J Pineal Res zyxwvutsrqponml 1994:16:17X-183 Printed zyxwvutsrqponm in the United States of America--all rights reserved zyxwvutsrqp Copyright zyxw 0 Munksgaard, zyxw I994 zy Journal of Pineal Research ISSN 0742-3098 zyx Calcium, calcification, and melatonin biosynthesis in the human pineal gland: zy A postmortem study into age-related factors Schmid HA, Requintina PJ, Oxenkrug GF, Sturner W. Calcium, calcification, and melatonin biosynthesis in the human pineal gland: A postmortem study into age-related factors. J. Pineal Res. 1994: 16:178- 183. Abstract: It is believed that pineal calcification may be age-associated and that the well-demonstrated age-related decline in melatonin biosynthesis may be an expression of an alteration in calcium homeostasis in the pinealocyte. Prior correlations of melatonin to calcium deposition and age were made on the basis of radiological or semiquantitative analysis. In this postmortem study of 33 subjects (age range 3 months to 65 years) calcium deposits measured by atomic absorption spectrometry correlated positively with age in day and night samples (day: r zyxwvutsrq = 0.56, P < 0.05; night: r = 0.818, P < 0.001). Nighttime (2200 h to 0800 h) pineal melatonin content (HPLC fluorometry) was higher than daytime melatonin levels (nighttime 3.80 * 0.3 vs. daytime 0.85 2 0.4 ng/mg protein). Nighttime calcium levels in the supernatant correlated negatively with melatonin content (r = -0.59, P < 0.05). Introduction In recent years, based on the well-known age- related decrease of melatonin, it has been hypoth- esized that aging is a consequence of pineal failure [Rozenchwaig et al., 19871 and that melatonin is an anti-aging hormone [Maestroni et al., 19881. In 1990 Kloeden proposed that “a centralized clock controlling aging is located in the pineal gland with the calcification process occurring there providing a highly accurate bio-inorganic timing mechanism.” However the tacit assumption that the degree of pineal calcium deposition is related to the ability of the pineal gland to produce melatonin [Reiter, 19921 has not been supported by histological evi- dence [Tapp and Huxley, 19721 or enzymatic stud- ies [Wurtman et al., 19641. Interestingly, it is not in primates but in rodents, best studied in the Mongo- lian gerbil, that increased pineal calcification and decreased melatonin production converge in old age [Reiter, 19921. To assume a causal relation is, however, currently unfounded. In humans, beginning at middle age, melatonin Hermann A. Schmid,’.2 Pura J. Requintina,’ Gregory F. Oxenkr~g,~.~ and William Sturner“ ‘Pineal Research Laboratory, VA Medical Center, Providence, RI; ‘Assistant Professor of Psychiatry and Human Behavior, Brown University; 3Professor of Psychiatry and Human Behavior, Brown University; 4State of Rhode Island, Professor of Pathology, Brown University, Providence, RI. Key words: calcium-calcium deposits-aging- melatonin Address reprint requests to Hermann Schmid, MD, PhD, Veterans Administration Medical Center, 830 Chalkstone Avenue, Providence, Rhode Island 02908. Received May 20, 1993; accepted February 14, 1994. biosynthesis (which is activated at night) decreases in general and in particular in regard to nocturnal peak and duration of nocturnal elevation [Iguchi et al., 1982; Nair et al., 1986; Sack et al., 1986; Waldhauser et al., 1988; Young et al., 19901. For the human pineal gland it was Kitay and Altschule [ 19541, later supported by Wildi and Frauchiger [ 19651, who first suggested that pineal calcifications increase with age. Arieti [ 19541 con- tested Kitay’s hypothesis by showing large individ- ual variations with sometimes little calcification in old age and massive accumulation in the first decade of life and was supported by the detection of large deposits already in the first year of life [Heidel, 1965; Scharenberg and Liss, 19651. In all human studies to date [Pelham et al., 1973; Commentz et al., 1986; Bojkowski and Arendt, 19901, correlations between melatonin and pineal calcification had been established solely on the basis of radiological and semi-quantitative measure- ments. These studies suggested the absence of a causal relationship. We decided, therefore, to un- 178