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Protein aggregation as an element of aging



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E learning in pharmaceutical continuing

Protein aggregation as an element of aging 
process 
Protein aggregation is one of the common characteristics of 
aging. It is a consequence of abnormalities of protein structure 
induced by destructive actions (free radicals, mechanical impact, 
temperature) but also by abnormalities of synthesis, mainly due 
to mutation. The cell defends itself by destroying abnormally 
structured proteins, determining short life span for unstable 
proteins, altering the rate of synthesis and the rate of protein 
elimination. Metabolism gradually slows down with aging and 
the amount of abnormally structured proteins increases which 
in consequence accelerates the rate of aggregation [34, 35]. 
A constellation of pathological processes that ensue are natural 
companions of aging.
Discussion
The mechanism that determines red blood cell death is eryth-
rocyte speciic and underlies the universal character of dying 
in nature. As a consequence, the deinition of life appears to 
refer to automation that provides biological structures with the 
features of life, but belonging to the living world is determined 
by the programmed duration of functioning terminated by death.
A living thing is then a form of animated nature, which has 
the features of independence as a result of automation and pos-
sesses its own compatible with nature program of action which 
is time-limited beforehand.
In accordance with this deinition living things are those 
natural creatures which form the integral part of nature promot-
ing its development. It means that Nature creates things deined 
as living providing them with the features of independence and 
simultaneously limiting their time of function. Only combined 
conditions determine the consistency with animated nature and 
provide a basis for interpreting the forms of nature as living. In 
this sense immortal cells are not consistent with nature, and they 
may be regarded as automatic structures similar to man-made 
robots. In turn, viruses lacking independence may correspond 
to cell destroying venoms and toxins.
Among the characteristics of living things one feature appears 
universal and it is the presence of clock mechanisms. An oscilla
-
tor is a system that includes a negative feedback loop, which is 
coupled with a positive feedback loop to obtain appropriate signal 
characteristics [7, 36]. They usually involve a speciic process 
serving as the basis of time but as a result of cooperation they 
cover much wider range of functions.The universality of variable 
frequency oscillators, which are encountered in almost all cells 
(including bacterial cells), appears to emphasize the real need 
for self-sustained rhythmic activity. The frequency of oscillations 
ranges from one cycle per second to one cycle per day or even 
per year. Humans have circadian rhythms coordinated by one 
master clock being superior to peripheral oscillators. The circadian 
rhythm in humans developed in line with the evolution of life on 
Earth in the light-dark cycle. The role of the circadian rhythm 
may be to anticipate changes in individual activity related to the 
onset of daylight. For this reason the master clock in humans (the 
suprachiasmatic nucleus - SCN) is linked to the retina through 
neuronal communication [6].
Variable frequency oscillators in cells (regulation of glyco-
lytic enzyme activity, changes in the concentration of calcium 
ions and others) perform a different function. They include 
a regulatory feedback loop between DNA and protein. The 
function of the master clock in humans is regulated by cyclic 
changes in the activity of the transcription factors CLOCK and 
BMAL-1 acting as transcriptional repressor (upon Per and 
Cry proteins).
The role of this phenomenon is not clear yet. Evidence shows 
that there is a relationship between the presence of oscillators and 
various individual processes in the cell. However, the universality 
of this phenomenon may imply its general and fundamental role 
of maintaining an active form of life processes, which being auto-
matically controlled have a natural tendency toward minimizing 
their activity upon reaching the programmed level.
Further studies are warranted to answer the question whether 
the presence of oscillators is a characteristic feature and a pre-
requisite for life and whether it may be considered as one of 
its criteria.
References
1. Jagers op Akkerhuis G.A.J.M. (2010): Towards a hierarchi
-
cal deinition of life, the organism, and death. Found Sci. 
15, pp. 245–262. 
2. Cleland C.E., Chyba C.F. (2002): Deining ‘life’. Origins Life 
Evol. Biosph. 32, pp. 387–393.
3. McKay C.P. (2004): What is life – and how do we search for 
it in other worlds. PLoSBiol 2, pp. 1260–1264.
4. Joyce G.F. (1988), forward, in: D.W. Deamer, G.R. Fleis
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chaker (eds.): Origins of life: the Central Concepts. Jones 
& Barlett, Boston, pp. xi-xii.
5. Korzeniewski B. (2001): Cybernetic formulation of the dei
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nition of life. J. Theoretical Biology 209, pp. 275-286.
6. Gánti T (1986): Podstawy życia. PW “Wiedza powszech
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na”, Warszawa.
7. Reppert S.M., Weaver D.R. (2002): Coordinating of circa
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dian timing in mammals. Nature 418, pp. 935–941.
8. van Gelder R.N., Herzog E.D., Schwartz W.J., Taghert P.H. 
(2003): Circadian rhythms: in the loop at last. Science 300, 
pp. 1534-1535.
9. Pasini E.M., Kirkegaard M, Mortensen P., Lutz H.U., Thom
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as A.W, Mann M. (2006): In-depth analysis of the mem
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brane and cytosolic proteome of red blood cells. Blood 108, 
pp. 791-801.
10. Goodman S.R., Kurdia A., Ammann L., Kakhniashvili D., 
Daescu O. (2007): The human red blood cell proteome and 
interactome. ExpBiol Med 232, pp. 1391-1408.
11. Lichtman M., Beutler E., Kaushansky K., Kipps T., 
Seligsohn U., Prchal J.T. (2006): Williams: Hematology. 7th 
ed. McGraw-Hill New York, Chicago, San Francisco, Lis
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