(Ed.- Dr. Pierpaoli would like readers to know that this article has been assembled for people who can appreciate its simplicity, and not for those "experts" whose minds allow no penetration of the simple and smart laws of Nature).
My mother-in-law; Emmy Hugly, living near Lucerne in Switzerland, is now 94 years-old, perfectly healthy and Parkinson-free in the last 15 years, with no intention to give up! Her story is narrated briefly in the book; Melatonin Miracle (1) and also in my recent book published in Italy; "An average of 120-years and beyond" (2). She goes shopping every day, and when we celebrate her birthdays, she loves dancing and playing the piano. I visit her from time to time, and make a record of her health and behavior with a video-camera. She loves to welcome visitors and journalists in her home, and they are all enthusiastically received! She prepares for them excellent tea and serves it with no shaking hands, but that wasn't the case 20 years ago, when she had severe and rapidly worsening Parkinson's disease.
Emmy is undoubtedly the longest melatonin-taking person in the world. She started in her early 80th year, in the last century, after I told her of my experiments with aging mice and how the administration of nocturnal melatonin in the drinking water was producing a remarkable rejuvenation, resulting in a delayed aging and consequent life prolongation. She asked me to give her the "pills" and she religiously followed my prescription. Some twenty years ago I prepared for her in my lab, 3mg melatonin capsules. Of course, she is now taking TI-MElatonin ® with zinc and selenium, as a kind an "evening rhythms" every night.
I believe that the embittered adversaries of "innocent" melatonin should visit her before their own life program has expired!
Of course, the lesson we can learn from Emmy is what I keep repeating in my; "shout in the desert" at various conferences (3-5): the reversal of aging we can observe in 2-3-year living mice, but in order to see what happens in humans we just must wait! Luckily for her, Emmy did not want to wait for a permit of the "Regulatory Bodies" in Switzerland to start taking melatonin; she wanted to live longer and Parkinson-free! According to the basic principles described by the great American anthropologist; Ashley Montagu in his famous book, Growing Young (6), Emmy is the living emblematic example of a neotenic (maintaining youth) person, born young and staying young until death, opposite to the typical necrophilic personality of the depressed and negative person, those who are born old and permanently old and aging until the "liberation" of death.
Now many people follow Emmy's virtuous path, regaining their vitality every day, month and year.
Aging is simply a neuroendocrine program in the brain!
In fact, the maintenance of hypothalamic-pituitary-pineal directed hormonal cyclicity, (day-night, lunar, seasonal) and its constant synchronization with the variability of planetary laws is the essential basis of health and life.
Every instant of our daily life is completely imprinted by solar and lunar cyclicity, from fertilization of the egg until the last breath of life. Life on our planet is shaped and inextricably associated with planetary and solar cyclicity, it is no wonder that its progressive deterioration, which is clearly represented by our growth, maturity, fertility and finally aging and death, is governed by extremely strong and genetically determined rules.
This aspect is amply represented by the demonstration that the hormones which regulate fertility and reproduction, are the same also controlling immunity (see Figure 1). But the dominance of the system gives priority to fertility and reproduction, in so far as Nature has thus allowed a species to survive (7). Apparently, the logic inevitability of this fact encounters the illogic opposition of many doctors and scientists! It is a riddle to me, not my demonstration of a central life and death clock in the pineal, but the absence of any experiment from those who criticize my work! It is a fact, that any kind of criticism bears no fundament unless it is founded on the repetition of a "doubtful" scientific work with the identical methods, and on its publication in a reviewed journal. Did anybody replicate my experiments with melatonin and pineal grafting before they criticized me? (8, 9) No! This is a true mystery of the 20th century. This question must be addressed in-particular, to those scientists who, without any justification whatsoever, spread injury and false news by hiding behind the safety curtain of "prestigious journals." (10, 11) Their behavior must be condemned and made public, because their irresponsible and irrational attacks have produced an awful lot of damage to millions of persons around the world.
Why Does Melatonin Prolong Life?
Melatonin prevents aging-related diseases, delays aging, and automatically prolongs life by simply impeding and postponing the progressive central, hypothalamic alteration of feedback hormonal regulation, as described beautifully by Professor Vladimir Dilman (12 ).
