Alterations in Nocturnal Serum Melatonin Levels In Humans With Growth and Aging*

Waldhauser, Franz; Weiszenbacher, Gunther; Tatzer, Ernst; Gisinger, B.; Waldhauser, M.; Schemper, M.; Frisch, H

doi:10.1210/jcem-66-3-648

Cited by 381 publications

(245 citation statements)

References 18 publications

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“…Secondly, there is no association between pineal size and age (Hasegawa et al 1987), which confirms the predominant, genetical determination of pineal size (Schmidt et al 1995;Bhatnagar 1990). Thirdly, there is a negative correlation between age and aMT6s (Sack et al 1986;Sharma et al 1989;Humbert and Pevet 1994;Zhdanova et al 1997;Waldhauser et al 1988;Myers and Badia 1995). Figure 1.…”

Section: Discussionmentioning

confidence: 89%

A New Concept for Melatonin Deficit On Pineal Calcification and Melatonin Excretion

Kunz

1999

Neuropsychopharmacology

138

102

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Even though exogenous melatonin has proven to influence sleep and circadian parameters, low endogenous melatonin is not related to sleep disturbances, nor does it predict response to melatonin replacement therapy. In this manuscript, we present a new concept towards a definition of a melatonin deficit. The purpose of the study was to introduce a marker for an intra-individual decrease in melatonin production. Therefore, we developed a method to quantify the degree of pineal calcification (DOC) usingIn mammals, the circadian timing system has proven to be involved in the daily variation of almost any physiological and psychological variable evaluated so far (Weitzman et al. 1978;Wirz-Justice 1987;Johnson et al. 1992;Dijk and Czeisler 1995;Boivin et al. 1997). The rhythm of the circadian pacemaker comprised in the nuclei suprachiasmatici (SCN) becomes entrained to the environmental 24-hour rhythm, predominantly by two zeitgebers, light and melatonin (Dawson and Armstrong 1996).Melatonin influences the circadian phase in humans inversely compared to light. In particular, this drug delays circadian rhythms when administered in the morning and advances them when administered in the afternoon or early evening according to a phase response curve (PRC), which is nearly opposite in phase to the PRC's for light exposure (Lewy et al. 1992). Melatonin has proven to exert a chronobiotic mode of action (Dawson and Armstrong 1996) by its ability to facilitate the post-flight adaptation to jet-lag (Arendt et al. 1986), to phase advance the sleep of patients suffering from a phase-delay syndrome (Dahlitz et al. 1991;Tzischinsky et al. 1993), and to re-entrain the sleep-wake cycle of patients with a non-24-hour rhythm, such as in the blind, to the environmental light-dark cycle (Arendt et al. 1988;Lapierre and Dumont 1995;McArthur et al. 1996).However, in only one of the clinical studies (Haimov et al. 1995), in which exogenous melatonin proved usefulness, did low endogenous melatonin excretion predict response (Garfinkel et al. 1995;Hughes et al. 1998 Lushington et al. 1998;Youngstedt et al. 1998). Furthermore, normative data as to the amount of melatonin secretion demonstrate a huge inter-individual variability in humans (Dawson et al. 1992;Bergiannaki et al. 1995;Smith et al. 1997). Thus, existing normative data on melatonin excretion in a "healthy population" might only be considered normal in the sense that they are representative for the normal scatter. But since there is yet no pathology that can be attributed to either high or low melatonin levels, "normative" in this context may not necessarily indicate being healthy. The question arises, does a melatonin deficit or a hypopinealism exist at all?In a previously reported pilot-study we showed that the degree of pineal calcification (DOC) correlated positively to the incidence of chronic daytime tiredness as well as the subjective perception of sleep disturbances (Kunz et al. 1998). The basic assumption in that study was the hypothesis that an increasing degree of pineal c...

