocrine response to luteinizing hormone in aging male rats. Journal of Gerontology, 37, 522–528.

    PubMed  CAS  Google Scholar 

  • Miller, J. D., Morin, L. P., Schwartz, W. J., & Moore, R Y. (1996). New insights into the mammalian circadian clock. Sleep, 19, 641–667.

    PubMed  CAS  Google Scholar 

  • Monk, T. H., Buysse, D. J., Reynolds, C. E I., & Kupfer, D. J. (1993). Inducing jet lag in older people: Adjusting to a 6-hour phase advance in routine. Experimental Gerontology, 28, 119–133.

    PubMed  CAS  Google Scholar 

  • Moore, R. Y. (1996). Neural control of the pineal gland. Behavioural Brain Research, 73, 125–130.

    Google Scholar 

  • Morgan, P. J., Howell, H. E., & Helliwell, R. (1994). Melatonin receptors: Localization, molecular pharmacology and physiological significance. Neurochemistry International, 24, 101–146.

    PubMed  CAS  Google Scholar 

  • Morin, L. P. (1988). Age-related changes in hamster circadian period, entrainment and rhythm splitting.Journal of Biological Rhythms, 3, 237–248.

    Google Scholar 

  • Morin, L. P., & Blanchard, J. (1991). Depletion of brain serotonin by 5,7-DHT modifies hamster circadian rhythm response to light. Brain Research, 566, 173–185.

    PubMed  CAS  Google Scholar 

  • Mosko, S. S., Erickson, G. F., & Moore, R. Y. (1980). Dampened circadian rhythms in reproductively senescent female rats. Behavioral Neural Biology, 28, 1–14.

    CAS  Google Scholar 

  • Mrosovsky, N. (1996). Locomotor activity and non-photic influences on circadian clocks. Biological Reviews of the Cambridge Philosophical Society, 71, 343–372.

    PubMed  CAS  Google Scholar 

  • Mrosovsky, N., Reebs, S. G., Honrado, G. I., & Salmon, P. A. (1989). Behavioural entrainment of circadian rhythms. Experientia, 45, 696–702.

    PubMed  CAS  Google Scholar 

  • Myers, B. L., & Badia, P. (1995). Changes in circadian rhythms and sleep quality with aging: Mechanisms and interventions. Neuroscience and Biobehavioral Reviews, 19, 553–571.

    PubMed  CAS  Google Scholar 

  • Nelson, W., & Halberg, E (1986). Schedule-shifts, circadian rhythms and lifespan of freely-feeding and meal-fed mice. Physiology and Behavior, 38, 781.

    PubMed  CAS  Google Scholar 

  • Nicolau, G. Y., & Milcu, S. (1977). Circadian rhythm of corticosterone and nucleic acids in the rat adrenals in relation to age. Chronobiologia, 4, 136.

    Google Scholar 

  • Penev, P. D., Turek, E W., & Zee, P. C. (1993). Monoamine depletion alters the entrainment and the response to light of the circadian activity rhythm in hamsters. Brain Research, 612, 156–164.

    PubMed  CAS  Google Scholar 

  • Penev, P. D., Zee, P. C., & Turek, F. W. (1994). Reserpine abolishes the phase-shifting effect of triazolam on locomotor activity rhythms of golden hamsters. Brain Research, 637, 255–261.

    PubMed  CAS  Google Scholar 

  • Penev, P. D., Zee, P. C., Wallen, E. P., & Turek, F. W. (1995). Aging alters the phase-resetting properties of a serotonin agonist on hamster circadian rhythmicity. American Journal of Physiology, 268, R293—R298.

    PubMed  Google Scholar 

  • Penev, P. D., Turek, F. W., Wallen, E. P., & Zee, P. C. (1997a). Aging alters the serotonergic modulation of light-induced phase advances in golden hamsters. American Journal of Physiology, 272, R509—R513.

