Yuru Denesenko - Academia.edu (original) (raw)

Papers by Yuru Denesenko

Research paper thumbnail of Simulation of drosophila aging in silico

Advances in Gerontology, 2011

of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging ... more of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging from epiphenomenona accompanying them. The modern methods of simulation modeling may be the proper tool for correct isolation. The point of their application is reproduction of external aging manifesta tions in silico, and, in the first place, of standard survival curves with the help of the simplest internal mech anism. It seems that such a mechanism will be prime mover of aging. The aging model of one the most popular objects of experimental biology⎯a fruit fly(Drosophila melanogaster) created by us (http://winmo bile.biz/moton/moto.html), is based on the assumption that the key mechanism of aging is cellularity loss, the speed of which is determined by the parameters of active oxygen forms generation in motoneurons.

Research paper thumbnail of Cellularity loss and dilman’s problem: An in silico study

Biochemistry (Moscow), 2012

We assume that prolonged trends of increasing concentration of hormones could be a consequence of... more We assume that prolonged trends of increasing concentration of hormones could be a consequence of deterioration of functioning of glands producing inhibitors of their synthesis. Such deterioration would result from loss of cellularity of the glands. Experiments in silico carried out using the model at http://www.winmobile.biz/monstr/ show that, in principle, the diversity of hormonal effects that accompany phenoptosis of multicellular organisms can be provided with a simple "software mechanism". This mechanism is based on the gradual loss of cellularity as a result of continuous run of apoptosis in some cells of the glands due to natural fluctuations in levels of intracellular inducers of apoptosis. The main practical sense of our work lies in the illustration of the fact that substances inhibiting cellularity loss can theoretically be effective suppressors of hormonal changes characteristic for aging.

Research paper thumbnail of Aging saves populations from extinction under lack of resources: in silico experiments

Biochemistry (Moscow), 2015

By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question... more By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question as to what advantages it gives to communities containing elderly and naturally weakened individuals. We believe that the broadest prevalence of the aging phenomenon is accounted for, particularly, by the fact that in certain situations occurrence of elderly individuals may guarantee not only evolution, but also the mere existence of populations. The goal of our study was to create a mathematical model illustrating the occurrence of situations when existence of elderly individuals accounts for population survival, whereas an ageless population would be completely extinguished. A logic basis for such model is as follows: 1) natural populations exist under conditions of uneven renewal of resources; 2) if resources are renewed at a high level and rapidly compensated by their restoration, then a population strives to achieve a maximum size, which is limited not by resource availability, but specific biological mechanisms; 3) rate of resource influx may decline down to zero very rapidly (e.g. during drought); 4) a capacity, at least, for some individuals to survive during resource shortage is crucial for survival of the entire population; 5) rapid extinction of the weaker elderly individuals saves resources for survival of the younger and stronger ones. A multi-agent simulation is used as a mathematical basis for the proposed model (http://www.winmobile.biz). In silico experiments confirmed the lack of fatal contradictions in our logical construction. The presence of the aged individuals once the aging program has been turned at the age of 25-30 years results in a 24-26% increase in lifetime of the population.

Research paper thumbnail of Age-related cellularity loss in silico

Russian Journal of General Chemistry, 2010

Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of th... more Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of the most reliable mechanisms realizing the program of aging. A signal starting the program of cellular death (PCD) in a part of cellular population can be an excess of a threshold level of PCD inductor production as a result of stochastic processes. Speed of aging is regulated by the proportion of average PCD inductor production, variability of this rate and the size of a threshold level of the PCD induction. The developed model allows to study the progress of these processes and their modulation by antioxidants in silico.

Research paper thumbnail of Aging Saves Populations from Extinction under Lack of Resources: in silico Experiments

—By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a questio... more —By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question as to what advantages it gives to communities containing elderly and naturally weakened individuals. We believe that the broadest prevalence of the aging phenomenon is accounted for, particularly, by the fact that in certain situations occurrence of elderly individuals may guarantee not only evolution, but also the mere existence of populations. The goal of our study was to create a mathematical model illustrating the occurrence of situations when existence of elderly individuals accounts for population survival, whereas an ageless population would be completely extinguished. A logic basis for such model is as follows: 1) natural populations exist under conditions of uneven renewal of resources; 2) if resources are renewed at a high level and rapidly compensated by their restoration, then a population strives to achieve a maximum size, which is limited not by resource availability, but specific biological mechanisms; 3) rate of resource influx may decline down to zero very rapidly (e.g. during drought); 4) a capacity, at least, for some individuals to survive during resource shortage is crucial for survival of the entire population; 5) rapid extinction of the weaker elderly individuals saves resources for survival of the younger and stronger ones. A multi-agent simulation is used as a mathematical basis for the proposed model (http://homebear.ru/en/download.php). In silico experiments confirmed the lack of fatal contradictions in our logical construction. When the aging program is enabled at age of 25-30 years, it results in increasing population survival by 24-26%. The assumption that in animals aging represented as a slow phenoptosis is a process characterized by decreased viability controlled by a special genetic program turned out to be highly fruitful, primarily, for practical

