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Why do we age?

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By Walter Pierpaoli, M.D.
Ed.- We welcome this comprehensive article from Dr. Pierpaoli. It covers in detail his long standing research into aging. Here he describes through his passion and dedication the trials and tribulations he has faced on the way, but fundamentally he describes his thoughts and ideas- all borne of his research and liaisons with many other leading researchers to the answer- why do we age?
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Why do we age?
The mythology and the dogmatic views of aging are based on the apparently inescapable fact that death is a "natural" conclusion of life and that a "disease" of known or elusive nature is preceding death. This attitude towards aging and death is an integrant part of all past and present societies, to the extent that all social and economic structures have been, and are now founded on the relatively rapid course of human life, with predictable "variations" depending on a large variety of socio-economical and environmental factors. In fact all research on aging has been based, not on the understanding of the causes of a disease-free death, but on the possibility to delay aging.   Our preliminary and largely incomplete work on the function of the pineal gland insinuated into us the idea that aging is solely a genetically inherited neuroendocrine "program" of certain structures in the brain, which are responsible, from birth to death, for the optimal maintenance of the body in relation to the variables of the environment in which we live. This environment is dominated by two principal elements, namely daily and seasonal changes of light and temperature. Our initial work on the beneficial, night administration of melatonin to aging mice and the pineal-young-to old pineal grafting demonstrate, in their experimental crudeness, that these interventions dramatically affect the health conditions and the life span of the animals. Our present conclusion is that an enormous amount of work is now needed to better understand our findings because the most obvious information is still missing.   Man is a "product" of evolution on the planet Earth and the duration of his life is a part of the neuroendocrine program which evolved as an adaptive process to circadian and seasonal variability, to comply with Nature's needs, whose aims are beyond our comprehension, but certainly did not consider our longing for a long and healthy life!   The more I read about aging, the least I understand its attributes, which are predominantly sociologic rather than biologic. First of all, the conviction that "physiologic senescence" is a kind of inevitable and inescapable fact of life such as growth and puberty, precludes a priori to us a different view of aging. In fact we are psychologically incapacitated to see what is in front of us, namely a genetically inherited and evolutionary rooted program in the brain and in the neuroendocrine system which must be understood before we can interpret and possibly modify it. This inability to develop a new view of aging is an innate mental inertia which escapes any "logic". The worst enemy of life and health is the myth of aging! If we possess a "genetic program" for growth, puberty, procreation and aging, the expression of this program is certainly interpretable and amenable to an external modulation. This is perfectly feasible exactly like the interference with growth and puberty, where Nature offers us many natural models in animals and man. If  puberty can be delayed or accelerated, so it is for aging which is, in its typical expression, a progressive decay of central, adaptive neuroendocrine functions resulting in metabolic diseases,  immunodepression and cancer.

I wish to summarize here the leading elements of the conceptual basis and of the experimental models which have demonstrated the aging-postponing effects of administration of melatonin in the nocturnal hours in old mice and rats, and the even more remarkable capacity of a pineal gland from younger donors to prolong the expected life span in pre-senescent, older mice and rats, when it is transplanted into the recipient's thymus. No details will be described and the reader can refer to the literature (6, 9, 10-13, 16-19, 23-25).


