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Do plasma melatonin concentrations decline with age?
Abstract
Purpose Numerous reports that secretion of the putative sleep-promoting hormone melatonin declines with age have led to suggestions that melatonin replacement therapy be used to treat sleep problems in older patients. We sought to reassess whether the endogenous circadian rhythm of plasma melatonin concentration changes with age in healthy drug-free adults.Methods We analyzed the amplitude of plasma melatonin profiles during a constant routine in 34 healthy drug-free older subjects (20 women and 14 men, aged 65 to 81 years) and compared them with 98 healthy drug-free young men (aged 18 to 30 years).Results We could detect no significant difference between a healthy and drug-free group of older men and women as compared to one of young men in the endogenous circadian amplitude of the plasma melatonin rhythm, as described by mean 24-hour average melatonin concentration (70 pmol/liter vs 73 pmol/liter, P = 0.97), or the duration (9.3 hours vs 9.1 hours, P = 0.43), mean (162 pmol/liter vs 161 pmol/liter, P = 0.63), or integrated area (85,800 pmol x min/liter vs 86,700 pmol x min/liter, P = 0.66) of the nocturnal peak of plasma melatonin.Conclusion These results do not support the hypothesis that reduction of plasma melatonin concentration is a general characteristic of healthy aging. Should melatonin replacement therapy or melatonin supplementation prove to be clinically useful, we recommend that an assessment of endogenous melatonin be carried out before such treatment is used in older patients.
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“Several studies have reported declines in melatonin levels with ageing, although others find no difference compared with younger people in a healthy population237,238.”
From Rhythms of life: circadian disruption and brain disorders across the lifespan (2019) · cites this paper as [238]
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Cites
Bright Light Induction of Strong (Type 0) Resetting of the Human Circadian Pacemaker
Czeisler, C. A., Kronauer, R. E., Allan, J. S., Duffy, J. F., Jewett, M. E., Brown, E. N., & Ronda, J. M. (1989) · Science · doi:10.1126/science.2734611 · Cited by 946
Self-citationExposure to Bright Light and Darkness to Treat Physiologic Maladaptation to Night Work
Czeisler, C. A., Johnson, M. P., Duffy, J. F., Brown, E. N., Ronda, J. M., & Kronauer, R. E. (1990) · New England Journal of Medicine · doi:10.1056/nejm199005033221801 · Cited by 580
Self-citationHuman Melatonin Production Decreases With Age
Sack, R. L., Lewy, A. J., Erb, D. L., Vollmer, W. M., & Singer, C. M. (1986) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1986.tb00760.x · Cited by 415
Alterations in Nocturnal Serum Melatonin Levels In Humans With Growth and Aging*
Waldhauser, F., Weiszenbacher, G., Tatzer, E., Gisinger, B., Waldhauser, M., SCHEMPER, M., & Frisch, H. (1988) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-66-3-648 · Cited by 407
Human Melatonin Suppression by Light is Intensity Dependent
Mclntyre, I. M., Norman, T. R., Burrows, G. D., & Armstrong, S. M. (1989) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1989.tb00412.x · Cited by 389
Age-Dependent Reduction in Serum Melatonin Concentrations in Healthy Human Subjects
Iguchi, H., Kato, K., & Ibayashi, H. (1982) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-55-1-27 · Cited by 381
Neuroendocrine rhythms and sleep in aging men
van Coevorden, A., Mockel, J., Laurent, E., Kerkhofs, M., L'Hermite-Baleriaux, M., Decoster, C., Neve, P., & Van Cauter, E. (1991) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1991.260.4.e651 · Cited by 336
Sleep disorders and melatonin rhythms in elderly people
Haimov, I., Laudon, M., Zisapel, N., Souroujon, M. C., Nof, D., Shlitner, A., Herer, P., Tzischinsky, O., & Lavie, P. (1994) · BMJ · doi:10.1136/bmj.309.6948.167 · Cited by 315
Relationship between Melatonin Rhythms and Visual Loss in the Blind
Lockley, S. W., Skene, D. J., Arendt, J., Tabandeh, H., Bird, A. C., & Defrance, R. (1997) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.82.11.4355 · Cited by 312
Claustrat, B., Chazot, G., Brun, J., Jordan, D., & Sassolas, G. (1984) · PubMed · Cited by 293
The pineal gland and melatonin in relation to aging: A summary of the theories and of the data
Reiter, R. J. (1995) · Experimental Gerontology · doi:10.1016/0531-5565(94)00045-5 · Cited by 286
Adaptation to abrupt time shifts of the oscillator(s) controlling human circadian rhythms.