    PubMed  Google Scholar 

  • Penev, P. D., Zee, P. C., & Turek, E W. (1997b). Quantitative analysis of the age-related fragmentation of hamster 24-h activity rhythms. American Journal of Physiology, 273, R2132—R2137.

    PubMed  Google Scholar 

  • Peng, M. T, & Rang, M. (1984). Circadian rhythms and patterns of running-wheel activity, feeding and drinking behaviors of old male rats. Physiology and Behavior, 33, 615–620.

    PubMed  CAS  Google Scholar 

  • Peng, M. T., Jiang, M.J., & Hsu, H. K. (1980). Changes in running-wheel activity, eating and drinking and their day/night distribution throughout the life span of the rat. Journal of Gerontology, 35, 339–347.

    PubMed  CAS  Google Scholar 

  • Pierpaoli, W., & Regelson, W. (1994). Pineal control of aging: Effect of melatonin and pineal grafting on aging mice. Proceedings of the National Academy of Sciences of the USA, 94, 787–791.

    Google Scholar 

  • Pittendrigh, C. S. (1974). Circadian oscillations in cells and the circadian organization of multicellular systems. In E C. Schmitt & E G. Worden (Eds.), The neurosciences, third study program (pp. 437–458). Cambridge, MA: MIT Press.

    Google Scholar 

  • Pittendrigh, C. S., & Daan, S. (1974). Circadian oscillations in rodents: A systematic increase of their frequency with age. Science, 186, 548–550.

    PubMed  CAS  Google Scholar 

  • Pittendrigh, C. S, & Daan, S. (1976). A functional analysis of circadian pacemakers in nocturnal rodents. II. The variability of phase response curves. Journal of Comparative Physiology, 106, 253–266.

    Google Scholar 

  • Pittendrigh, C. S., & Minis, D. H. (1972). Circadian systems: Longevity as a function of circadian resonance in Drosophila melanogaster. Proceedings of the National Academy of Sciences of the USA, 69, 1537.

    PubMed  CAS  Google Scholar 

  • Possidente, B., McEldowney, S., & Pabon, A. (1995). Aging lengthens circadian period of wheel-running activity in C57BL mice. Physiology and Behavior, 57, 575–579.

    PubMed  CAS  Google Scholar 

  • Quay, W. B. (1972). Pineal homeostatic regulation of shifts in the circadian activity rhythm during maturation and aging. Transactions of the New York Academy of Sciences, 34, 239–254.

    PubMed  CAS  Google Scholar 

  • Ralph, M. R., & Menaker, M. (1988). A mutation of the circadian system in golden hamster. Science, 241,1225–1227.

    PubMed  CAS  Google Scholar 

  • Redman, J., Armstrong, S., & Ng, K. T. (1983). Free-running activity rhythms in the rat: Entrainment by melatonin. Science, 219, 1089–1091.

    PubMed  CAS  Google Scholar 

  • Reiter, R. J. (1992). The aging pineal gland and its physiological consequences. Bioessays, 14, 169–175.

    PubMed  CAS  Google Scholar 

  • Reiter, R. J. (1995). The pineal gland and melatonin in relation to aging: A summary of the theories and the data. Experimental Gerontology, 30, 199–212.

    PubMed  CAS  Google Scholar 

  • Reiter, R.J., Craft, C. M., Johnson, J. E., Jr., King, T S., Richardson, B. A., Vaughan, G. M., & Vaughan, M. K. (1981). Age associated reduction in nocturnal pineal melatonin levels in female rats. Endocrinology, 109, 1295–1297.

    PubMed  CAS  Google Scholar 

  • Reiter, R.J., Tan, D. X., Poeggeler, B., Menendez-Pelaez, A., Chen, L. D., & Saarela, S. (1994). Melatonin as a free radical scavenger: Implications for aging and age-related diseases. Annals of the New York Academy of Sciences, 719, 1–12.

    PubMed  CAS  Google Scholar 

  • Reppert, S. M., & Weaver, D. R. (1995). Melatonin madness. Cell, 83, 1059–1062.