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Section: Discussionmentioning

confidence: 89%

A New Concept for Melatonin Deficit On Pineal Calcification and Melatonin Excretion

Kunz

1999

Neuropsychopharmacology

138

102

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“…Thus, the difference observed in that 1997). An investigation of the relationship between melatonin study may be explained by the age-related decline in melatonin phase and sleep may provide a better clue as to the connection excretion (Sack et al 1986;Sharma et al 1989;Waldhauser et al between the melatonin and sleep systems. This is more likely 1988).…”

Section: Discussionmentioning

confidence: 99%

6‐Sulfatoxymelatonin excretion and self‐reported sleep in good sleeping controls and 55–80‐year‐old insomniacs

Lushington¹,

Lack

Kennaway³

et al. 1998

Journal of Sleep Research

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The pineal hormone melatonin is thought to play a role in sleep initiation and maintenance. This was examined in a large sample of good sleeping controls ( n=52) and sleep maintenance insomniacs (n=56), aged 55–80 y. Subjects collected 5 d of self‐reported sleep diary measures, and 12‐h urine samples (08.00–20.00 and 20.00–08.00 h) for analysis of the urinary melatonin metabolite, 6‐sulphatoxymelatonin (aMT.6S). Insomniacs reported a significantly greater amount of wake after sleep onset, less sleep in total, less efficient sleep and poorer quality sleep compared to controls. However, no significant differences in melatonin excretion were observed between controls and insomniacs, with both groups showing similar mean (SEM) 12‐h night‐time [30.9 (2.9) vs. 30.6 (3.3) nmoles, respectively] as well as 24‐h total [38.7 (3.4) vs. 36.7 (3.8)] aMT.6S excretion levels. No significant correlations were observed with any sleep parameters nor any effects of medication (anti‐inflammatory agents, hormone replacement therapy, and an undifferentiated group of medications). The present results do not support a simple relationship between total melatonin production and self‐reported sleep quality and duration in the aged.

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“…Aged male rhesus macaques, like aged men, show a significant decline in the amplitude of their 24-h melatonin (Figs. 1a, e;Iguchi et al 1982;Waldhauser et al 1988;Sharma et al 1989;Thomas and Miles 1989;Haimov et al 1994;Zeitzer et al 1999;Roth et al 2001;Downs et al 2004) and testosterone rhythms (Figs. 1b, f;Plymate et al, 1989;Feldman et al 2002;Luboshitzky et al 2003;Garyfallou et al 2005;Kaufman and Vermeulen 2005;Page et al 2007;Schlatt et al 2008;Bremner 2010), and an even more pronounced attenuation of their 24-h DHEAS rhythm (Figs.…”

Section: Age-related Endocrine Changesmentioning

confidence: 95%

Age-related changes in neuroendocrine rhythmic function in the rhesus macaque

Urbanski

Sorwell

2011

AGE

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Many environmental conditions show rhythmic changes across the 24-h day; these include changes in light intensity, ambient temperature, food availability, and presence or absence of predators. Consequently, many organisms have developed corresponding adaptations, which ensure that specific physiological and behavioral events occur at an appropriate time of the day. In mammals, the underlying mechanism responsible for synchronizing internal biochemical processes with circadian environmental cues has been well studied and is thought to comprise three major components: (1) photoreception by the retina and transmission of neural signals along the retinohypothalamic tract, (2) integration of photoperiodic information with an internal reference circadian pacemaker located in the suprachiasmatic nucleus, and (3) dissemination of circadian information to target organs, via the autonomic nervous system and through humoral pathways. Given the importance that neuroendocrine rhythms play in coordinating normal circadian physiology and behavior, it is plausible that their perturbation during aging contributes to the etiology of age-related pathologies. This mini-review highlights some of the most dramatic rhythmic neuroendocrine changes that occur in primates during aging, focusing primarily on data from the male rhesus macaques (Macaca mulatta). In addition to the ageassociated attenuation of hormone levels and reduction of humoral circadian signaling, there are also significant age-related changes in intracrine processing enzymes and hormone receptors which may further affect the functional efficacy of these hormones. Rhesus macaques, like humans, are large diurnal primates and show many of the same physiological and behavioral circadian changes during aging. Consequently, they represent an ideal translational animal model in which to study the causes and consequences of age-associated internal circadian disruption and in which to evaluate novel therapies.

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Alterations in Nocturnal Serum Melatonin Levels In Humans With Growth and Aging*

Cited by 381 publications

References 18 publications

A New Concept for Melatonin Deficit On Pineal Calcification and Melatonin Excretion

A New Concept for Melatonin Deficit On Pineal Calcification and Melatonin Excretion

6‐Sulfatoxymelatonin excretion and self‐reported sleep in good sleeping controls and 55–80‐year‐old insomniacs

Age-related changes in neuroendocrine rhythmic function in the rhesus macaque

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