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Gerontological Manifesto

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The Gerontological Manifesto

By Alexey Olovnikov, PhD

The necessity to create various remedies for degenerative age-related diseases is beyond any doubts. But this process is somewhat like a Sisyphean task, because the aging of each person only deepens over time, persistently destroying the results of treatment. Pharma is forced to deal with the countless consequences, rather than with their cause. The primary cause of aging is still deeply buried in gerontological terra incognita. Meanwhile, a growing and imminent new threat for humankind is becoming increasingly apparent. This threat is the increasing aging of the human population as a whole. The menace to the society is in the ongoing change in the ratio of the able-bodied and the disabled-bodied populations in the advanced countries. This trend may lead to the numerical superiority of disabled old persons already by the middle of the 21st century. According to the current estimates, the medical expenses on non-communicable diseases for the period 2010-2030 will be $47 trillion by 2030, with two thirds of this sum to be linked to the costs of the elderly healthcare. ( A solution to this problem by attracting young migrants only shifts the burden of care to the countries of exodus. If no action is taken to radically enhance the ongoing studies in the field of aging biology, this problem will became a burden unbearable for our civilization: Humanity will not be able to maintain the elderly people! The solution to such a gerodemographic situation, the potentially fatal and vitally important problem, can be achieved only through a radical slowing down of the pace of the aging process, or by stopping it! And this can be done only via the discovery of the primary causes of aging that still remain elusive. The search for medicines against degenerative diseases of aging and the studies of the primary mechanism(s) of aging are two related but clearly independent tasks. The striving to the radical slowing down of aging is as important today as the struggle against infectious pandemics was in the past. Even under the most favorable scenario, several decades will be spent until finding the conditions for the radical slowing down of mammalian aging (and for the subsequent translation of the results to the clinic). But within the next several decades, the number of disabled elderly people in the developed countries can exceed the number of able-bodied adults. The favorable resolution of this unprecedented historic challenge can be found only in case of the unprecedented concentration of intellectual and financial efforts in a new life extension project. The enemy, that has quietly crept up onto our civilization, is quite capable of either destroying the basic moral values (in the way of forced absence of care for the elderly), or undermining the financial foundations of the society (in the way of the back-breaking costs of servicing the elderly). A more likely scenario is that it will do both! The non-biological alternatives to the ongoing efforts in biology and medicine are the robots, but they are not ready to take the frail portion of mankind on their iron shoulders. But even with the robots, the humans would hardly have forgotten their oldest dream – the dream of a significant life extension. Non-aging or delayed aging in essence means the potential for a very long healthy life. A potential critic may argue that a very long healthspan will lead to overpopulation. However the answer to this objection is known. The experience of birth control on the large state scale has already been gained, albeit with other goals. It is of course possible to leave everything as it is, so that life itself will put everything in its place. Life will do it, but at the cost of mass misery and huge losses. Are those necessary or can be avoided by human effort?

And finally we should note one of the most formidable companions of aging – cancer. It is known that, after sexual maturity, cancer incidence increases exponentially with age (de Magalhães JP. How ageing processes influence cancer. Nat Rev Cancer. 2013 May;13(5):357-65.). Why? According to a widespread view, occasional changes in chromosomal DNA accumulate as long as there will appear some fatal mutations. However, there are some facts that do not fit into such a simple scheme, and therefore, a generally accepted theory of cancer origin is still absent. There are reasons to suppose that the genuine cause of this multiform pathology is the non-mutational flaws in the functioning of a special, so called chronographic, mechanism. This hypothetical mechanism directs the timely sequential changes of the body structures (hence, it directs the control over the biological age of an individual organism) in the course of the development, maturation and aging of multicellular organisms (Olovnikov A.M. Chronographic Theory of Development, Aging, and Origin of Cancer: Role of Chronomeres and Printomeres. Current Aging Science, 2015, Vol. 8, No.1, 76-88.). Non-mutational errors, which rarely occur during the functioning of this mechanism changing the age, can lead to a loss of proper genetic control in some cells. Only after that, the progeny of these cells begins to obtain and accumulate mutations which eventually can give rise to a malignant growth. If so, the delaying of aging can bring another nice bonus – the prevention of cancer. The sooner we will get this bonus, the better for all of us.

Alexey M. Olovnikov

January 19, 2016

alexey-olovnikov2 Alexey Matveyevich Olovnikov, PhD, Institute of Biochemical Physics, Russian Academy of Sciences.

In 1971, Olovnikov was the first to recognize the problem of the DNA end underreplication and to suggest the telomere hypothesis of cellular aging and the relationship of telomeres to cancer. In more details: 1) He predicted telomere DNA shortening during normal cell doublings and foretold the correlation between telomere length and the cell doublings potential, or Hayflick’s limit; 2) He predicted also the existence of a compensatory DNA polymerase responsible for maintenance of telomeres (now the compensatory enzyme is known as telomerase); 3) He supposed that cancer cells should have the same compensatory DNA polymerase (telomerase) as the  germline cells, and assumed that this enzyme endows cancer cells, like the  germline cells, with their immortality; 4) In addition, Olovnikov interpreted a circular form of bacteria’s genome as a means of protection of their DNA from shortening.

History has shown the validity of these basic predictions and explanations that were made by Olovnikov at the tip of a pen and essentially began a new area of research. Later, other researchers, for their experimental demonstration of how chromosomes are protected by telomeres and the enzyme telomerase, were awarded the Nobel Prize (2009).

Currently, A.M. Olovnikov is elaborating a new “Chronographic Theory of Development, Aging, and Origin of Cancer”, positing a critical role of new hypothetical organelles – chronomeres and printomeres –  in these processes. According to this theory, aging of a multicellular organism is caused by the stepwise programmed loss of chronomeres, whereas senescence of dividing cells is associated with the shortening and loss of printomeres. Both printomeres and chronomeres are small perichromosomal amplificates of the regulatory segments of chromosomal DNA, and they encode regulatory RNAs. Chronomeres are located in neurons of brain’s chronograph, or a specialized clock, which records the lived time in the form of nonrandom changes of body structures. According to the new theory, in the future, the key techniques to postpone organismal aging and to stop tumor growth could be: 1) a stopping of the pacemaker of the biochronograph mechanism, and 2) a forced regeneration, or re-synthesis, of chronomeres and printomeres.



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