It does so not directly, but rather smartly, by maintaining youthful pineal function. In fact, obviously night administration of melatonin prevents the aging pineal gland from producing it. This regular night order "does not only work" on the pineal to only protect the "central hormonal director," but also induces a recovery of its regulatory capacity to modulate hormonal cyclicity, to the extent that the pineal gland recovers its juvenility. This is most significantly demonstrated by my experiments, in which a young pineal gland grafted into a much older recipient induces a very significant life prolongation.
Being as the grafted pineal is unable to produce by itself melatonin, obviously it is the pineal itself that is the central "life-clock." The aging pineal loses its ability to produce a night peak of melatonin, thus being a clear signal of its own aging. Therefore, we have now shown beyond any doubt that melatonin simply maintains the capacity of the young pineal to control cyclic release of all hormones, and it does this by maintaining and preventing pineal aging. (8, 9, 13) Not only is the pineal our central "life clock," it also actively induces our aging in the course of its life, aging and death "program." (14) Clearly genetically and evolutionary originated mechanisms in the pineal gland modulate the course of our life, and also generate the signals at the end of our life program.
This is shown in the experiments we reported in a recent work. (15) Therefore, the basic mechanisms for our aging must be sought in our pineal gland and in its links to the entire neuroendocrine network. (16) We age because our "pineal network" is "programmed" to deteriorate (12) and therefore we must use exogenous night melatonin in order to maintain its integrity, and thus prevent the typical course of the aging syndrome inside the pineal gland. Only natural melatonin can protect the pineal gland from programmed aging!
Pineal protection with melatonin means prevention of all diseases, including cancer!
As extravagant as it may appear, the re-synchronization of pineal-directed central neuroendocrine, (hormonal) cyclicity and its maintenance with nocturnal melatonin starting early in life, will inevitably maintain youthful conditions and avoid emergence of all kind of diseases. Even under the stressful conditions of modern life and the impact of a huge number of environmental "aggressors" on our body's integrity, melatonin will protect our "surveillance system," namely the vast array of cells and factors in the body which constantly survey and adapt our body to the needs of the situation. The immune system is under total control of hormones, (17) and the hormones are under the total control of the "pineal network!" How is it possible to conceive the emergence of diseases under a condition of perfect immunological balance? This does not mean at all that we can cure all diseases with melatonin, but we can help prevent them, and if unfortunately they have appeared, we can set up a very powerful emergency resistance system based on a series of immunopotentiating agents apt at "resetting the central clock," and hence make it suitable to delay and even arrest the course of the disease, be it a neurodegenerative disease, (such as Parkinson, multiple sclerosis etc.), a cardiovascular diseases or even cancer. This holistic concept of medicine has now found its biological evidence!
An obvious model: menopause
When we conducted in Rome, with Giulio Bellipanni at the Menopause Center of the "Madonna della Grazie" Clinic, the first clinical trial with 140 women, aged from 42 until 62, it showed that melatonin can reverse aging of the reproductive tract of women, abrogate all neurovegetative symptoms, regenerate thyroid functions, bring back hypophiseal gonadotropins to more juvenile levels, and even restore cyclicity in perimenopausal women. (18) We were happy to announce the news to all women. To our great astonishment and dismay, four different Journals, (Menopause, European Journal of Obstetrics and Gynecology, The New England Journal of Medicine and Steritity and Fertility), refused to publish our results! Their reasons were vague and disparate and one Journal kept us waiting for a whole year, asking for many changes and additions and finally telling us: "we don't have enough space!" I was naive: how could we expect that they would publish a paper showing that melatonin can simply replace and make obsolete hormones, by maintaining a perfect hormonal cyclicity?
Now I know, as a doctor taking care of many women with all kind of cyclicity problems, that melatonin is not a hormone itself, but truly a "queen of all hormones," which monitors and directs the whole "hormonal orchestra." This story shows that the enemies of melatonin are everywhere and that a true discovery meets with fierce opposition, but I wonder for how long will this last?