Research paper thumbnail of CELLULARITY LOSS AND THE DILMAN'S PROBLEM: IN SILICO RESEARCH

We assumed that prolonged trends of hormone concentration increase can be a consequence of deteri... more We assumed that prolonged trends of hormone concentration increase can be a consequence of deteriorating func"
tioning of glands producing inhibitors of synthesis. This deterioration results from cellularity loss of the glands. The
experiments in silico carried out with the model http://www.winmobile.biz/monstr/ help prove that the phenomenon
of loss of sensitivity to hormonal signals with subsequent stop of cycles can be imitated in the elementary modeling
system, and the basis of the given phenomenon, as well as in the basis of the majority of gerontological phenomena,
can lie in cellularity loss. The experiments in silico show that, in principle, the diversity of hormonal effects that
accompany of the phenoptosis of multicellular organisms can be provided by a simple “software mechanism” This
mechanism based on the gradual loss of cellularity as a result of continuous run of apoptosis in some cells of the glands
due to natural fluctuations in levels of intracellular inducers of apoptosis. The main practical meaning of our work lies
in the illustration of the fact that substances inhibiting cellularity loss can theoretically be effective suppressors of hor"
monal changes characteristic for aging.
Key words: phenoptosis, apoptosis, aging, imitation modeling, cellularity loss, hormones, elevation theory

Research paper thumbnail of Simulation of Drosophila aging in silico

One of the main tasks of modern gerontology is isolation of a group of phenomena essential for ag... more One of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging from epiphenomenona accompanying them. The modern methods of simulation modeling may be the proper tool for correct isolation. The point of their application is reproduction of external aging manifestations in silico, and, in the first place, of standard survival curves with the help of the simplest internal mechanism. It seems that such a mechanism will be prime mover of aging. The aging model of one the most popular objects of experimental biology-a fruit fly (Drosophila melanogaster) created by us (http://homebear.ru/en/download.php) , is based on the assumption that the key mechanism of aging is cellularity loss, the speed of which is determined by the parameters of active oxygen forms generation in motoneurons. Aging is an amazing phenomenon and in the course of biology development scientists get more and more interested in studying it. The most intriguing question of this field of knowledge can be formulated as follows: what mechanism provides gradual decrease in viability of a multicellular organism? Development of experimental biology methods aroused a desire to answer it, studying the molecular changes which accompany the aging process. Researchers have revealed many such changes starting from lipofuscin accumulation to telomere shortening [1]. Moreover, the system of mechanisms of the somatic cells programmed death was discovered and its participation in "self-destruction" of the whole organism was proved by the number of observations [5, 14]. The success in the search of processes characteristics of which correlate with age also had a reverse side. A lot of aging theories exaggerating the value of some or another molecular change have sprung up. Redundancy of the existing aging hypotheses pool is evident to the majority of authors trying to analyze the state of things in gerontology [1]. A multicellular organism is a multilevel self-organizing system. Activity of its elements is coordinated by the most complicated network of feedbacks. Any action is accompanied by a loop of gene expression changes, synthesis of hormones, immune and electrophysiological reactions, etc. The majority of them influences fitness. Nevertheless, for understanding of the processes taking place, for example, at digestion of food it is enough to keep in mind not more than ten physiological and biochemical reactions. The dialectics of the cognitive process is such that abstraction from the majority of details allows creating conceptual models which become a basis of the further detailed elaboration, but already without any loss of understanding of the essence of the phenomenon studied. The theorist who is searching for the main laws of biological processes can achieve success only referring the majority of reactions accompanying them to epiphenomena. Distinguishing the group of phenomena essential for aging from epiphenomena accompanying them is one of the main tasks of modern gerontology. We believe that modern methods of mathematical modeling can be the tool for distinguishing them properly. The sense of their application is reproduction of the "external" aging manifestations in silico, first of all of the standard survivor curves , by means of the simplest «internal mechanism». This mechanism will apparently be the most essential aging mover. Naturally "the internal mechanism» modeling should be based on the biological facts without contradicting them. Creating the aging model of one of the most popular experimental biology objects – a fruit fly (Drosophila melanogaster) based on the simplest presuppositions possible was the task of this research. Drosophila melanogaster life expectancy is measured by several weeks. This organism is an insect with complete metamorphosis. All somatic cells of an imago are postmitotic. Nevertheless, drosophila «survivor curves» have the S-shape characteristic for the majority of animals [8, 12]. Aging modeling of the given object is essentially facilitated by the fact that cells responsible for this process are identified reliably enough and that the key role of the free-radical processes in aging [12] is clearly demonstrated. As it is known, the basic source of reactive oxygen species in eukaryotic cells is a respiratory chain of mitochondria. One of the main enzymesantioxidants is superoxide dismutase (SOD), catalyzing superoxide anion transformation into hydro peroxide and oxygen. It is known that the drosophilae, incapable of SOD synthesis are characterized by short life expectancy [16]. In the early nineties of the last century scientists succeeded in breeding drosophila, having appreciable quantities of human SOD, however, their life expectancy practically didn't differ from that of the wild type. Then the technique appeared that allowed to "switch on" SOD expression only in the necessary tissues by means of additional genetic construction. Specific expression of this gene in motoneurons turned out to make life expectancy longer. Moreover, human SOD introduction into motoneurons only returned life expectancy characteristic for the wild type to the flies defective in this enzyme. Motoneurons are convenient for modeling because of the fact that their quantity in one fly is defined precisely enough and is about 80 [11]. It is possible to assume that the natural death of a drosophila occurs due to the motoneurons number decrease to a critical level. The model of cellularity loss of a homogeneous population of postmitotic cells described http://homebear.ru/en/download.php, in our work [7] has served as the basis for creation of the drosophila aging model. Its logical bases are as follows: • Postmitotic cells are capable to generate a number of substances provoking programmed cellular death (PCD)-for example, hydrogen peroxide. Let us call X the total concentration of such apoptosis signals. • At the increase of X quantity up to a certain limit produced during a time interval which can be named a «cycle»(in this particular case the length of one cycle is 24 hours), the mechanism of self-liquidation works • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are weakly interdependent, they will be distributed according to the normal law (Gaussian law). The presence of an asymmetry and an excess at the X distribution does not change the analyzed laws essentially. The main thing is that the function of X