Mills, J. N., Minors, D. S., & Waterhouse, J. M. (1978) · The Journal of Physiology · doi:10.1113/jphysiol.1978.sp012582 · Cited by 285
Circadian rhythms of melatonin and cortisol in aging
Sharma, M., Palacios-Bois, J., Schwartz, G., Iskandar, H., Thakur, M., Quirion, R., & Nair, N. P. V. (1989) · Biological Psychiatry · doi:10.1016/0006-3223(89)90178-9 · Cited by 260
Hughes, R. J., Sack, R. L., & Lewy, A. J. (1998) · SLEEP · doi:10.1093/sleep/21.1.52 · Cited by 202
Posture influences melatonin concentrations in plasma and saliva in humans
Deacon, S., & Arendt, J. (1994) · Neuroscience Letters · doi:10.1016/0304-3940(94)91059-6 · Cited by 185
Touitou, Y., Fèvre, M., Lagoguey, M., Carayon, A., Bogdan, A., Reinberg, A., Beck, H., Cesselin, F., & Touitou, C. (1981) · Journal of Endocrinology · doi:10.1677/joe.0.0910467 · Cited by 175
Nonsteroidal anti-inflammatory drugs alter body temperature and suppress melatonin in humans
Murphy, P., Myers, B. L., & Badia, P. (1996) · Physiology & Behavior · doi:10.1016/0031-9384(95)02036-5 · Cited by 137
Plasma melatonin—An index of brain aging in humans?
Nair, N. P. V., Hariharasubramanian, N., Pilapil, C., Isaac, I., & Thavundayil, J. (1986) · Biological Psychiatry · doi:10.1016/0006-3223(86)90141-1 · Cited by 135
Circadian rhythm of plasma melatonin in endogenous depression
Nair, N. P. V., Hariharasubramanian, N., & Pilapil, C. (1984) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/0278-5846(84)90044-7 · Cited by 133
Bojkowski, C., & Arendt, J. (1990) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1990.tb03882.x · Cited by 127
Touitou, Y., Fèvre, M., Bogdan, A., Reinberg, A., Prins, J. D., Beck, H., & Touitou, C. (1984) · European Journal of Endocrinology · doi:10.1530/acta.0.1060145 · Cited by 125
REDUCED NOCTURNAL MELATONIN SECRETION IN CHRONIC SCHIZOPHRENIA: RELATIONSHIP TO BODY WEIGHT
FERRIER, I. N., ARENDT, J., JOHNSTONE, E. C., & CROW, T. J. (1982) · Clinical Endocrinology · doi:10.1111/j.1365-2265.1982.tb01577.x · Cited by 118
Changes in Endocrine Orcadian Rhythms as Markers of Physiological and Pathological Brain Aging
Magri, F., Locatelli, M., Balza, G., Molla, G., Cuzzoni, G., Fioravanti, M., Solerte, S. B., & Ferrari, E. (1997) · Chronobiology International · doi:10.3109/07420529709001459 · Cited by 111
Melatonin in human cerebrospinal fluid in daytime; Its origin and variation with age
Brown, G. M., Young, S. N., Gauthier, S. G., Tsui, H. W., & Grota, L. J. (1979) · Life Sciences · doi:10.1016/0024-3205(79)90498-3 · Cited by 97
Role of Melatonin and Pineal Peptides in Neuroimmunomodulation
FRASCHINI, F., & Reiter, R. J. (1991) · Springer eBooks · doi:10.1007/978-1-4615-3756-4 · Cited by 95
The Pineal Gland: A Review of the Physiologic Literature.
