The Pineal Aging and Death Program. I. Grafting of Old Pineals in Young Mice Accelerates Their Aging

Abstract

Experimental work initiated in 1985 progressively demonstrated the aging-delaying and/or life-prolonging effects of circadian, nocturnal administration of the pineal indoleamine melatonin in old rodents, and the even more pronounced aging-delaying effects of young-to-old pineal grafting. Another model, in which young pinealectomized mice were transplanted with pineal glands from older donors, showed a remarkable aging-accelerating effect produced in the younger mice by the "old" pineal. More work showed that, not only the course of aging can be modified, but even reversed. Apparently, aging is an evolutionary and developmental program similar to growth, onset of puberty 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, accelerates their aging and induces an earlier death. No effect on aging and longevity can be seen when the young mice are transplanted with a pineal gland from young donors. It thus seems that the grafted pineal gland from a very old donor delivers active "aging and death messages" that cannot be permanently antagonized by the existing own "young" pineal gland in the host. This new observation also suggests that the "program of aging," even in a disease-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 produce an earlier death at a time when the genetically determined neuroendocrine program of growth, fertility and aging in the engrafted old pineal has expired. The mechanism for the explication of these aging-promoting mechanisms in the "pineal network" is under investigation.