Research paper thumbnail of Age-related cellularity loss in silico

Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be on... more Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of the most reliable mechanisms realizing the program of ageing. A signal starting the program of cellular death (PCD) in a part of cellular population can be an excess of a threshold level of PCD inductor production as a result of stochastic processes. Speed of ageing is regulated by the proportion of average PCD inductor production, variability of this rate and the size of a threshold level of the PCD induction. The developed model allows to study the progress of these processes and their modulation by antioxidants in silico. The simultaneous coexistence a number of contradicting theories of ageing reflects system crisis of modern gerentology. One of the approaches making the construction of the unified theory of ageing easier, can be formation of some basic methodological framework based on obvious premises the majority of biologists accept. Because of the complexity of this problem (that is determined by complexity of the described phenomena) it is possible to suggest to solve partially, considering successively separate sides of the phenomenon of ageing in hope that this activity will facilitate the future synthesis. This work represents the attempt of realization of such approach as applied to to the phenomenon of cellularity loss in postmitotic tissues. Reduction of the number of cells composing tissues and bodies, seems to be one of the simplest and therefore reliable mechanisms of progressing with the years reducing resiliency of a multicellular organism. Importance of this process for ageing mammals is well enough shown [1, 2, 3, 4]. It is also obvious, that ageing of imago of diptera, submitting to the same statistical regularities, as ageing of the majority of other animals, is caused mainly by postmititic tissues ageing [5, 6]. By now enough facts are accumulated for construction of model of age cellularity loss, allowing to take into account delay of this process by geroprotectors. The preconditions of its logic are as follows: • Postmitotic cells are capable to generate the substances provoking programmed cellular death (PCD) [7],-for example, hydrogen peroxide. We shall consider certain substance X (we would not like to concretize its nature up to the description of work of the mechanism of cellularity loss in general). • At the increase of X quantity up to a certain limit produced during a time interval which can be named "cycle", the mechanism of self-liquidation works. • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are mutually weakly dependent, their distribution will submit to the normal law (Gaussian law). As it will be visible from the further statement, presence of asymmetry and excess at distribution of X size does not change analyzed laws essentially. The main thing is that function of distribution X at convergence of argument to infinity asymptotically tends to zero. As such curve does not cross the X-axis, there can be arbitrary large deviationsfrom average X size. • In a cellular population, at an average level of X production that is lower than the threshold, there will be cells producing the amount of X which will exceed «the threshold of self-liquidation». Let's take Uα size (fig. 1.) as the threshold X size at the excess of which the mechanism of self-liquidation is started. Then 1-α (α-the area of light zone) will be equal to the proportion of cells dying during a cycle (as Gaussian curve in figure is normalized, the whole area under it is equal to 1). Shifting size Uα and/or changing σ (the standard deviation from X sizes distribution X size, for the normalized distribution σ = 1), experimenters or evolving alive systems receive an opportunity to adjust speed of cellularity loss, and, hence, the speed of ageing. Even the superficial visual analysis (fig. 1) convinces that insignificant shifts of Uα can cause big changes 1-α or, concretizing the biological sense of considered processes, it is possible to assume that weak repeating influences, constant introduction of small geroprotector dozes for example, are capable to cause significant delay of ageing. Fig. 1. The normalized curve of normal distribution. Methods For quantitative confirmation of the concept stated above the simulated multi-agent model with use of the approaches stated in work [8] was

