Timekeeping in genetically programmed aging

Kloeden, Peter E.; Rössler, R.; Rössler, Otto E.

doi:10.1016/0531-5565(93)90001-t

Cited by 18 publications

(4 citation statements)

References 29 publications

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“…Melatonin signal is closely dependent on the amplitude of nocturnal melatonin secretion, which is probably genetically determined [52]. As suggested by several groups [53, 54], the decrease of melatonin amplitude and/or of the duration of its nocturnal peak could be responsible for an internal temporal desynchronization with a consequent poor adaptability to the internal and external environmental changes and thus to the deterioration of health. Therefore, it is interesting that in centenarian subjects, a highly selected group considered as a good expression of successful aging, the nocturnal excretion of aMT6s was significantly higher than diurnal levels; when expressed as percent of the total 24 hr amount the diurnal and nocturnal excretion rate were quite similar in centenarians and young subjects while no differences between the two urine samples were found in ‘normal’ aging, suggesting a certain maintenance of the circadian organization of melatonin secretion in the former but not in the latter.…”

Section: Discussionmentioning

confidence: 99%

Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians

Magri

Sarra

Cinchetti

et al. 2004

Journal of Pineal Research

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Melatonin secretion is an endogenous synchronizer, and it may possess some anti-aging properties. Thus we examined melatonin levels in physiological aging, in extreme senescence and in senile dementia. In healthy old (age 66-94 yr) and young subjects (age 23-39 yr) and in demented patients (age 68-91 yr) plasma melatonin was measured by radioimmunoassay in eight serial blood samples. In centenarians (age 100-107 yr) melatonin levels were estimated by assaying urinary 6-hydroxymelatonin sulfate (aMT6s) in two different urine samples collected from 08:00 to 20:00 hours and from 20:00 to 08:00 hours. These data were compared with the aMT6s excretion of old and young controls. Elderly subjects, demented or not, exhibited a flattened circadian profile of plasma melatonin, because of the suppression of the nocturnal peak. An age-related decline of the circadian amplitude of the melatonin rhythm occurred in old subjects, especially in demented individuals. Furthermore, the melatonin nocturnal peak was significantly correlated with the severity of the cognitive impairment. aMT6s urinary excretion also declined with age. However, as in young controls, in centenarians the aMT6s excretion was significantly higher at night than during the day. In conclusion, pineal melatonin secretion is affected by age and by the degree of cognitive impairment. In centenarians the maintenance of the circadian organization of melatonin secretion may suggest that the amplitude of the nocturnal peak and/or the persistence of a prevalent nocturnal secretion may be an important marker of biological age and of health status.

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Section: Discussionmentioning

confidence: 99%

Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians

Magri

Sarra

Cinchetti

et al. 2004

Journal of Pineal Research

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“…Since melatonin may be involved in several physiological [Piccoli et al, 1991;Reiter, 1992;Dawson et al, 1993;Kloeden et al, 1993;Dollins et al, 19941 and pathological processes [Piccoli et al, 1991;Bartsch et al, 1992;Sandyk, 1992a, it would be of great interest to detect the type of melatonin excretion using a simple noninvasive procedure such as the overnight urine melatonin measurement. In that way it would be possible to research melatonin's role, if any, in the development of several diseases in which low or high melatonin levels have been reported [Touitou et al, 1985;Wetterberg, 1985;Almay et al, 1987;Oosthuizen et al, 19891.…”

Section: Discussionmentioning

confidence: 99%

Low and high melatonin excretors among healthy individuals

Bergiannaki

Soldatos

Paparrigopoulos

et al. 1995

Journal of Pineal Research

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To meet the need of establishing firm normative data regarding the secretion/excretion of human melatonin, nighttime urinary melatonin of 16 healthy volunteers was measured in samples collected monthly over a period of 1 year. Low melatonin excretors (N = 8) were distinguished from high melatonin excretors (N = 8), based on a cut-off mean melatonin value of 0.25 nmol/l. There was no overlap in any of the monthly melatonin values between the two groups, while their annual rhythms of melatonin excretion were not different in shape. Since no obvious factors (age, sex, height, weight, etc.) were responsible for the observed differences, the distinction between low and high nocturnal excretion and by inference secretion of melatonin most likely reflects genetically determined variable levels of the noradrenergic secretory drive and/or variable N-acetyltransferase/hydroxyindole-O-methyltransferase enzymatic activity during the night.

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“…Cells seem to keep track of the number of divisions that they have completed. This has given rise to the idea of an "aging clock" timed by cell division (Kloeden, Rossler, & Rossler, 1993). Various counting devices have been proposed.…”

Section: Is There a Cell Clock That Times Aging?mentioning

confidence: 99%

“…Other hypotheses propose that an aging clock is determined more at the physiological level. It could be timed by the pineal gland or by genes controlling circadian rhythm (Kloeden et al, 1993;Sassone-Corsi, 1994). The mechanism by which a cell division counting clock would operate at the whole animal level is not fully understood.…”

Section: Is There a Cell Clock That Times Aging?mentioning

confidence: 99%

Genetic Control of the Aging Process: A Review and Interpretation

Enesco¹

1996

Can. J. Aging

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RÉSUMÉLe processus de vieillissement est sous contrôle génétique. Le point de vue traditionnel, dérivé de la biologie évolutive, est que le vieillissement est un trait polygénique, contrôlé par un grand nombre de gènes, chacun avec un effet additif. Un autre point de vue est développé ici, en ajoutant qu'il y a un nombre limité de gènes importants dans le contrôle du vieillissement. Ces derniers peuvent inclure les gènes protecteurs qui assurent l'exactitude de la synthèse de protéines et aussi les gènes qui servent à activer ou à retarder le processus de vieillissement. On continue à développer la technologie génétique afin de faire la carte complète du génome humain. Ces percées offrent la possibilité de comprendre les mécanismes génétiques du vieillissement et même d'envisager la thérapie génétique pour les maladies associées au vieillissement.

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Timekeeping in genetically programmed aging

Cited by 18 publications

References 29 publications

Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians

Qualitative and quantitative changes of melatonin levels in physiological and pathological aging and in centenarians

Low and high melatonin excretors among healthy individuals

Genetic Control of the Aging Process: A Review and Interpretation

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