    PubMed  CAS  Google Scholar 

  • Reynolds, C. E, III, Jennings, J. R., Hoch, C. C., Monk, T H., Berman, S. R., Hall, F. T, Matzzie, J. V., Buysse, D. J., & Kupfer, D. J. (1991). Daytime sleepiness in the healthy “old old”: A comparison with young adults. Journal of the American Geriatrics Society, 39, 957–962.

    PubMed  Google Scholar 

  • Richardson, G. S. (1990). Circadian rhythms and aging. In E. L. Schneider &J. W. Rowe (Eds.), Handbook of the biology of aging (pp. 275–305). San Diego, CA: Academic Press.

    Google Scholar 

  • Roozendaal, B., Van Gool, W. A., Swaab, D. F., Hoogendyk, J. E., & Mirmirian, M. (1987). Changes in vasopressin cells of the rat suprachiasmatic nucleus with aging. Brain Research, 409, 259–264.

    PubMed  CAS  Google Scholar 

  • Rosenberg, R. S., Zepelin, H., & Rechtschaffen, A. (1979). Sleep in young and old rats. journal of Gerontology, 34, 525–532.

    PubMed  CAS  Google Scholar 

  • Rosenberg, R. S., Winter, J., & Rechtschaffen, A. (1980). Effects of light cycle phase reversal on sleep rhythms of young and old rats. Sleep Research, 9, 105.

    Google Scholar 

  • Rosenberg, R. S., Zee, P. C., & Turek, F. W. (1991). Phase response curves to light in young and old hamsters. American journal of Physiology, 261, R491–R495.

    PubMed  CAS  Google Scholar 

  • Rusak, B., & Bina, K. G. (1990). Neurotransmitters in the mammalian circadian system. Annual Review of Neuroscience, 13, 387–401.

    PubMed  CAS  Google Scholar 

  • Sacher, G. A, & Duffy, P. H. (1978). Age changes in rhythms of energy metabolism, activity and body core temperature in Mus musculus and Peromyscus. In H. V. Samis & S. Copobianco (Eds.), Aging and biological rhythms (pp. 105–124). New York: Plenum Press.

    Google Scholar 

  • Sack, R. L., Lewy, A. J., Blood, M. L., & Stevenson, J. (1991). Melatonin administration to blind people: Phase advances and entrainment. journal of Biological Rhythms, 6, 249–261.

    PubMed  CAS  Google Scholar 

  • Saint Paul, U. V. (1978). Longevity among blowflies Phormia terraenovae R.D. kept in non-24 hour light-dark cycles. journal of Comparative Physiology, 127, 191.

    Google Scholar 

  • Satinoff, E., Sc Li, H. (1996). Fetal tissue containing the suprachiasmatic nucleus restores circadian rhythms in old rats. Society for Research on Biological Rhythms, Abstracts, 110, 82.

    Google Scholar 

  • Satinoff, E., Li, H., Tcheng, T. K, Liu, C., McArthur, A. J., Medanic, M., & Gillette, M. U. (1993). Do the suprachiasmitc nuclei oscillate in old rats as they do in young ones? American journal of Physiology, 265, R1216–R1222.

    PubMed  CAS  Google Scholar 

  • Scarbrough, K., & Turek, F. W. (1996). Quantitative differences in the circadian rhythm of locomotor activity and vasopressin and vasoactive intestinal peptide gene expression in the suprachiasmatic nucleus of tau mutant compared to wildtype hamsters. Brain Research, 736, 251–259.

    PubMed  CAS  Google Scholar 

  • Scarbrough, K, Losee-Olson, S., Wallen, E. P., & Turek, F. W. (1997). Aging and photoperiod effect on entrainment and quantitative aspects of locomotor behavior in Syrian hamsters. American journal of Physiology, 272, R1219–R1225.

    PubMed  CAS  Google Scholar 

  • Schmid, H. A. (1993). Decreased melatonin biosynthesis, calcium flux, pineal gland calcification and aging: A hypothetical framework. Gerontology, 39, 189–199.