Research paper thumbnail of CELLULARITY LOSS AND THE DILMAN'S PROBLEM: IN SILICO RESEARCH

We assumed that prolonged trends of hormones concentration increase can be a consequence of funct... more We assumed that prolonged trends of hormones concentration increase can be a consequence of functioning deterioration of glands producing inhibitors of synthesis.
This deterioration results from glands cellularity loss. The experiments in silico carried out with the help of model http://homebear.ru/en/download.php prove that the phenomenon of loss of sensitivity to hormonal signals with the subsequent stop of cycles can be imitated in the elementary modelling system, and in the basis of the given phenomenon, as well as in the basis of the majority of
gerontological phenomena, cellularity loss can lie. The experiments in silico show that, in principle, the diversity of hormonal effects that accompany the realization of the phenoptosis of multicellular organisms can be provided with a simple “software mechanism” This mechanism based on the gradual loss of cellularity as a result of continuous run of apoptosis in some cells of the glands due to natural fluctuations in levels of intracellular inducers of apoptosis. The main practical sense of our work lies in the illustration of the fact that substances inhibiting cellularity loss can theoretically be effective suppressors of hormonal changes characteristic for aging.

Research paper thumbnail of Aging Saves Populations from Extinction under Lack of Resources: in silico

By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question... more By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question as to what advantages it gives to communities containing elderly and naturally weakened individuals. We believe that the broadest prevalence of the aging phenomenon is accounted for, particularly, by the fact that in certain situations occurrence of elderly individuals may guarantee not only evolution, but also the mere existence of populations. The goal of our study was to create a mathematical model illustrating the occurrence of situations when existence of elderly individuals accounts for population survival, whereas an ageless population would be completely extinguished. A logic basis for such model is as follows: 1) natural populations exist under conditions of uneven renewal of resources; 2) if resources are renewed at a high level and rapidly compensated by their restoration, then a population strives to achieve a maximum size, which is limited not by resource availability, but specific biological mechanisms; 3) rate of resource influx may decline down to zero very rapidly (e.g. during drought); 4) a capacity, at least, for some individuals to survive during resource shortage is crucial for survival of the entire population; 5) rapid extinction of the weaker elderly individuals saves resources for survival of the younger and stronger ones. A multi-agent simulation is used as a mathematical basis for the proposed model (http://www.winmobile.biz). In silico experiments confirmed the lack of fatal contradictions in our logical construction. When the aging program is enabled at age of 25-30 years, it results in increasing population survival by 24-26%. The assumption that in animals aging represented as a slow phenoptosis is a process characterized by decreased viability controlled by a special genetic program turned out to be highly fruitful, primarily, for practical gerontology [1]. A search for the aging program ―switch-off‖ resulted in emerging of a number of promising drugs. Among them, the most effective drug can be used for treatment of a broad range of age-related pathologies,