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The neuroendocrine and the immune systems are interdependent
The interdisciplinary medical research now named "Neuroimmunomodulation" (NIM) emerged in the course of the last 35 years as an inevitable consequence of the demonstration that no separation exists, during ontogeny and embryogenesis and also in adult life, in the function of the brain, the neuroendocrine and the immune systems (3,9,14,15,20-22). As many like to describe it, they "talk to each other". The earlier studies carried out in many experimental and natural models, such as e.g. the neonatally thymectomised mice (14,15,20-22), the hypopituitary dwarf mice (3,14,15), and in particular the genetically thymus-less nude mice (10,15,21,22), all indicated that many hormones control immunity and also that immune cells affect the maturation and function of fundamental neuroendocrine  organs, both in the hypothalamus, in the hypophysis and in basic endocrine glands such as the thyroid, the adrenals and the gonads (9,14,15,20-22). In addition, it was observed that many natural or induced diseases or "syndromes" resembling a "precocious aging" in mice were closely linked to a derangement of the bi-directional regulation of the neuroendocrine and of the immune systems in the course of postnatal growth (21,22). It was thus progressively understood that some basic neuroendocrine alterations in the course of early life or, conversely, some missing cellular or humoral elements of the thymo-lymphatic, immune system during early ontogeny, were responsible for the emergence of physical and functional deficits which closely mimic "senescence" (21,22). This was also confirmed by studies with mice kept at a low caloric diet (8). The "story" of the work is now also summarized in a popular book (18). A number of data from our laboratory addressed us later to the  idea that the most crucial aspect of aging could be an aging-related, progressive blunting and finally abrogation of hormonal cyclicity, in particular of day-night circadian periodicity, a basic rhythm which determines the daily fluctuation of all hormones and all physiological functions, immunity, reproduction and sleep included (11-13,16,19,23-25). Our experiments considered the use of melatonin simply because some observations in athymic nude mice and in mice kept under permanent illumination for several generations had shown, in the first instance a reconstitution of immunity (10), and in the second case an impairment of growth, "runting" or "wasting" which closely resembled aging (7).   We started in 1985 the experiments which led  to the present evidence that in fact the pineal gland and one of its products, melatonin, play a fundamental role in the initiation and in the progression of aging (17,23-25).

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The pineal gland and "neuro-immunomodulation of aging": an inborn program
The three models developed in order to evaluate whether or not the progressive alteration of pineal function in the course of aging is in fact a possible cause of aging, were based on the consideration that if the pineal gland, thanks to its known bidirectional linkage with the entire neuroendocrine system, is the "master gland" of the body, its own progressive "aging" in the course of life may result in the de-synchronization of all functions and in particular of those metabolic pathways which maintain the integrity of the neuro-hormonal (endocrine) and of the immune systems. Although we still do not know why the pineal gland itself ages, we have demonstrated that the pineal gland and at least one of its products, namely melatonin, are key elements to start understanding why we age. It is in fact beyond any doubt that  a very significant aging postponing  effect is achieved in aging mice (and rats) with nocturnal administration of melatonin or young-to-old pineal grafting (11,12,16-19,23-25). However, an even more remarkable observation derived from the young-to-old and old-to-young, pineal cross-transplantation model, which revealed that an acceleration of aging is achieved when a younger animal is grafted with an older pineal gland after removal of its own pineal (6). This striking finding opened to us an unexpected field of investigation. It seems in fact that, after a certain age, the pineal gland actively promotes aging, as if the inborn program for pubertal maturation and reproductive function would inevitably lead to another step of the maturational events, namely aging.
This is even more evident if we consider that the implantation of a young pineal gland into the thymus of older mice does not result into any life prolongation if the recipient is too old (unpublished). It means that once the endogenous pineal has aged, no intervention can prolong life. There exists a critical age in pre-senescent or definitely senescent mice when both pineal grafting or melatonin administration affect positively the life span. But beyond a certain age, apparently the old mouse owns pineal determines itself the termination of life. This is clearly shown by the acceleration of aging in pinealectomized young mice implanted with an old pineal gland (6) but even if a normal; non-pinealectomized young mouse is implanted with the pineal gland from a very old donor mouse. This extraordinary observation forced us to recognize that there might exist a "death clock" in the pineal gland whose "program" cannot be modified unless the aging pineal is removed in due time and replaced with a younger pineal. We are thus in front of a completely new element for the evaluation of the causes of aging and of the significance of biological death. We can infer that the pineal gland, at least in our experimental models with rodents, is at the same time an "aging clock", a "life clock" and a "death clock", depending on its chronological stage frombirth to death. If this is the case, a large number of experiments are needed to assess these crucial temporary steps in mammals, man included. This is even more relevant than the further work aimed at the investigation of the mechanisms, or they should proceed in parallel with those studies. We are generally prone to study the details before understanding how the pineal gland itself, thanks to its links to the entire neuroendocrine network, programs aging. In the next section I will suggest some of the investigations which, in my view, must be carried out in order to decipher some basic aspects of pineal aging on the basis of our earlier and current findings.
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The rotation theory of aging: what needs to be done now?
Here are a few examples.