    PubMed  CAS  Google Scholar 

  • Sheng, M., McFadden, G., & Greenberg, M. E. (1990). Membrane depolarization and calcium induce c-fos transcription via phosphorylation of transcription factor CREB. Neuron, 4, 571–582.

    PubMed  CAS  Google Scholar 

  • Shimomura, K, & Menaker, M. (1994). Light-induced phase shifts in tau mutant hamsters. Journal of Biological Rhythms, 9, 97–110.

    PubMed  CAS  Google Scholar 

  • Silver, R., LeSauter, J., Tresco, P. A., & Lehman, M. N. (1996). A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature, 382, 810–813.

    PubMed  CAS  Google Scholar 

  • Slater, P. J. B., & Lester, N. P. (1982). Minimising errors in splitting behaviour into bouts. Behaviour, 79,153–162.

    Google Scholar 

  • Smale, L., Michels, K. M., Moore, R. Y., & Morin, L. P. (1990). Destruction of the hamster serotoninergic system by 5,7-DHT: Effects on circadian rhythm phase, entrainment and response to triazolam. Brain Research, 515, 9–19.

    PubMed  CAS  Google Scholar 

  • Smith, D. O. (1988). Cellular and molecular correlates of aging in the nervous system. Experimental Gerontology, 23, 399–412.

    PubMed  CAS  Google Scholar 

  • Sumova, A., Maywood, E. S., Selvage, D., Ebling, F. J., & Hastings, M. (1996). Serotonergic antagonists impair arousal-induced phase shifts of the circadian system of the Syrian hamster. Brain Research, 709, 88–96.

    PubMed  CAS  Google Scholar 

  • Sutin, E. L., Dement, W. C., Heller, H. C., & Kilduff, T. S. (1993). Light-induced gene expression in the suprachiasmatic nucleus of young and aging rats. Neurobiology of Aging, 14, 441–446.

    PubMed  CAS  Google Scholar 

  • Swaab, D. F., Fisser, B., Kamphorst, W., & Troust, D. (1988). The human suprachiasmatic nucleus: Neuropeptide changes in senium and Alzheimer’s disease. Basic and Applied Histochemistry, 32, 43–54.

    PubMed  CAS  Google Scholar 

  • Tang, F., Hadjiconstantinov, M., & Pang, S. F. (1985). Aging and diurnal rhythms of pineal serotonin, 5-hydroxy-indoleacetic acid, norepinephrine, dopamine and serum melatonin in the rat. Neuroendocrinology, 40, 160–164.

    PubMed  CAS  Google Scholar 

  • Tenover, J. S., Matsumoto, A. M., Clifton, D. K, & Bremner, W. J. (1988). Age-related alterations in the circadian rhythm of pulsatile luteinizing hormone and testosterone secretion in healthy men. Journal of Gerontology, 43, 163–169.

    Google Scholar 

  • Turek, F. W. (1987). Pharmacological probes of the mammalian circadian clock: Use of the phase response curve approach. Trends in Pharmacological Science, 8, 212–217.

    CAS  Google Scholar 

  • Turek, E W. (1991). Introduction: Chapter IV, circadian SCN outputs. In D. C. Klein, R. Y. Moore, & S. M. Reppert (Eds.), Suprachiasmatic nucleus: The mind’s clock (pp. 191). New York: Oxford University Press.

    Google Scholar 

  • Turek, E W. (1996). Melatonin hype hard to swallow. Nature, 379, 295–296.

    PubMed  CAS  Google Scholar 

  • Turek, E W., & Gzeisler, C. A. (1998). Role of melatonin in the regulation of sleep. In F. W. Turek & P. C. Zee (Eds.), Neurobiology of sleep and circadian rhythms (pp. 181–195). New York: Marcel Dekker.

    Google Scholar 

  • Turek, F. W., Pinto, L., Vitaterna, M., Penev, P., Zee, P. C., & Takahashi, J. S. (1995). Pharmacological and genetic approaches for the study of circadian rhythms in mammals. Frontiers in Neuroendocrinology, 16, 191–223.