Research paper thumbnail of Stat1 en

Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be on... more Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of the most reliable mechanisms realizing the program of ageing. A signal starting the program of cellular death (PCD) in a part of cellular population can be an excess of a threshold level of PCD inductor production as a result of stochastic processes. Speed of ageing is regulated by the proportion of average PCD inductor production, variability of this rate and the size of a threshold level of the PCD induction. The developed model allows to study the progress of these processes and their modulation by antioxidants in silico. The simultaneous coexistence a number of contradicting theories of ageing reflects system crisis of modern gerentology. One of the approaches making the construction of the unified theory of ageing easier, can be formation of some basic methodological framework based on obvious premises the majority of biologists accept. Because of the complexity of this problem (that is determined by complexity of the described phenomena) it is possible to suggest to solve partially, considering successively separate sides of the phenomenon of ageing in hope that this activity will facilitate the future synthesis. This work represents the attempt of realization of such approach as applied to to the phenomenon of cellularity loss in postmitotic tissues. Reduction of the number of cells composing tissues and bodies, seems to be one of the simplest and therefore reliable mechanisms of progressing with the years reducing resiliency of a multicellular organism. Importance of this process for ageing mammals is well enough shown [1, 2, 3, 4]. It is also obvious, that ageing of imago of diptera, submitting to the same statistical regularities, as ageing of the majority of other animals, is caused mainly by postmititic tissues ageing [5, 6]. By now enough facts are accumulated for construction of model of age cellularity loss, allowing to take into account delay of this process by geroprotectors. The preconditions of its logic are as follows: • Postmitotic cells are capable to generate the substances provoking programmed cellular death (PCD) [7],-for example, hydrogen peroxide. We shall consider certain substance X (we would not like to concretize its nature up to the description of work of the mechanism of cellularity loss in general). • At the increase of X quantity up to a certain limit produced during a time interval which can be named "cycle", the mechanism of self-liquidation works. • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are mutually weakly dependent, their distribution will submit to the normal law (Gaussian law). As it will be visible from the further statement, presence of asymmetry and excess at distribution of X size does not change analyzed laws essentially. The main thing is that function of distribution X at convergence of argument to infinity asymptotically tends to zero. As such curve does not cross the X-axis, there can be arbitrary large deviationsfrom average X size. • In a cellular population, at an average level of X production that is lower than the threshold, there will be cells producing the amount of X which will exceed «the threshold of self-liquidation». Let's take Uα size (fig. 1.) as the threshold X size at the excess of which the mechanism of self-liquidation is started. Then 1-α (α-the area of light zone) will be equal to the proportion of cells dying during a cycle (as Gaussian curve in figure is normalized, the whole area under it is equal to 1). Shifting size Uα and/or changing σ (the standard deviation from X sizes distribution X size, for the normalized distribution σ = 1), experimenters or evolving alive systems receive an opportunity to adjust speed of cellularity loss, and, hence, the speed of ageing. Even the superficial visual analysis (fig. 1) convinces that insignificant shifts of Uα can cause big changes 1-α or, concretizing the biological sense of considered processes, it is possible to assume that weak repeating influences, constant introduction of small geroprotector dozes for example, are capable to cause significant delay of ageing. Fig. 1. The normalized curve of normal distribution. Methods For quantitative confirmation of the concept stated above the simulated multi-agent model with use of the approaches stated in work [8] was

