Astrocytic hypothesis
The astrocytic hypothesis of ageing of mammals (briefly the astrocytic hypothesis) suggests that ageing of mammals is a genetic disease that causes death, caused by the aromorphosis (evolution towards organization) in the theriomorph lineage of the vertebrates: the transformation of radial glia cells into star-shaped astrocytes during postnatal development, i.e. the disappearance of radial neuroblast migration from proliferative zones to the sites of their ultimate localisation in the brain of adult individuals.
The astrocytic hypothesis was proposed by Ukrainian biologist Olexiy Boyko in 2000, published in 2004, and finalised in 2007.
Prerequisites
The astrocytic hypothesis appeared during a systemic crisis in ageing biology and gerontology, when the old principles of conceptual models of ageing, which came to absolutisation of some phenomena and private mechanisms of ageing, fail. In other words, it became clear that theories of ageing have no ability to predict on the background of how even well known scientists offer a paradigm shift in aging biology.
More moderate views are proposed by O.G. Boyko (the author of the astrocytic hypothesis) that the time of its appearance coincided with the completion of verification of most ageing hypotheses, which directly link specific cellular processes with the initial cause of the ageing in the whole organism.
Their failure in this respect confirmed the existence of a species of multicellular animals (Metazoa) with negligible senescence (non ageing), that do not preclude any generation of reactive oxygen species or shortening of telomeres, apoptosis or other cellular processes, which typically account for ageing. This fact is not surprising, as pools of cellular mechanisms in both ageing species and Ageless species of Metazoa are virtually indistinguishable. Also rejected was the traditional view that mortal genes (ageing and death) appeared simultaneously with the appearance Metazoa and distribution functions between tissues, as are details AbOUT the existence of not only the species of multicellular animals Metazoa with negligible senescence, but also potentially immortal species of Metazoa. A good example is an individual of Antarctic sponges Scolymastra joubini, whose estimated age is from 15 to 23 thousand years. Finding the root causes of ageing has moved from the cell level to the organism level. Researchers have begun to compare the evolutionary design (species-specific features of anatomy, morphology, physiology, etc.) of ageless, ageing-slowly and rapidly-ageing animals. One of the results of the search is the astrocytic hypothesis.
Contents of the astrocytic hypothesis
The astrocytic hypothesis is based on common knowledge that in vertebrates (Vertebrata) the place of generation of neuroblasts in an adult, as well as in an embryonic phenotype, is separated from their final localization. Bear in mind that the adult phenotype, in this case neuroblasts, are produced in the ventricular / subventricular zone where neural stem cells have persisted into adulthood, then migrating a long distance along fibers of radial glia (except for mammals).
About 80–90% of neuron precursors in mammals migrate along radial glia fibers (which represent clues of the direction of this migration) during neurogenesis in a brain. But radial glia cells are kept for life against those vertebrates (in which neurogenesis in adult individuals is observed). In mammals, after the period of neurons migration, the radial glia cells are transformed into stellate astrocytes (except for the hippocampal dentate gyrus).
In other words, the disappearance of radial glia cells in the postnatal period of development prohibits physiological and reparative regeneration of nervous tissue. Therefore, "a postmitotic brain", where neurons are not updated pool for life, is a unique phenomenon among vertebrates and specific only to mammals. Convincing data, especially Jonas Frisen and Ellen Heber-Katz again demonstrated that the mammalian body part that is not updated during the life is only nervous tissue (brain)—specifically, the neurons that are its building blocks.
The astrocytic hypothesis suggests that the ageing of mammals is a genetic disease that causes death. Its cause is acquired in the evolutionary process of the theriomorph lineage of the vertebrates (aromorphosis): radial glia cells transform into stellate astrocytes in the postnatal period of development, i.e. evidence of the disappearance of embryonic radial migration of neurons from proliferative zones to the places of their final localization in the adult brain.
The astrocytic hypothesis in popular-science literature and media
The astrocytic hypothesis described in popular-science form by Elena Naymark, Rosa Barsova and Cyril Hryschenkov, scientific observer of the magazine 7 days (Moscow, Russia). In the media, and on its website, the astrocytic hypothesis is promoted professionally by the known Russian gerontologists Boris Kaurov. The astrocytic hypothesis appears in the Journal of General Biology accompanied by publications in the media and scientific press. The article by G.A. Tarasevich, "We could live to be eternal. Only nerves prevent it", argues that the Boyko astrocytic hypothesis is actually an advanced version of the elevation hypothesis of ageing by Vladimir Dilman. With publications in the scholarly-press-attractive paper "Reason For Mammals' Aging Lies In The Brain", articles about the astrocytic hypothesis appeared in some encyclopedias.