    PubMed  CAS  Google Scholar 

  • Valentinuzzi, V. S., Scarbrough, K, Takahashi, J. S., & Turek, E W. (1997). Effects of aging on the circadian rhythm of wheel-running activity in C57BL/6 mice. American, journal of Physiology, 273, R1957–121964.

    CAS  Google Scholar 

  • Van Cauter, E., & Plat, L. (1996). Physiology of growth hormone secretion during sleep. Journal of Pediatrics, 128, S32–S37.

    PubMed  Google Scholar 

  • Van der Woude, P. F., Goudsmith, E., Wierda, M., Purba, J. S., Hofman, M. A., Bogte, H., & Swaab, D. E (1995). No vasopressin cell loss in the human hypothalamus in aging and Alzheimer’s disease. Neurobiology of Aging, 16, 11–18.

    PubMed  Google Scholar 

  • Van Gool, W. A., & Mirmiran, M. (1986). Effects of aging and housing in an enriched environment upon sleep-wake patterns in rats. Sleep, 9, 335–347.

    PubMed  Google Scholar 

  • Van Gool, W. A., Witting, W., & Mirmiran, M. (1987). Age-related changes in circadian sleep-wakefulness rhythms in male rats isolated from time cues. Brain Research, 413, 384–387.

    PubMed  Google Scholar 

  • Van Luijtelaar, M. G. P. A., Tonnaer, J. A. D. M., & Steinbusch, H. W. M. (1989). Similarities between aberrant serotonergic fibers in the aged and 5,7-DHT denervated young adult rat brain. Experimental Brain Research, 78, 81–89.

    Google Scholar 

  • Van Reeth, O., Zhang, Y., Zee, P. C., & Turek, E W. (1992). Aging alters feedback effects of the activity-rest cycle on the circadian clock. American Journal of Physiology, 263, R981–R986.

    PubMed  Google Scholar 

  • Van Reeth, O., Zhang, Y., Reddy, A., Zee, P. C., & Turek, E W. (1993). Aging alters the entraining effects of an activity-inducing stimulus on the circadian clock. Brain Research, 607, 286–292.

    PubMed  Google Scholar 

  • Van Reeth, O., Sturis, J., Bryne, M. M., Blackman, J. D., L’Hermite-Balériaux, M., Leproult, R., Oliner, C., Refetoff, S., Turek, E W., & Van Canter, E. (1994). Nocturnal exercise phase-delays the circadian rhythms of melatonin and thyrotropin secretion in normal men. American Journal of Physiology, 266, E964–E974.

    PubMed  Google Scholar 

  • Viswanathan, N., & Davis, E C. (1995). Suprachiasmatic nucleus grafts restore circadian function in aged hamsters. Brain Research, 686, 10–16.

    PubMed  CAS  Google Scholar 

  • Vitaterna, M. H., King, D. P., Chang, A. M., Kornhauser, J. M., Lowrey, P. L., McDonald, J. D., Dove, W. E, Pinto, L. H., Turek, E W., & Takahashi, J. S. (1994). Mutagenesis and mapping of a mouse gene, clock, essential for circadian behavior. Science, 264, 719–725.

    PubMed  CAS  Google Scholar 

  • Vitaterna, M. H., Chang, A.M., King, D. P., Pinto, L. H., Turek, E W., & Takahashi, J. S. (1996). Heterozygosity at the clock locus alters phase response curves to light in mice. Society for Research on Biological Rhythms, Abstracts, 200, 127.

    Google Scholar 

  • Wehr, T. A. (1991). The durations of human melatonin secretion and sleep respond to changes in day length (photoperiod). Journal of Clinical Endocrinology and Metabolism, 73, 1276–1280.

    PubMed  CAS  Google Scholar 

  • Wehr, T. A., Moul, D. E., Barbato, G., Giesen, H. A., Seidel, J. A., Barker, C., 8e Bender, C. (1993). Conservation of photoperiod-responsive mechanisms in humans. American Journal of Physiology, 265, R846–R857.

