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      The Pineal Control of Aging. : The Effects of Melatonin and Pineal Grafting on the Survival of Older Mice

      , , ,
      Annals of the New York Academy of Sciences
      Wiley-Blackwell

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          Putative melatonin receptors in a human biological clock.

          In vitro autoradiography with 125I-labeled melatonin was used to examine melatonin binding sites in human hypothalamus. Specific 125I-labeled melatonin binding was localized to the suprachiasmatic nuclei, the site of a putative biological clock, and was not apparent in other hypothalamic regions. Specific 125I-labeled melatonin binding was consistently found in the suprachiasmatic nuclei of hypothalami from adults and fetuses. Densitometric analysis of competition experiments with varying concentrations of melatonin showed monophasic competition curves, with comparable half-maximal inhibition values for the suprachiasmatic nuclei of adults (150 picomolar) and fetuses (110 picomolar). Micromolar concentrations of the melatonin agonist 6-chloromelatonin completely inhibited specific 125I-labeled melatonin binding, whereas the same concentrations of serotonin and norepinephrine caused only a partial reduction in specific binding. The results suggest that putative melatonin receptors are located in a human biological clock.
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            Brain aging correlates: retardation by hormonal-pharmacological treatments.

            Mid-aged rats were either adrenalectomized and chronically maintained, or left intact and treated daily for a 9- to 10-month period with a potent analog of the peptide adrenocorticotropin (residues 4 to 9), which has some stimulant properties, or with the neural stimulant pentylenetetrazole. All three treatments reduced hippocampal morphologic correlates of brain aging (neuronal loss, glial reactivity). The pentylenetetrazole and peptide treatments also improved reversal learning. These results suggest that certain endogenous peptides, with stimulant properties, may also exert long-term, trophic effects on brain structure and function.
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              Circadian rhythms of melatonin and cortisol in aging.

              The relationship of age to the circadian rhythms of melatonin and cortisol was investigated in 44 men and 27 women (age range 19-89 years). Subjects were physically and psychiatrically normal. Four hourly serial blood samples were drawn from 8:00 AM until 8:00 AM the next day, with additional samples at 10:00 PM and 2:00 AM. The indoor illumination was restricted to 300 lux during day and 50 lux during the night. Plasma melatonin and cortisol were estimated by radioimmunoassay. Results show that the means of melatonin and cortisol values decreased significantly with age when the subjects were divided into three age groups, i.e., 19-25 years, 42-65 years, and 66-89 years. They also showed a significant negative correlation with age. The acrophases of the two hormonal rhythms, however, showed different relationships to age. The acrophase of melatonin rhythm showed a positive correlation with age (r = 0.38, p less than 0.001), and cortisol showed a negative correlation with age (r = -0.56, p greater than 0.001). It is suggested that this may indicate a weakened responsiveness of the circadian system in the elderly to the day-night cycle and an altered relationship between the pacemakers driving melatonin and cortisol circadian rhythms. This may thus represent a biomarker for the intrinsic process of the aging of the brain.
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                Author and article information

                Journal
                Annals of the New York Academy of Sciences
                Ann NY Acad Sci
                Wiley-Blackwell
                0077-8923
                1749-6632
                July 1991
                July 1991
                : 621
                : 1 Physiological
                : 291-313
                Article
                10.1111/j.1749-6632.1991.tb16987.x
                48ce7fc0-df02-4c87-ae19-9e568dd40e60
                © 1991

                http://doi.wiley.com/10.1002/tdm_license_1.1

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