Research paper thumbnail of Simulation of Drosophila aging in silico

One of the main tasks of modern gerontology is isolation of a group of phenomena essential for ag... more One of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging from epiphenomenona accompanying them. The modern methods of simulation modeling may be the proper tool for correct isolation. The point of their application is reproduction of external aging manifestations in silico, and, in the first place, of standard survival curves with the help of the simplest internal mechanism. It seems that such a mechanism will be prime mover of aging. The aging model of one the most popular objects of experimental biology-a fruit fly (Drosophila melanogaster) created by us (http://winmobile.biz/moton/en/moto.html) , is based on the assumption that the key mechanism of aging is cellularity loss, the speed of which is determined by the parameters of active oxygen forms generation in motoneurons. Aging is an amazing phenomenon and in the course of biology development scientists get more and more interested in studying it. The most intriguing question of this field of knowledge can be formulated as follows: what mechanism provides gradual decrease in viability of a multicellular organism? Development of experimental biology methods aroused a desire to answer it, studying the molecular changes which accompany the aging process. Researchers have revealed many such changes starting from lipofuscin accumulation to telomere shortening [1]. Moreover, the system of mechanisms of the somatic cells programmed death was discovered and its participation in "self-destruction" of the whole organism was proved by the number of observations [5, 14]. The success in the search of processes characteristics of which correlate with age also had a reverse side. A lot of aging theories exaggerating the value of some or another molecular change have sprung up. Redundancy of the existing aging hypotheses pool is evident to the majority of authors trying to analyze the state of things in gerontology [1]. A multicellular organism is a multilevel self-organizing system. Activity of its elements is coordinated by the most complicated network of feedbacks. Any action is accompanied by a loop of gene expression changes, synthesis of hormones, immune and electrophysiological reactions, etc. The majority of them influences fitness. Nevertheless, for understanding of the processes taking place, for example, at digestion of food it is enough to keep in mind not more than ten physiological and biochemical reactions. The dialectics of the cognitive process is such that abstraction from the majority of details allows creating conceptual models which become a basis of the further detailed elaboration, but already without any loss of understanding of the essence of the phenomenon studied. The theorist who is searching for the main laws of biological processes can achieve success only referring the majority of reactions accompanying them to epiphenomena. Distinguishing the group of phenomena essential for aging from epiphenomena accompanying them is one of the main tasks of modern gerontology. We believe that modern methods of mathematical modeling can be the tool for distinguishing them properly. The sense of their application is reproduction of the "external" aging manifestations in silico, first of all of the standard survivor curves , by means of the simplest «internal mechanism». This mechanism will apparently be the most essential aging mover. Naturally "the internal mechanism» modeling should be based on the biological facts without contradicting them. Creating the aging model of one of the most popular experimental biology objects – a fruit fly (Drosophila melanogaster) based on the simplest presuppositions possible was the task of this research. Drosophila melanogaster life expectancy is measured by several weeks. This organism is an insect with complete metamorphosis. All somatic cells of an imago are postmitotic. Nevertheless, drosophila «survivor curves» have the S-shape characteristic for the majority of animals [8, 12]. Aging modeling of the given object is essentially facilitated by the fact that cells responsible for this process are identified reliably enough and that the key role of the free-radical processes in aging [12] is clearly demonstrated. As it is known, the basic source of reactive oxygen species in eukaryotic cells is a respiratory chain of mitochondria. One of the main enzymes-antioxidants is superoxide dismutase (SOD), catalyzing superoxide anion transformation into hydro peroxide and oxygen. It is known that the drosophilae, incapable of SOD synthesis are characterized by short life expectancy [16]. In the early nineties of the last century scientists succeeded in breeding drosophila, having appreciable quantities of human SOD, however, their life expectancy practically didn't differ from that of the wild type. Then the technique appeared that allowed to "switch on" SOD expression only in the necessary tissues by means of additional genetic construction. Specific expression of this gene in motoneurons turned out to make life expectancy longer. Moreover, human SOD introduction into motoneurons only returned life expectancy characteristic for the wild type to the flies defective in this enzyme. Motoneurons are convenient for modeling because of the fact that their quantity in one fly is defined precisely enough and is about 80 [11]. It is possible to assume that the natural death of a drosophila occurs due to the motoneurons number decrease to a critical level. The model of cellularity loss of a homogeneous population of postmitotic cells describedhttp://www.winmobile.biz/shou/en/demoApp.php, in our work [7] has served as the basis for creation of the drosophila aging model. Its logical bases are as follows: • Postmitotic cells are capable to generate a number of substances provoking programmed cellular death (PCD)-for example, hydrogen peroxide. Let us call X the total concentration of such apoptosis signals. • At the increase of X quantity up to a certain limit produced during a time interval which can be named a «cycle»(in this particular case the length of one cycle is 24 hours), the mechanism of self-liquidation works • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are weakly interdependent, they will be distributed according to the normal law (Gaussian law). The presence of an asymmetry and an excess at the X distribution does not change the analyzed laws essentially. The main thing is that the function of X distribution at convergence of argument to infinity asymptotically approaches zero. As this curve does not cross the X-axis, there can be arbitrary large deviations from average X size. • In a cellular population, at an average level of X production that is lower than the threshold, there will be cells producing the amount of X which will

Research paper thumbnail of Simulation of drosophila aging in silico

Advances in Gerontology, 2011

of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging ... more of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging from epiphenomenona accompanying them. The modern methods of simulation modeling may be the proper tool for correct isolation. The point of their application is reproduction of external aging manifesta tions in silico, and, in the first place, of standard survival curves with the help of the simplest internal mech anism. It seems that such a mechanism will be prime mover of aging. The aging model of one the most popular objects of experimental biology⎯a fruit fly(Drosophila melanogaster) created by us (http://winmo bile.biz/moton/moto.html), is based on the assumption that the key mechanism of aging is cellularity loss, the speed of which is determined by the parameters of active oxygen forms generation in motoneurons.

Research paper thumbnail of Cellularity loss and dilman’s problem: An in silico study

Biochemistry (Moscow), 2012

We assume that prolonged trends of increasing concentration of hormones could be a consequence of... more We assume that prolonged trends of increasing concentration of hormones could be a consequence of deterioration of functioning of glands producing inhibitors of their synthesis. Such deterioration would result from loss of cellularity of the glands. Experiments in silico carried out using the model at http://www.winmobile.biz/monstr/ show that, in principle, the diversity of hormonal effects that accompany phenoptosis of multicellular organisms can be provided with a simple "software mechanism". This mechanism is based on the gradual loss of cellularity as a result of continuous run of apoptosis in some cells of the glands due to natural fluctuations in levels of intracellular inducers of apoptosis. The main practical sense of our work lies in the illustration of the fact that substances inhibiting cellularity loss can theoretically be effective suppressors of hormonal changes characteristic for aging.