    PubMed  CAS  Google Scholar 

  • Weiland, N. G., & Wise, P. M. (1990). Aging progressively decreases the densities and alters the diurnal rhythms of alpha-1 adrenergic receptors in selected hypothalamic regions. Endocrinology, 126, 2392–2397.

    PubMed  CAS  Google Scholar 

  • Welsh, D. K., Richardson, G. S., & Dement, W. C. (1986). Effect of age on the circadian pattern of sleep and wakefulness in the mouse. Journal of Gerontology, 41, 579–586.

    PubMed  CAS  Google Scholar 

  • Whealin, J. M., Burwell, R. D., & Gallagher, M. (1993). The effects of aging on diurnal water intake and melatonin binding in the suprachiasmatic nucleus. Neuroscience Letters, 154, 149–152.

    PubMed  CAS  Google Scholar 

  • Wise, P. M., Walovitch, R. C., Cohen, I. R., Weiland, N. G., & London, D. E. (1987). Diurnal rhythmicity and hypothalamic deficits in glucose utilization in aged ovariectomized rats. Journal of Neuroscience, 7, 3469–3473.

    PubMed  CAS  Google Scholar 

  • Wise, P. M., Cohen, I. R., Weiland, N. G., & London, D. E. (1988). Aging alters the circadian rhythm of glucose utilization in the suprachiasmatic nucleus. Proceedings of the National Academy of Sciences of the USA, 85, 5305–5309.

    PubMed  CAS  Google Scholar 

  • Wise, P. M., Scarbrough, K., Larson, G. H., Lloyd, J. M., Weiland, N. G., & Chiu, S. (1991). Neuroendocrine influences on aging of the female reproductive system. Frontiers in Neuroendocrinology, 12, 323–356.

    Google Scholar 

  • Witting, W., Mirmiran, M., Bos, N. P. A., & Swaab, D. F. (1993). Effect of light intensity on diurnal sleep-wake distribution in young and old rats. Brain Research Bulletin, 30, 157–162.

    Google Scholar 

  • Witting, W., Mirmiran, M., Bos, N. P. A., & Swaab, D. E (1994). The effect of old age on the free-running period of circadian rhythms in rat. Chronobiology International, 11, 103–112.

    PubMed  CAS  Google Scholar 

  • Zee, P. C., Rosenberg, R. S., & Turek, F. W. (1992). Effects of aging on entrainment and rate of resynchronization of the circadian locomotor activity. American Journal of Physiology, 263, 1099–1103.

    Google Scholar 

  • Zhang, Y. (1995). Photic and nonphotic manipulation of the circadian clock of young and aged golden hamsters. Ph.D. Dissertation, Northwestern University, Evanston, Illinois.

    Google Scholar 

  • Zhang, Y., Kornhauser, J. M., Zee, P. C., Mayo, K. E., Takahashi, J. S., & Turek, E W. (1996). Effects of aging on light-induced phase-shifting of circadian behavioral rhythms, fos expression, and CREB phosphorylation in the hamster suprachiasmatic nucleus. Neuroscience, 70, 951–961.

    PubMed  CAS  Google Scholar 

  • Zhdanova, I. V., & Wurtman, R. J. (1997). Efficacy of melatonin as a sleep-promoting agent. Journal of Biological Rhythms, 12, 644–650.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2001 Springer Science+Business Media New York

About this chapter

Cite this chapter

Turek, F.W., Scarbrough, K., Penev, P., Labyak, S., Valentinuzzi, v.S., Van Reeth, O. (2001). Aging of the Mammalian Circadian System. In: Takahashi, J.S., Turek, F.W., Moore, R.Y. (eds) Circadian Clocks. Handbook of Behavioral Neurobiology, vol 12. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-1201-1_11

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-1201-1_11

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5438-3

  • Online ISBN: 978-1-4615-1201-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics