Walter Pierpaoli President, INTERBION Foundation for Basic Biomedical ResearchCH-6826 Riva San Vitale
Notice: this article has been assembled only for those non-specialists able to appreciate its simplicity and not for those "experts" whose obnubilated mind allows no penetration of the simple and smart laws of Nature
My mother-in-law Emmy Hugly, living in Horw near Lucerne in Switzerland, is now 94 year-old, perfectly healthy and Parkinson-free in the last 15 years, with no intention to give up! Her story is narrated shortly in the "Melatonin Miracle" (1) and also in my recent book published in Italy "120 and longer, average" (2). She runs shopping every day, and when we celebrate her birthdays, she loves dancing and playing the piano. I am used to visit her from time to time and make a record of her health and behavior with a video-camera. She would love to see visitors and journalists coming to her home. They will be enthusiastically received! She will prepare for them excellent tea and serve with no shaking hands, as was the case 20 years ago, when she had severe and rapidly worsening Parkinson. Emmy is undoubtedly the longest melatonin-taking person in the world. She started in the early 80th of the last century, when 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 or/and consequent life prolongation. She asked me to give her the "pills" and she religiously followed my prescription. Twenty years ago I prepared for her in my lab 3mg melatonin capsules. Of course, she is now taking magic Melatonin Pierpaoli with zinc and selenium, as a kind an "evening rhythus" every night. The enbittered adversaries of innocent melatonin should visit her before their life program has expired! Of course the lesson we can learn from Emmy is what I was repeating in my "shout in the desert" Conferences (3-5): 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! Lucky 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 born old and permanently old and aging until the "liberation" of death.Of course now many follow Emmy's virtuous path, regaining vitality every day, month and year.
Aging is simply a neuroendocrine program in the brain!In fact: 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 ciclicity, from fertilization of the egg until the last breath of life. Being life on our planet 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 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 in fact known 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 (8,9)? I do believe 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, spreaded injury and false news by hiding behind the sheltering curtain of "prestigious journals" (10,11). Their behaviour must be condemded and made public because their irresponsible and irrational attacks have produced an awful damage to millions of persons around the world.
Why Does Melatonin Prolong Your Life?
Melatonin prevents aging-related diseases, delays your aging, and automatically prolongs your life by simply impeding and postponing the progressive central, hypothalamic alteration of feedback hormonal regulation, as described beautifully by 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 "do not work"to the pineal, not only protects the "central hormonal director", but even 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 the grafted pineal unable to produce itself melatonin because it is dissected from its neural connections, obviously the central "life clock" is located in the pineal itself but its mechanisms do not depend on melatonin! The aging pineal in fact loses its ability to produce a night peak of melatonin, being this a clear signal of its own aging. Therefore we have now shown beyond any doubt that exogenous melatonin, by protecting pineal aging through its positive feedback on the pineal itself, 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 yhe pineal is 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 exogenous melatonin starting early in life, will inevitably maintain youthful conditions and avoid emergence of all kind of diseases. Even under the stressful conditions of life to day 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 prevent all of them and, once 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 make it suitable to delay and even arrest the course of the disease, be it a neurodegenerative disease (such as Parkinson, multiple sclerosis etc.), cardiovascular diseases of all kind and finally cancer. This olistic concept of medicine has now found its biological and clinical 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 from 42 until 62 years of age, showing 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 be able to announce the news to all women, but not for a long time! To our great astonishment and dismay, four different journals treating the theme (Menopause, European Journal of Obstetrics and Gynecology, The New England Journal of Medicine and finally Steritity and Fertility) refused to publish our results! The 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 have no space enough! I was silly: 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?In fact 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 appaling story shows that the enemies of melatonin are everywhere and that a true discovery meets with fierce opposition, but how long?
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 was used to say the great scientist Sir Peter Medawar, whom I knew and met many years ago: "it is not molecules which evolved but simply the use to which they are put". This means to me that also 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, being melatonin a very ancient molcule 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!Thefore 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 next year, is a suitable place to unveil this new dimension of life and death in order that we can better adapt to the sad destiny of mortal mammals. After all, death at a very old age without diseases, not yet immortality, 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 complication of nature and not its logic interpretation is the current fashion. Being the gap between those who understand and the stubborn opponents widening every day, let us wait and see. We are far ahead "beyond melatonin" in so far melatonin succeeded in lighting our brain, enabling us to escape the traps of reductionistic "modern science". At the same time the use of melatonin protecting our pineal and prolonging our disease-free life, allows us more time to understand and to apply, to severely ill persons, the blessing of our New Innovative Medicine also by making use of those molecules emerging from the brain "swamp" which, such as 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 this is another story.....
References 1) W. Pierpaoli & W. Regelson, with Carol Colman: The Melatonin Miracle. Nature's Age-Reversing, Disease-Fighting, Sex-Enhancing Hormone" . Simon & Schuster,New York, 1995 (translated into 17 languages). 2) W. Pierpaoli & Pippo Zappulla: 120 and Longer, Average. Vivere Bene, Invecchiare Giovani e Morire Sani. Chrono-Med, Collana Arcadia, Brescia, Italy, 2003. 3) 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. 4) 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. 5) W. Pierpaoli, W. Regelson & N. Fabris, Editors. The Aging Clock. Third Stromboli Conference on Aging and Cancer. Ann. N.Y. Acad. Sci. 719, 1994. 6) A. Montagu: Growing Young. McGraw-Hill Book Company, New York, 1983. 7) W. Pierpaoli: Integrated Phylogenetic and Ontogenetic Evolution of Neuroendocrine and Identity-Defence, Immune Functions. In: Psychoneuroimmunology (R. Ader, Editor), Academic Press, New York, pp. 575-606, 1981. 8) 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. 9) 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. 10) F.W. Turek: Melatonin Hype Hard to Swallow. Nature 379, 295, 1996. 11) S.M. Reppert & D.R. Werner: Melatonin Madness. Cell 83, 1050, 1995. 12) V. M. Dilman: The Law of Deviation of Homeostasis and Diseases of Aging. H.T. Blumenthal, Editor. John Wright PSG, Inc. Boston, 1981. 13) W. Pierpaoli & V.Lesnikov: Theoretical Considerations on the Nature of the Pineal "Aging Clock". Gerontology 43, 20, 1997. 14) W. Pierpaoli: The Pineal Gland: a Circadian or Seasonal Aging Clock? (Editorial) Aging 3, 99, 1991. 15) W. Pierpaoli & D. Bulian: The Pineal Aging and Death Program. I. Grafting of Old Pineals in Young Mice Accelerates their Aging. J. Anti-Aging Med. 4, 31, 2001. 16) W. Pierpaoli & G. Maestroni: Neuroimmunomodulation: some Recent Views and Findings. Int. J. Neurosci. 39, 165, 1988. 17) W. Pierpaoli, H.G. Kopp, J. Mueller & M. Keller: Interdependence between neuroendocrine programming and the generation of immune recognition in ontogeny.Cell. Immunology 29, 16, 1977. 18) G. Bellipanni, P. Bianchi, W. Pierpaoli, D. Bulian, & E. Ilyia: Effects of Melatonin in Perimenopausal and Menopausal Women: a Randomized and Placebo-Controlled Study. Exp. Gerontology 36, 297, 2001.