 A) Pinealectomy at different ages. If the pineal gland is a chronological scanner of growth, puberty, fertility and finally aging, we must perform extensive experiments of pinealectomy in rodents, in order to evaluate whether the consequences of pinealectomy will differ depending on the age when removal of the gland is performed. It is in fact obvious that the consequences of pinealectomy may be profoundly different or even negligible depending on the age and sex of the animals. We have observed that the thermocoagulation (cauterization) procedure is not adequate to remove the pineal gland. Surgical removal of the entire pineal gland with its stalk is mandatory and its complete absence must be confirmed at autopsy and by histological analysis. Other methods have given us contradictory and unclear results. Some preliminary results indicate that removal of the pineal gland in senescent animals may be beneficial. If this is true, it would confirm our concept that the pineal actively promotes aging when the "clock" of life has expired its genetically programmed cycle. A very extensive number of measurements must be carried out in order to evaluate the cause and the sequence of the derangements affecting immunological and neuroendocrine functions. It may be possible that pinealectomy at a young age does not affect the life span simply because compensatory mechanisms, (e.g. other sources of melatonin) adjust the body to the removal of the pineal. This could be completely different later in life or at the time of aging. The blunting or decrease of the night peak of melatonin in the course of aging could be only a signal of pineal aging and the initiation of active death signals.

B)Pineal grafting in normal or pinealectomized, young, adult or older recipients. Experiments should be carried out in large groups of male or female mice and rats of different age, in order to evaluate if pineal grafting from a young or from an older donor into their thymus or under their kidney capsule would affect their aging. This approach would help understanding to what extent chronological aging of both the implanted pineal gland and of the grafted normal or pinealectomized young or old recipients, would delay aging and/or prolong their life span.

C)Multiple and repeated pineal grafting into aging, intact or pinealectomized animals. Pinealectomized and normal, intact aging mice and rats should be implanted into the thymus with a pineal gland from young donors and transplantation of  the young pineal from the young syngeneic donor should be repeated and a new gland grafted again into the thymus or under the kidney capsule of the same recipients about four-five months later. Grafting should be repeated again in case an aging-postponing effect is visible and measurable. This intervention could indicate if the limited duration of the aging-delaying effects of young-to-old pineal grafting depends on a progressive expiration, deterioration or aging of the intrinsic activity of the young, grafted pineal, which must be replaced with a new young pineal in order that the aging-delaying activity can be further prolonged.

D)Seasonal variability of melatonin administration. It is of paramount relevance to evaluate the aging-postponing effects of nocturnal administration of melatonin to old mice and rats in relation to the season. This is particularly easy in rodents, whose life span is about two-three years and whose physiology (immunity, hormonal and reproductive functions) is profoundly influenced by the season, in spite of their maintenance under constantly artificial conditions of light and temperature. Experiments should be devised where the animals are maintained from birth under natural seasonal variations of light and temperature, in special and protected (low-stress) cages where natural cyclicity of environmental factors is much closer to the conditions of wild animals. We have observed a striking, aging-delaying effect of melatonin when given during four winter months (from November until February) to aging mice (unpublished). Although these effects may not be so relevant in man, their interpretation would be very useful for improving the beneficial activity of nocturnal melatonin administration in man.

We just skimmed over the many, almost unlimited work which must be done before we can start to examine closely the mechanism of action of melatonin. It is in my view illusory the pretence to elaborate a "mechanism" until we have done the basic "dull" work which could clarify to us whether or not there is a centralized "aging and/or life clock" in the mammalian pineal gland which is amenable to a pharmacological or physiological modulation.
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What is aging?
If we restrict our analysis to the vertebrates, and in particular  to the mammalian species, we can clearly state that, notwithstanding the unforeseeable occurrence of  traumatic accidents  and the aging-accelerating effects of  social distress, of a large number of noxious environmental agents  and poisons, and  bacterial or viral diseases, aging is by itself a genetically programmed event for all species. In homeotherms, namely in warm-blooded vertebrates, we can predict a lifespan which is closely dependent on their genetic background. The question arises: why has a specific lifespan been established for a species? We are not going to answer this evolutionary question. Our curiosity concerns only the nature and essence of the "programmed clock" for all mammalian species, and the common pattern which characterizes the decay of biological functions which, in all species, is called senescence. In other words, we do not deny the importance, but we forget for a while the evolutionary significance of aging, to confine our attention to the nature of aging in order to delay, arrest or even reverse its course. We have no time for academic exercises! I would here restrict further the discussion to the evaluation of the sheer scientific hard facts concerning the presently known approaches to aging delaying interventions in mammals:

  • Restricted caloric diet
  • Exogenous administration of melatonin
  • Exogenous administration of melatonin and TRH

Over the course of many years, we have progressively developed and analyzed the concept and the experimental data underlying our claim that aging, similarly to somatic growth and fertility, is simply a pineal complex-driven neuroendocrine programme in the brain leading to progressive derangement and de-synchronization of fundamental neuroendocrine, hormonal regulation such as gonadal, thyroid, adrenal functions and others. In other words, the aging orchestra director delivers untimely and chaotic, haphazard messages and the whole orchestra gets deranged! Therefore, there is a common denominator for all the typical somatic and functional deficits of aging and the metabolic decay and dissociation of basic cell activities such as the oxygen-dependent energy production inside the cells. We think that the "program of aging," similarly to the "program of growth" is basically dependent on the close synchronic and mutually dependent relationship between, first the developing and later the aging neuroendocrine and immune systems, clearly exemplified, in the course of aging, by andropause and menopause. However, in the course of our studies, other elements have appeared of which the fundamental aspects of aging are: the neuroendocrine-immune interactions both during ontogeny of the immune system and during aging. The "talk" between the two systems is based on the molecules which provide to both reproductive functions and to maintenance of an efficient and self-monitoring immune network. In recent years, the discovery of transferrins as key agents for the maintenance of "self" identity has opened a new field for evaluation of the relevance of "self" integrity and for interfering with the program of aging. In fact, one could speculate that aging is by itself the progressive extinction of the capacity to distinguish between "self" and "non-self," namely to maintain self-tolerance. This is typically shown in the emergence of autoimmune diseases and cancer, which is progressive with aging. Here we can find an important link between the cross-talk between the neuroendocrine and the immune system, in which we have identified some key elements which all contribute to an efficient functioning of neuroendocrine and immune functions.
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Life prolongation via a restricted calorie diet (RCD)
Since the first dramatic experimental evidence produced by McKay with rodents an immense amount of literature is  now available which documents that the different methods used, all prove that a diminished calorie intake will significantly delay aging and the many aging related diseases and  metabolic dysfunctions. However, it has taken over sixty years before the National Institute on Aging started to evaluate whether or not a RCD applied to non human primates would also retard aging (sic). There is now evidence that this is the case and many results start now to be available from this long-term trial. At the time when the thymus was considered to be, thanks to its basic developmental functions in ontogeny, a kind of "clock" for aging of the immune system, we demonstrated in a rather neglected publication, that in fact the thymus does not deserve such a primary role for initiation and progression of aging. Removal of the thymus at different times after birth in mice, did not significantly affect their life span. However, it became clear that the thymus was deeply involved in the ontogenetic programming and maturation of the entire neuroendocrine system, and those athymic nude mice suffered a kind of precocious senescence, which couldbe completely prevented by thymic implantation. In fact, thymus grafting resulted into a complete normalization of neuroendocrine functions. On the basis of those findings and the consequent observations on the ability of mature lymphocytes to restore growth, immunity and to prolong the life of dwarf mice, the idea evolved that the different hormonal regulation would be responsible for the aging-postponing effects of a RCD. So we suggested that a decreased calorie intake would produce permanent changes in the central, hypothalamic-pituitary hormonal functions, thus maintaining the body at a more juvenile level of endocrine and metabolic regulation. This was particularly clear with regard to the sexual functions of rodents maintained on a RCD.   We conducted some experiments to demonstrate that if mice are kept on a RCD for a few weeks after weaning, and then fed again ad libitum, they maintain in spite of this normal feeding a permanently different pattern of hormonal regulation. This data confirmed that the feeding behavior at a time when the neuroendocrine system is still immature, permanently affects maturation and function of the entire neuroendocrine system. This observation is of course very relevant with regard to the onset of obesity in overfed children and the consequent irreversible derangement of their mature neuroendocrine and metabolic system. This environmentally induced obesity which is now so dramatically evident in the affluent Western Society is of course different from mild or severe fattening of "normal" metabolic aging in humans. Also, this environmentally acquired dietary obesity is different from genetically inherited obesity, which afflicts a minor number of families and individuals.

The clear answers from many studies all indicate that RCD produces juvenility-oriented and permanent changes of neuroendocrine regulation which are exactly the opposite outcome of environmentally induced and aging-accelerating dietary obesity. This hypothesis is documented later in the section concerning the anti-aging and obesity-curing effects of TRH.   If endocrine and metabolic dysfunctions are the expression of the programme of aging, and if the pineal gland is a "life and aging clock," consequently we must consider that RCD affects mainly the pineal gland and its functional state. This seems to be the case. In fact, it has been reported that a RCD maintains juvenile levels of melatonin both in rodents and in primates. In a collaborative project with Dr. George Roth and Mark Lane at the National Institute on Aging, Baltimore, USA, in which large groups of primates have been under RCD for several years, data are emerging that RCD very significantly maintains high levels of nocturnal melatonin in both male and female aging monkeys, comparable to the levels in young primates. Our conclusion is that a RCD, by setting the "neuroendocrine clock" at a more juvenile level, protects the pineal gland from aging and thus protects from aging the whole pineal-controlled hormonal, circadian and seasonal periodicity, whose progressive decay leads to aging.However, melatonin is only a signal from the pineal gland of an overall de-synchronization of the whole neuroendocrine network leading to a progressive alteration of hormonal cyclicity and, consequently, of surveillance, immune functions. At the basis of this central, pineal-directed aging, lies TRH, a pineal peptide which is responsible for the aging-postponing effects of young-to-old pineal grafting (see below).
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The anti-aging molecule melatonin
In spite of the vulgar defamatory campaign and plot against the anti-aging properties of melatonin, it is beyond any doubt that exogenous administration of melatonin to aging rodents postpones their aging and/or prolongs their life. Unfortunately, for mysterious or tactical reasons, those experiments have not been properly replicated while the deceptive behavior against melatonin anti-aging properties continues. Of course, melatonin served to indicate that the pineal gland is deeply involved with the aging process. It suggested the pineal grafting experiments, which disclosed a dramatically new approach to aging postponing strategies. Also these fundamental experiments have not been replicated, although they may be now in course, several years after their initial publication. The pineal grafting experiments also served to indicate that the pineal gland, via its links to the entire neuroendocrine system, controls the "program of aging" and that an aging pineal can accelerate aging even in a normal young animal carrying his own young pineal. These striking observations helped to understand that other key mechanisms and/or molecules must be operative for the anti-aging and the aging-accelerating properties of pineal grafting. Whether or not the anti-aging and the pro-aging capacities of the young and old pineal gland depend on a unique mechanism, it is reasonably clear that pineal components, such as TRH, play a basic role. That melatonin could significantly postpone aging thanks to its anti-oxidative and hydroxyradical-scavenging properties, such as those of vitamin E or glutathione, is not supported either by logic or by any serious in vivo confirmation. It does not seem that the many receptor-mediated effects of melatonin and the myriad of affinity binding mechanisms can explain its anti-aging properties. The anti-stress, immunoenhancing effects of melatonin show in fact a rather slow "buffer" mechanism. This reinforces our hypothesis that melatonin does not by itself exerts the activities observed but rather protects the pineal gland from aging. Nocturnal melatonin supply will not protect from aging when the age of the animals is too advanced. This has now been proven in another kind of placebo-controlled clinical trial, in which perimenopausal women aged 40 to 60 years, have been treated with melatonin. Already after six months the evidence emerges that younger women are more susceptible than older women to the anti-aging properties of melatonin. This fact strongly supports the view that the beneficial and pineal-protecting effects of melatonin are more pronounced at a time when the pineal is still relatively young. This unexpected finding indicates that melatonin can exert a more pronounced anti-aging effect if the administrations start rather early in life, in so far it protects the pineal from aging. This observation is fundamental for the prophylactic use of melatonin in anti-aging interventions and strengthens the suggestion that the mechanism of action of melatonin cannot be attributed to a "hormonal" effect on specific receptors but rather to a relatively simple night saturation of melatonin content in the pineal gland, and consequent abrogation of night endogenous melatonin production.    If this suggestion is true, it must be possible to  drastically reduce or abrogate  aging-dependent endocrine and metabolic dysfunctions by the administration of exogenous melatonin  in the early, post-pubertal  life of mammals, man included, as hinted by the recent striking results in perimenopausal women  treated with melatonin for six months.