(1955) · Annals of Internal Medicine · doi:10.7326/0003-4819-42-4-960_1 · Cited by 94
Neuroendocrine Correlates of the Aging Brain in Humans
Ferrari, E., Magri, F., Dori, D., Migliorati, G., Nescis, T., Molla, G., Fioravanti, M., & Solerte, S. B. (2008) · Neuroendocrinology · doi:10.1159/000126869 · Cited by 90
Touitou, Y., Fèvre‐Montange, M., Proust, J., Klinger, E., & Nakache, J. (1985) · European Journal of Endocrinology · doi:10.1530/acta.0.1080135 · Cited by 65
Williamson, B. L., Tomlinson, A. J., Mishra, P. K., Gleich, G. J., & Naylor, S. (1998) · Chemical Research in Toxicology · doi:10.1021/tx970202h · Cited by 65
Chrono-neuroendocrinological aspects of physiological aging and senile dementia.
Dori, D., Casale, G., Solerte, S. B., Fioravanti, M., Migliorati, G., Cuzzoni, G., & Ferrari, E. (1994) · PubMed · Cited by 59
Young, I. M., Francis, P. L., Leone, A. M., Stovell, P., & Silman, R. E. (1988) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1988.tb00770.x · Cited by 58
Age, alcoholism and depression are associated with low levels of urinary melatonin.
Wetterberg, L., Apéria, B., Gorelick, D. A., Gwirtzman, H. E., McGuire, M. T., Serafetinides, E. A., & Yuwiler, A. (1992) · PubMed Central · Cited by 57
Cagnacci, A., Soldani, R., & YEN, S. S. C. (1995) · Journal of Applied Physiology · doi:10.1152/jappl.1995.78.1.314 · Cited by 54
Guidelines for prescribing melatonin
Avery, D., Lenz, M., & Landis, C. A. (1998) · Annals of Medicine · doi:10.3109/07853899808999394 · Cited by 51
Kripke, D. F., Elliott, J. A., Youngstedt, S. D., & Smith, J. S. (1998) · Annals of Medicine · doi:10.3109/07853899808999388 · Cited by 46
Melatonin and the pineal gland
(1992) · European Journal of Cancer · doi:10.1016/0959-8049(92)90409-u · Cited by 40
Melatonin in Human Serum: Progress in Screening Investigation and Clinic
Birau, N. (1981) · Elsevier eBooks · doi:10.1016/b978-0-08-026400-4.50042-6 · Cited by 37
Thomas, D. R., & Miles, A. (1989) · Biological Psychiatry · doi:10.1016/0006-3223(89)90187-x · Cited by 34
Some Aspects of the Orcadian Time Structure in the Elderly
Touitou, Y. (2009) · Gerontology · doi:10.1159/000212573 · Cited by 33
Does a Centralized Clock for Ageing Exist?
Kloeden, P. E., Rössler, R., & Rössler, O. E. (2009) · Gerontology · doi:10.1159/000213216 · Cited by 32
Chrono-neuroendocrine markers of the aging brain
Ferrari, E., Magri, F., Locatelli, M., Balza, G., Nescis, T., Battegazzore, C., Cuzzoni, G., Fioravanti, M., & Solerte, S. B. (1996) · Aging Clinical and Experimental Research · doi:10.1007/bf03339588 · Cited by 31
Ohashi, Y., Okamoto, N., Uchida, K., Iyo, M., Mori, N., & Morita, Y. (1997) · Neurosignals · doi:10.1159/000109141 · Cited by 28
Grinevich, Y. A., & Labunetz, I. F. (1986) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1986.tb00749.x · Cited by 21
Timekeeping in genetically programmed aging
Kloeden, P. E., Rössler, R., & Rössler, O. E. (1993) · Experimental Gerontology · doi:10.1016/0531-5565(93)90001-t · Cited by 20
Circadian secretion of melatonin and thyrotropin in hospitalized aged patients
Murialdo, G., Costelli, P., Fonzi, S., Parodi, C., Torre, F., Cenacchi, T., & Pollen, A. (1993) · Aging Clinical and Experimental Research · doi:10.1007/bf03324125 · Cited by 19
Circadian rhythm of plasma melatonin and cortisol in endogenous depression
Nair, N. P. V., Hariharasubramanian, N., & Pilapil, C. (1984) · Journal of Steroid Biochemistry · doi:10.1016/0022-4731(84)90606-x · Cited by 10
Seasonal changes in the levels of antidiuretic hormone and melatonin in the elderly
Asplund, R., Åberg, H. E., & Wetterberg, L. (1995) · Journal of Pineal Research · doi:10.1111/j.1600-079x.1995.tb00154.x · Cited by 8