Criticism
Moskalev A.A. (Institute of Biology, Komi Scientific Centre, Ural Branch, Russian) presents facts and arguments against the astrocytic hypothesis. In particular:
A. A. Moskalev's arguments should be interpreted in two ways: on the one hand, they point to bottleneck problems of the astrocytic hypothesis; on the other hand, they show an incomplete database of modern biological science. In response to criticism O.G. Boyko suggested evolutionary study of the phenomenon of ageing combining the astrocytic hypothesis with the hypothesis of A. V. Makrushin. Such a combination, according to O.G. Boyko, rejects the criticism of A.A. Moskalev, who in turn met the emergence of a new doctrine of strong criticism, in particular, he writes: –
In general, A.A. Moskalev agrees with O.G. Boyko on what each evolutionary branch of live beings have inherent varying mechanisms of ageing, that is caused by the evolutionary design of phylogenetic group. In turn, with this point of view strongly disagree A.M. Olovnikov (the author of telomere-telomerase hypothesis of ageing), which in general repeated the arguments of A.A. Moskalev. A.M. Olovnikov assumes that ageing is performed in all species of Metazoa by the unknown molecular mechanism. In other words, that is not yet the discovered cellular mechanism.
Astrocytic hypothesis is discussed in reviews V.V. Zyuganov, Aubrey de Grey, A.V. Khalyavkin, A.I. Yashin, I. Yu. Popov, A. N. Ostrovsky, and V. N. Anisimov.
The first experimental confirmation
It is very likely that one of the postulate of the astrocytic hypothesis confirmed. Predicted hypothetical factor longevity of life in birds, that is physiological regeneration throughout the volume of nervous tissue (neurogenesis), really exists. (Unlike mammals, where this process takes place only in limited areas of the brain). Summarizing the overall database in 2009 year (results of different authors from 1980’s of the last century to this day) author of the astrocytic hypothesis concluded that physiological regeneration in birds takes place in the entire volume of nervous tissue without restrictions. Restored not only the loss in a pool of neurons, the brain of birds is capable to the reparative regeneration of traumatic injury that was the unknown at the time of nomination astrocytic hypothesis in 2000–2004 years. This phenomenon owes its existence because as expected, kept a well-developed radial embryonal network in brain of adult birds that provides migration of newborn neurons (neuroblasts) with a common to all vertebrates, their place of birth – ventral / subventricular zones of the brain into the place of reparations or their final localization in the brain of adult individuals.
Soon after the final wording of the astrocytic hypothesis in 2007 appeared incontrovertible data that neuronal turnover in brain of birds, although in a very small extent, but still limited – after selective removal of several cell types of neurons, they do not regenerate.
Predicted hypothetical factor of the longevity of life in birds, that is a permanent updated pool of neurons nervous tissue, in turn should prevent the accumulation senescent hormone–synthesizing neurons and thus must be hinder the development of Dilman process, i.e. parameters of homeostasis adult birds must be kept for life on one level.
In 2010 Vincent Julien Lecomte at least for wandering albatross (Diomedea exulans) established the fact that in this bird important physiological parameters (markers of ageing) of homeostasis for life do not change, as stipulated by the astrocytic hypothesis.
Almost is not limited, but still partial turnover of the neurons pool in the nervous tissue of birds require an irreplaceable part of the pool, which undergoes to cellular ageing, which is apparently tolerated into the organism level, probably because Diomedea exulans getting older: there are unfavourable changes with age in the ability to foraging and reproductive function.
However, this conclusion is true for other species of birds. It is GeneRally accepted that among birds there are no species with negligible ageing. This is true for mammals. However, the reparative potency of nervous tissue in birds with age, tend to decrease.
Value the astrocytic hypothesis with other hypothesis of ageing
In the PubMed database stored 164 567 articles devoted to the free-radical hypothesis of ageing, but they are very inconsistent. Therefore, this hypothesis has many supporters and opponents. The astrocytic hypothesis postulates a cascade of events and conditions under which, indeed, due to free-radical processes be can tear and wear of a multicellular organism. At least in mammals: – prohibition of physiological regeneration of nerve tissue (the neurons pool).
The elevation hypothesis of V.M. Dilman (modern version – the neuroendocrine theory of ageing) connects the ageing changes of organism with hypothalamic sensitivity to regulatory signals from the nervous system and endocrine glands with ageing at the organism level. The neuroendocrine theory is not yet completed, since the primary cause of age-endocrine changes in this theory is undisclosed. The astrocytic hypothesis describes the initial cause of these changes and its evolutionary origin. In addition, the astrocytic hypothesis associated with the hypothesis of ageing by G.P. Bidder and denies the majority postulates of the phenoptosis hypothesis by V. P. Skulachov. It should be noted that the biology of ageing is not generally accepted hypotheses. Assumed that schools support the postulates of their hypothesis of ageing. In aggregate, the hypothesis of ageing about 300.
Literature
References and notes
uk:Астроцитарна гіпотеза старіння ссавців