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The anti-aging molecule thyrotropin releasing hormone (TRH)
A decade ago, in the course of studies on the stress-protective and antiviral effects on melatonin, the possibility was considered that melatonin may exert its effects through the thyroid gland, by enhancing synthesis or secretion of thyroid hormones, which are known to be potent immunoregulatory agents. When we analyzed the effects of TSH and also of TRH, we saw that TRH was perfectly able to mimic and even to increase the effects of melatonin. Further studies showed that the effect of TRH is obviously non-thyroid-mediated. Also later studies demonstrated that a discrete lesion of the anterior hypothalamic area in mice, which produce electrolytic damage of the "thyrotropic area" which is known to contain high affinity receptors for TRH, resulted into a rapid involution of the thymus and a sharp decrease of peripheral lymphocytes, which could be restored with TRH treatment. Those early data disclosed the unsuspected role for TRH in the regulation of immunity and also a most remarkable effect of TRH in the restoration of normal levels of lipids in the blood of aging rodents. Those results suggested a key role for the tiny peptide TRH in the anti-aging effects of both melatonin and young-to-old pineal grafting. It was hypothesized that it is in fact the ubiquitous tripeptide TRH, highly concentrated in the pineal gland, which is responsible for the anti-aging effects of circadian administration of melatonin. In fact, the effects of TRH are by far more rapid than those of melatonin, in particular in the restoration of lipid levels. A posteriori, it seemed most obvious that TRH is in fact responsible for the effects of melatonin and pineal grafting. TRH is ubiquitous in nature and its mechanism may be linked to basic cells functions. Without entering into discussions about its mechanism, we studied the long-term effect of a combination of TRH and melatonin in old, aging mice, in order to see if both agents together are able to further delay aging and /or prolong life. It was shown that the combination of both melatonin and TRH significantly enhance the anti-aging effects of melatonin. It was also evident that the effect of the combination was not due to a chronic stimulation of thyroid hormone secretion. As hinted long ago, we can assert that TRH is in fact a main agent in the pineal gland, in the brain and in other cells, which possesses the unsuspected properties of a potent aging-reversing molecule. The metabolic effects of TRH in the normalization of cholesterol and triglycerides are amazing. We dispose now of a new natural and evolutionary ancient molecules for efficient anti-aging interventions. The mechanism for the rapid metabolic effects of TRH is unknown. We think that the reason for its old or acquired anti-aging or rather rejuvenating properties must be sought in the evolutionary history of TRH and in its key role in basic metabolic pathways.
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Conclusion
Life from chaos: the haphazard patchwork of Nature for survival of the species. The cause of aging is simple: it is a program in the neuroendocrine system and it is independent from diseases. We age exactly the way we grow and stop growing. The program is genetic for man, dog, pig, mouse, but we have the capacity to learn how to change, not the genetic program, but the way and time of its expression. We can slow down aging, we can stop aging. We can reverse aging and restore youth in so far no permanent damage of brain tissue has occurred. We will learn to see it in the course of the next few years, when the results of our capacity of resetting the periodicity clock will be visible. Our way of resetting the central clock now is very primitive and empiric, but we shall learn progressively to be more knowledgeable and clever, more cautious and sophisticated, we shall use the ways of nature and the clever natural way: no jogging, no aerobic, no stretching, no fanatic dieting, simply with readjusting the body rhythms to those of the planetary system, namely the sun, the moon, the seasons, the day-night cyclicity. We age simply because we inadvertently lose the adaptation capacity to be and to remain periodical and cyclical; we de-regulate our neuroendocrine system and become refractory to the laws of natural cyclicity.