Research paper thumbnail of Aging saves populations from extinction under lack of resources: in silico experiments

Biochemistry (Moscow), 2015

By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question... more By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question as to what advantages it gives to communities containing elderly and naturally weakened individuals. We believe that the broadest prevalence of the aging phenomenon is accounted for, particularly, by the fact that in certain situations occurrence of elderly individuals may guarantee not only evolution, but also the mere existence of populations. The goal of our study was to create a mathematical model illustrating the occurrence of situations when existence of elderly individuals accounts for population survival, whereas an ageless population would be completely extinguished. A logic basis for such model is as follows: 1) natural populations exist under conditions of uneven renewal of resources; 2) if resources are renewed at a high level and rapidly compensated by their restoration, then a population strives to achieve a maximum size, which is limited not by resource availability, but specific biological mechanisms; 3) rate of resource influx may decline down to zero very rapidly (e.g. during drought); 4) a capacity, at least, for some individuals to survive during resource shortage is crucial for survival of the entire population; 5) rapid extinction of the weaker elderly individuals saves resources for survival of the younger and stronger ones. A multi-agent simulation is used as a mathematical basis for the proposed model (http://www.winmobile.biz). In silico experiments confirmed the lack of fatal contradictions in our logical construction. The presence of the aged individuals once the aging program has been turned at the age of 25-30 years results in a 24-26% increase in lifetime of the population.

Research paper thumbnail of Age-related cellularity loss in silico

Russian Journal of General Chemistry, 2010

Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of th... more Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of the most reliable mechanisms realizing the program of aging. A signal starting the program of cellular death (PCD) in a part of cellular population can be an excess of a threshold level of PCD inductor production as a result of stochastic processes. Speed of aging is regulated by the proportion of average PCD inductor production, variability of this rate and the size of a threshold level of the PCD induction. The developed model allows to study the progress of these processes and their modulation by antioxidants in silico.

Research paper thumbnail of Aging Saves Populations from Extinction under Lack of Resources: in silico Experiments

—By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a questio... more —By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question as to what advantages it gives to communities containing elderly and naturally weakened individuals. We believe that the broadest prevalence of the aging phenomenon is accounted for, particularly, by the fact that in certain situations occurrence of elderly individuals may guarantee not only evolution, but also the mere existence of populations. The goal of our study was to create a mathematical model illustrating the occurrence of situations when existence of elderly individuals accounts for population survival, whereas an ageless population would be completely extinguished. A logic basis for such model is as follows: 1) natural populations exist under conditions of uneven renewal of resources; 2) if resources are renewed at a high level and rapidly compensated by their restoration, then a population strives to achieve a maximum size, which is limited not by resource availability, but specific biological mechanisms; 3) rate of resource influx may decline down to zero very rapidly (e.g. during drought); 4) a capacity, at least, for some individuals to survive during resource shortage is crucial for survival of the entire population; 5) rapid extinction of the weaker elderly individuals saves resources for survival of the younger and stronger ones. A multi-agent simulation is used as a mathematical basis for the proposed model (http://homebear.ru/en/download.php). In silico experiments confirmed the lack of fatal contradictions in our logical construction. When the aging program is enabled at age of 25-30 years, it results in increasing population survival by 24-26%. The assumption that in animals aging represented as a slow phenoptosis is a process characterized by decreased viability controlled by a special genetic program turned out to be highly fruitful, primarily, for practical

Research paper thumbnail of CELLULARITY LOSS AND THE DILMAN'S PROBLEM: IN SILICO RESEARCH

We assumed that prolonged trends of hormone concentration increase can be a consequence of deteri... more We assumed that prolonged trends of hormone concentration increase can be a consequence of deteriorating func"
tioning of glands producing inhibitors of synthesis. This deterioration results from cellularity loss of the glands. The
experiments in silico carried out with the model http://www.winmobile.biz/monstr/ help prove that the phenomenon
of loss of sensitivity to hormonal signals with subsequent stop of cycles can be imitated in the elementary modeling
system, and the basis of the given phenomenon, as well as in the basis of the majority of gerontological phenomena,
can lie in cellularity loss. The experiments in silico show that, in principle, the diversity of hormonal effects that
accompany of the phenoptosis of multicellular organisms can be provided by a simple “software mechanism” This
mechanism based on the gradual loss of cellularity as a result of continuous run of apoptosis in some cells of the glands
due to natural fluctuations in levels of intracellular inducers of apoptosis. The main practical meaning of our work lies
in the illustration of the fact that substances inhibiting cellularity loss can theoretically be effective suppressors of hor"
monal changes characteristic for aging.
Key words: phenoptosis, apoptosis, aging, imitation modeling, cellularity loss, hormones, elevation theory

