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Evidence for a pineal-directed aging program. Its control and clinical interventions.

The many theories on the nature and origin of aging clearly show that we did not know what is aging and what it means. However, there cannot be many kinds  of "physiological" aging, but only one! The many claims and dissertations of the advocates of many hyphoteses on the nature of aging are not supported at all by the "hard facts", namely in vivo evidence in mammals and man! To my knowledge, aging can be remarkably postponed, but not reversed, only  by   A) a pre-puberty or permanent restricted caloric diet (RCD)  or by B) nocturnal supplementation of melatonin or, in rodents, by young-to-old pineal grafting. Both procedures, RCD and nocturnal melatonin supplementation, result into the same protecting effects on the pineal gland, which preserves its juvenility and the capacity to monitor and maintain indefinitely its role as "director of the hormone orchestra". To state it once more, the progressive levelling of the night peak of melatonin during aging is only a signal for aging of the pineal gland itself! Therefore night melatonin supplementation serves only to protect the pineal gland from aging by providing the "finished product" of the pineal gland itself. This is not a hormonal feed-back mechanism, but simply a retroactive action of melatonin which avoid to the pineal the task of producing melatonin by acetylation and methylation of the precursor serotonin. The evolutionary task of the  "pineal network" is in fact by far more complex that simply the production of melatonin! The "clock" is dense with extremely important and biologically active agents! The observation that the "central pineal network" controls our relation to the internal and external environment and adaps the body to the many daily and seasonal variables and influences,  derives from experimental work which started in the early 60th when the medical disciplines now called "Neuroimmunomodulation" or "Psychoneuroimmunology" initiated with the demonstration that a link exists between the thymus (the master immune organ) and the hypophisis (the master endocrine gland) and that  a bidirectional channel joins the neuroendocrine and the immune systems. However, at that time, the basic notion was missing that the quantitative aspect of immune capacity and of hormonal levels are irrelevant for the equilibrium of the body if we do not maintain and restore the fundamental day-night rhythmicity of all physiological functions, according to the periodicity of the planetary-solar system. With other words, my "discovery" simply disclosed that it is not hormones and cells which matter, but their constant and cyclic inter-synchronization between each other. With simple words, we function as long as our body keeps its ability to adapt to the environment and  to its natural rhythmic fluctuations according to day-night cyclicity and to seasonal variations (temperature, light, humidity, electromagnetic field and so on) and can thus oppose the many noxious assaults of bacteria, viruses, and social environmental agents (noise, pollution, distress etc.). It is in fact the daily cyclicity of hormones which strictly controls immunity and the expression of all immunological, surveillance functions!However, the "clock" regulating our "life, aging and death program" cannot be confused with the diseases  accelerating aging and hiding its true nature. Diseases of all kind are in fact only the expression of a central neuroendocrine alteration of the "clock", delivering wrong and false signals to the systems regulating resistance to infections, non-proliferation of dormant preneoplastic cells, and the hormonal-metabolic pathways which control cells respiration and membrane permeability. All neurodegenerative and autoimmune diseases, cardiovascular diseases and cancer derive from the same, identical and basic, central derangement of  the control of hormonal, day-night cyclicity. That the basic element of biological integrity depends on the "biological clock" in the pineal network has been demonstrated by the cross-transplantation experiments in rodents, which have provided the clear-cut and definitive proof that aging of the pineal gland itself is leading to progressive or accelerated  aging and that only a protection of the pineal gland from aging results into a postponement of the aging process. I have thus provided incontrovertible evedence that aging is a program in the pineal network and that protection of the pineal gland from aging results into prevention of aging and in particular of aging-related diseases.It is not my aim to expose here in detail the massive investment of work and experiments in forty years, which led to the discovery of a "life, aging and death clock" in the pineal network. I will however comment on the clinical and therapeutical significance of the application of those principles to the prevention and cure of diseases and consequently to the expression of a disease-free aging program.As an example, the clinical work conducted by us  has shown that nocturnal administration of melatonin, by protecting the pineal gland of perimenopausal and menopausal women, prevents and corrects,  and even reverses aging of the reproductive tract of women in the most amazing fashion. All problems related to pre-menopause and menopause are massively eliminated with restoration of fertility and disappearance of neurovegetative symptoms. Silent or overt thyroid deficiencies have been corrected. This served to provide evidence that women' fertility and healthy life can be prolonged without any hormonal replacement. Menopause is in fact a typical expression of  programmed aging in the pineal of women!  Lunar cyclicity of their menstrual cycle is in fact abrogated!I also mention here my recent unpublished work with patients affected by neurodegenerative diseases such as Parkinson and multiple sclerosis,  where interventions aimed at a restoration of pineal function have resulted into potentiation of immunity, blockade of disease progression, restoration of lost neural functions and progressive elimination of nerve damage and degeneration. Work is in progress  to  establish  the basic principles underlying my approach to the therapy of cardiovascular diseases (the metabolic syndrome X), latent or  overt autoimmune diseases such as autoimmune thyroiditis, lupus and others.
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Pierpaoli, W. Neuroimmunomodulation : an approach to therapy of neurological diseases. In: Clinical Neuroimmunology, pp. 500-505. (J.A. Aarli, W.M.H. Behan and P.O. Behan, Editors). Blackwell, Oxford, 1987.Pierpaoli, W. And Regelson, W. The pineal control of aging. The effect of melatonin and pineal grafting on aging mice. Proc. Natl. Acad. Sci. USA 91, 787-791, 1994.Bellipanni, G., Bianchi, P., Pierpaoli, W., Bulian, D. and Ilyia, E. Melatonin in perimenopausal and menopausal women: a randomized and placebo-controlled study. Exp. Gerontol. 36,  297-310, 2001.Pierpaoli, W. and Bulian, D. The pineal aging and death programme. I. Grafting of old pineals in young mice accelerates their aging. J. Anti-Aging Med. 4, 31-37, 2001. Pierpaoli, W., editor. Reversal of Aging. Resetting the Pineal Clock. Fourth Stromboli Conference on Aging and Cancer. Ann. N.Y. Acad. Sci. 1057, 2005.
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