Typical examples are menopause and andropause: they are indicators of loss of periodicity: lack of periodicity is death. When we stop rotating around the sun, we die. Our body becomes insensitive to the basic impulses and messages from the cosmos, we de-synchronize and become cosmic dust, the way we were for eons. Immortality is not a myth: it is simply a permanent re-adaptation to sun and lunar cyclicity. Now we know to way to go and this aim we could achieve within a few years without the prejudice and arrogance of the "saviors."

The amazing array of molecules in the living body makes any classification illusory and even extravagantly ridiculous. Every day new molecules are "discovered" and new functions for them are revealed in the scientific journals. The reductionistic approach to science, medicine and health care has created a true Babylonian communication barrier between researchers of different disciplines to the extent that intercommunication is totally barred. Apparently, we know almost everything but yet we find daily something new. This situation does not accelerate knowledge; it only retards the most obvious interpretation of Nature's laws. For any scientist, it is even impossible to define himself and to indicate the direction he is going. Universities and schools have missed their aims and yet nobody seems to have noticed it! We go on identifying thousands of new molecules in the body and in Nature, yet we cannot anymore link them into a logic framework for function. The fact is that logic and integrative knowledge requires nowadays such a huge integration of notions that, I am sure, even Leonardo da Vinci would be confused! Yet, in spite of this inextricable and hopeless lack of understanding of basic biological processes, we function! The miracle that we function is in front of us and the regenerative capacity of Nature is beyond imagination.

I am convinced that we are at the bottom of a hole. We possess an unbelievable amount of notions, yet we fail to pose them in the right place: there may be not place for notions, only for concepts! The mechanistic approach to problems has only created a huge number of new questions without answering any of the already existing questions. In the medical research field, there is no cure or prevention for cancer and aging related degenerative diseases, there is no cure against many viruses.  The so-called cure is often palliative and the stressful and overpopulated world creates new pathologies.  We did not move a bit from 1940 as far as the understanding of biology and the laws regulating the body in the planetary system in which we live and daily rotate. In this apparently rationalistic system, only the secretive laws of chaos may simplify our search for mental and body health and the balance of body and soul. I would start not from the Cosmos, but simply (and more modestly) from the planetary, solar system.

The insensitive, are active, feeble, fragile, erratic, shivering and apathetic "old man" is the living example of "something"  between self and not-self, where the mind is the psychic counterpart of a degrading body which has lost the capacity to recognize and maintain itself in the hostile environment.

The progressive deterioration of the senses and also the loss of libido represent a passage from perception and also enjoyment of body's sensorial capacities (odors, sounds, visual stimuli, sexual arousal and temperature changes) to a state of often unconscious and relentless decay of self-consciousness towards total acceptance of the "laws of nature" and the programmed death. Although this view is evolutionarily understandable, its interpretation allows now to drastically deviate from its dogmatic, non scientific and deep-rooted social structure towards a limitless freedom for human kind.  

Why do I worry about of my own aging? It is only a curiosity of life! It is simply to make more time available to escape the traps, not of Nature, but of man-generated confusion.
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Disclaimer: The information presented herein strictly reflects the opinion of Prof. Walter Pierpaoli and is intended to provide information and for educational purposes. The information herein intends to support, and not replace, the existing relationship between a patient/visitor of this website and his/her referring physician and, in no case, can it be considered a diagnosis or used as an alternative to a medical examination. Prof. Pierpaoli undertakes no responsibility for any health consequences of any person who reads and follows the information contained on this site. All readers of the contents on this website, especially those who take prescription or over-the-counter drugs, should consult their physicians before beginning any nutritional or supplemental program or prior to making lifestyle changes. The contents herein are in compliance with the guidelines relevant to the application of arts. 55, 56 and 57 of the new Code of Medical Ethics and are intended for the general public.