The pineal aging and death program. I. Grafting of old pineals in young mice accelerates their aging

Experimental work initiated in 1985 progressively demonstrated the aging-de laying and/or life-prolonging effects of circadian, nocturnal administratio n of the pineal indoleamine melatonin in old rodents, and the even more pro nounced aging-delaying effects of young-to-old pineal grafting. Another mod el, in which young pinealectomized mice were transplanted with pineal gland s from older donors, showed a remarkable aging-accelerating effect produced in the younger mice by the "old" pineal. More work showed that, not only t he course of aging can be modified, but even reversed. Apparently, aging is an evolutionary and developmental program similar to growth, onset of pube rty and maintenance of fertility, and is amenable to be modified. The novel observation is reported here that implantation of pineal glands from very old donors into the thymus of normal, non-pinealectomized young hosts, acce lerates their aging and induces an earlier death. No effect on aging and lo ngevity can be seen when the young mice are transplanted with a pineal glan d from young donors. It thus seems that the grafted pineal gland from a ver y old donor delivers active "aging and death messages" that cannot be perma nently antagonized by the existing own "young" pineal gland in the host. Th is new observation also suggests that the "program of aging," even in a dis ease-free individual, may be different from the "program of death." In fact , a very old pineal gland seems to dominate on a young pineal and thus prod uce an earlier death at a time when the genetically determined neuroendocri ne program, of growth, fertility and aging in the engrafted old pineal has expired. The mechanism for the explication of these aging-promoting mechani sms in the "pineal network" is under investigation.