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Neuro-biological and Social Aspects of Advanced Age and the Role of Allostatic Load in Start and Maintenance of Processes of Ageing


Author: Minciună Vitalie
Degree:doctor habilitat of biology
Speciality: 03.00.13 - Human and animal physiology
Year:2008
Scientific consultants: Aurel Saulea
doctor habilitat, professor, State University of Medicine and Pharmacy "Nicolae Testemitanu"
Boris (decedat) Melnic
doctor habilitat, professor, Moldova State University
Institution:
Scientific council:

Status

The thesis was presented on the 26 August, 2008
Approved by NCAA on the 18 September, 2008

Abstract

Adobe PDF document0.50 Mb / in romanian

Thesis

CZU [612.816+612.746]-053.9

Adobe PDF document 4.20 Mb / in romanian
219 pages


Keywords

allostaic load, physiological tremor, biological signal transduction, β2-adrenoceptors, adenylate cyclase, primary, secondary and tertiary effects of allostasis, quality of life

Summary

In the course of time there grows the prevalence of diseases interpreted as secondary and tertiary effects of allostasis that testifies to increase allostatic load on the senior age stages of a life. The increase of allostatic load makes up simultaneously the consequence and the reason of decrease in the physical and mental compound health, defining the quality of a life.

The increase of allostatic load promotes activation, and then the infringement of the transmembrane transfers of the impulse, expressed in desensitization of membrane receptors. Decrease in sensitivity of receptors is found at many pathologies interpreted as tertiary effects of allostasis, defining parameters of diseases and death rate (cardiovascular diseases, a diabetes of the type II, obstructive diseases of lungs, pathological processes owing to decrease in immunity, etc.).

In the present research the transmembrane of transfer of an impulse was estimated at patients with expressed tertiary effects of allostasis - with hypertonic illness in conditions maximally resistant to antihypertensive therapies and within partial restoration of opportunities of antihypertensive corrections.

At the majority of patients with hypertonic illness homologus desensitization in lymphocytes β2-adrenoceptor has been revealed, expressed in decrease in affinity of receptors to agonists and increase of their density. At the same time we have found out, that it is not the unique form of infringement of transmembrane transfers during the increase of allostatic load. At some patients the characteristic of receptors did not differ practically from those at normotensive persons. The so-called "uncoupling" effect is shown at them when only the process of phosphorylation of separate components participating in transfers of an impulse takes place, owing to activation of AMPc-dependent process through stimulation of other types of receptors.

The change of allostatic load by carrying out the PGE2 rate with the purpose of pressure decrease and increase of sensitivity to antihypertensive drugs has revealed one more type of updating the transmembrane transfers of impulse - "down regulation", when the cell initially changes the number of receptors (by their interpolation in cytoplasmatic membrane), instead of their affinity to a hormone. At the same time the removal of receptors from a surface of an external membrane contributes to the increase of their affinity to the agonists that promotes restoration of physiological mechanisms of regulation of the transmembrane exchange processes and predetermines therapeutic effect.

In the present research the infringement of transmembrane transfers of impulse is, apparently, the reason of revealed infringement of synoptic transfer at elderly persons within the attempts of its activation by stimulation of a mechanical reflex and carrying out orthostatic tests. These changes make up the consequence of increase, in the long run, of basal activity of the impellent centers and long activation of biochemical processes at the level of postsynaptic membrane that leads to the infringement of processes of phosphorylation/dephosphorylation of components participating in transfers of an impulse and maintenance of receptors in a condition of low affinity to neuromediators. In its turn the infringement of synoptic transfer promotes delay of reactance of the central nervous system, infringement of processes of excitation and braking and represents the reason of decrease in adaptive opportunities of an organism to constantly changing conditions of an environment.

Thus, the increase of allostatic load in the long run and the infringement of the transmembrane transfers of impulse as such refer to the basic processes influencing life expectancy and process of ageing.

Summary