Commentary on the Articles by Arendt, Weaver, Mahle et al., and Guardiola-Lemaître
Borbély, A. A. (1997) · Journal of Biological Rhythms · doi:10.1177/074873049701200628 · Cited by 3
Attenuation of the circadian rhythms of core body temperature and melatonin with aging in women
Cagnacci, A. (1992) · IRIS UNIMORE (University of Modena and Reggio Emilia) · Cited by 2
Urinary 6-Sulphatoxymelatonin Excretion in Breast Cancer Patients and Control Subjects
Skene, D. J., Bojkowski, C., & Arendt, J. (1991) · Springer eBooks · doi:10.1007/978-1-4615-3756-4_34 · Cited by 1
Research works printed but not linked: 7
- Carnazzo, 1991, Variations of melatonin incretion in elderly patients affected by cerebral deterioration, Arch Gerontol Geriatr, S2, 123
- Claustrat, 1984, A chronobiological study of melatonin and cortisol secretion in depressed subjects, Biol Psychiatry, 19, 1215
- Klerman, 1996, Differential changes in amplitude with aging in blind persons, Soc Res Biol Rhythms, 5, 131
- Touitou, 1984, Patterns of plasma melatonin with ageing and mental condition, Acta Endocrinol, 106, 145
- Pang, 1984, Age and plasma levels of melatonin and N-acetylserotonin in human beings, Neurosci Lett, 16, S25
- Hughes, 1998, The role of melatonin and circadian phase in age-related sleep-maintenance insomnia, Sleep, 21, 52
- Haimov, 1994, The relationship between urinary 6-sulphatoxymelatonin rhythm and insomnia in old age, Adv Pineal Res, 8, 433
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Self-citationRotating night shifts and risk of breast cancer in women participating in the nurses׳ health study
Schernhammer, E. S., Laden, F., Speizer, F. E., Willett, W. C., Hunter, D. J., Kawachi, I., & Colditz, G. A. (2001) · JNCI Journal of the National Cancer Institute · doi:10.1093/jnci/93.20.1563 · Cited by 1,142
Regulation of adolescent sleep: Implications for behavior
CARSKADON, M. A., ACEBO, C., & JENNI, O. G. (2004) · Annals of the New York Academy of Sciences · doi:10.1196/annals.1308.032 · Cited by 792
Melatonin: Buffering the Immune System
Carrillo‐Vico, A., Lardone, P. J., Álvarez‐Sánchez, N., Rodríguez-Rodríguez, A., & Guerrero, J. M. (2013) · International Journal of Molecular Sciences · doi:10.3390/ijms14048638 · Cited by 763
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Metadata
- Authors
- Zeitzer, J. M., Daniels, J. E., Duffy, J. F., Klerman, E. B., Shanahan, T. L., Dijk, D.-J., & Czeisler, C. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Czeisler, Charles A
- Venue
- The American Journal of Medicine
- Publisher
- Elsevier BV
- Published
- 1999-11
- Volume
- 107
- Issue
- 5
- Pages
- 432-436
- ISSN
- 0002-9343 (ISSN-L)
- OpenAlex
- W2086521040
- Cited by
- 239
- References
- 55
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 8 · 2021: 5 · 2020: 12 · 2019: 3 · 2018: 3 · 2017: 5 · 2016: 6 · 2015: 5 · 2014: 2 · 2013: 12 · 2012: 3
- FWCI
- 6.06
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The American Journal of Medicine (publishedVersion)
- PubMed (publishedVersion)
- Open Research (University of Surrey) (submittedVersion)
- Surrey Research Insight Open Access (The University of Surrey) (submittedVersion)
- Funders
- National Institute on Aging (R01AG006072, R01-AG-06072, P01AG009975, P01 AG-09975)
- National Institute of Mental Health (R01 MH45130, R01MH045130)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Keywords
- plasma melatonin, aging, circadian rhythm, melatonin secretion, melatonin supplementation, healthy older adults
- MeSH terms
- Adult, Aged, Aged, 80 and over, Aging, Circadian Rhythm, Female, Humans, Male, Melatonin, Sleep Wake Disorders
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