My view of melatonin and its intrinsic nature
After consideration and long meditation on the possible mechanisms of melatonin and its role in nature, I matured the conviction that melatonin possesses many levels of activities, which have been acquired in the course of evolution. As the great scientist Sir Peter Medawar used to say: "It is not molecules which evolved, but simply the use to which they are put." This means to me that melatonin, together with other molecules I am now identifying or have already found, certainly possesses some effects of minor value, such as an antioxidant, or via receptor-mediated activity in the brain, but as melatonin is a very ancient molecule in the evolution of life on our planet, its true nature is totally unknown and goes beyond our knowledge. It goes back to the origin of life and how light and darkness created the "life clock."
Melatonin, thanks to its cyclical structure, to the presence of an acetyl and methyl group, must possess a mysterious bioenergetic potential, which we are totally unable to perceive and understand. It is really a clue to the Creation!
Therefore, it is no wonder that its role and effects cannot be dissected by a number of "specialists," but only unified by a global biologist. Perhaps the next Stromboli Conference on Aging and Cancer (Ed.- June 5-11, 2004), is a suitable place to unveil this new dimension of life and death, in order that we can better adapt to the destiny of mortal mammals. After all, achieving very old age without disease is our ultimate goal.
The ultimate defiance and my bet on the future
What is going to happen? I bet that only a limited number of persons will be aware of the simple "melatonin message," because the complication of nature and not its logical interpretation is the current fashion. The gap between those who understand, and the stubborn opponents widens every day, let us wait and see. We are far ahead, "beyond melatonin" in so far as melatonin has succeeded in lighting our brain, enabling us to escape the traps of "modern medicine." At the same time, the use of melatonin to protect our pineal and prolonging us for a disease-free life, allows us more time to understand, and apply, to severely ill persons, the blessing of our New Innovative Medicine, by also making use of those molecules emerging from the brain "swamp" which, like melatonin, still keep the healing power conferred to them by nature in the course of evolution billions of years ago.
They are not drugs, they are life itself! But that is another story for another day.
W. Pierpaoli & W. Regelson, with Carol Colman: Melatonin Miracle. Nature's Age-Reversing, Disease-Fighting, Sex-Enhancing Hormone." Simon & Schuster, New York, 1995 (translated into 17 languages).
W. Pierpaoli & Pippo Zappulla: 120 and Longer, Average. Vivere Bene, Invecchiare Giovani e Morire Sani. Chrono-Med, Collana Arcadia, Brescia, Italy, 2003.
W. Pierpaoli & N.H. Spector, Editors: Neuroimmunomodulation: Interventions in Aging and Cancer. First Stromboli Conference on Aging and Cancer. Ann. N.Y. Academy Sci., 521, 1988.
W. Pierpaoli & N. Fabris, Editors: Physiological Senescence and its Postponement: Theoretical Approaches and Rational Interventions. Second Stromboli Conference on Aging and Cancer. Ann. N.Y. Acad. Sci., 621, 1991.
W. Pierpaoli, W. Regelson & N. Fabris, Editors. The Aging Clock. Third Stromboli Conference on Aging and Cancer. Ann. N.Y. Acad. Sci. 719, 1994.
A. Montagu: Growing Young. McGraw-Hill Book Company, New York, 1983.
W. Pierpaoli: Integrated Phylogenetic and Ontogenetic Evolution of Neuroendocrine and Identity-Defense, Immune Functions. In: Psychoneuroimmunology (R. Ader, Editor), Academic Press, New York, pp. 575-606, 1981.
W. Pierpaoli, A. Dall'Ara, E. Pedrinis & W. Regelson: The Pineal Control of Aging. The Effects of Melatonin and Pineal Grafting on the Survival of Older Mice.Ann. N.Y. Acad. Sci. 621, 291, 1991.
W. Pierpaoli & W. Regelson: Pineal Control of Aging: Effect of Melatonin and Pineal Grafting on Aging Mice. Proc. Natl. Acad. Sci. USA, 91, 787, 1994.
F.W. Turek: Melatonin Hype Hard to Swallow. Nature 379, 295, 1996.