Research paper thumbnail of Simulation of Drosophila aging in silico

One of the main tasks of modern gerontology is isolation of a group of phenomena essential for ag... more One of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging from epiphenomenona accompanying them. The modern methods of simulation modeling may be the proper tool for correct isolation. The point of their application is reproduction of external aging manifestations in silico, and, in the first place, of standard survival curves with the help of the simplest internal mechanism. It seems that such a mechanism will be prime mover of aging. The aging model of one the most popular objects of experimental biology-a fruit fly (Drosophila melanogaster) created by us (http://homebear.ru/en/download.php) , is based on the assumption that the key mechanism of aging is cellularity loss, the speed of which is determined by the parameters of active oxygen forms generation in motoneurons. Aging is an amazing phenomenon and in the course of biology development scientists get more and more interested in studying it. The most intriguing question of this field of knowledge can be formulated as follows: what mechanism provides gradual decrease in viability of a multicellular organism? Development of experimental biology methods aroused a desire to answer it, studying the molecular changes which accompany the aging process. Researchers have revealed many such changes starting from lipofuscin accumulation to telomere shortening [1]. Moreover, the system of mechanisms of the somatic cells programmed death was discovered and its participation in "self-destruction" of the whole organism was proved by the number of observations [5, 14]. The success in the search of processes characteristics of which correlate with age also had a reverse side. A lot of aging theories exaggerating the value of some or another molecular change have sprung up. Redundancy of the existing aging hypotheses pool is evident to the majority of authors trying to analyze the state of things in gerontology [1]. A multicellular organism is a multilevel self-organizing system. Activity of its elements is coordinated by the most complicated network of feedbacks. Any action is accompanied by a loop of gene expression changes, synthesis of hormones, immune and electrophysiological reactions, etc. The majority of them influences fitness. Nevertheless, for understanding of the processes taking place, for example, at digestion of food it is enough to keep in mind not more than ten physiological and biochemical reactions. The dialectics of the cognitive process is such that abstraction from the majority of details allows creating conceptual models which become a basis of the further detailed elaboration, but already without any loss of understanding of the essence of the phenomenon studied. The theorist who is searching for the main laws of biological processes can achieve success only referring the majority of reactions accompanying them to epiphenomena. Distinguishing the group of phenomena essential for aging from epiphenomena accompanying them is one of the main tasks of modern gerontology. We believe that modern methods of mathematical modeling can be the tool for distinguishing them properly. The sense of their application is reproduction of the "external" aging manifestations in silico, first of all of the standard survivor curves , by means of the simplest «internal mechanism». This mechanism will apparently be the most essential aging mover. Naturally "the internal mechanism» modeling should be based on the biological facts without contradicting them. Creating the aging model of one of the most popular experimental biology objects – a fruit fly (Drosophila melanogaster) based on the simplest presuppositions possible was the task of this research. Drosophila melanogaster life expectancy is measured by several weeks. This organism is an insect with complete metamorphosis. All somatic cells of an imago are postmitotic. Nevertheless, drosophila «survivor curves» have the S-shape characteristic for the majority of animals [8, 12]. Aging modeling of the given object is essentially facilitated by the fact that cells responsible for this process are identified reliably enough and that the key role of the free-radical processes in aging [12] is clearly demonstrated. As it is known, the basic source of reactive oxygen species in eukaryotic cells is a respiratory chain of mitochondria. One of the main enzymesantioxidants is superoxide dismutase (SOD), catalyzing superoxide anion transformation into hydro peroxide and oxygen. It is known that the drosophilae, incapable of SOD synthesis are characterized by short life expectancy [16]. In the early nineties of the last century scientists succeeded in breeding drosophila, having appreciable quantities of human SOD, however, their life expectancy practically didn't differ from that of the wild type. Then the technique appeared that allowed to "switch on" SOD expression only in the necessary tissues by means of additional genetic construction. Specific expression of this gene in motoneurons turned out to make life expectancy longer. Moreover, human SOD introduction into motoneurons only returned life expectancy characteristic for the wild type to the flies defective in this enzyme. Motoneurons are convenient for modeling because of the fact that their quantity in one fly is defined precisely enough and is about 80 [11]. It is possible to assume that the natural death of a drosophila occurs due to the motoneurons number decrease to a critical level. The model of cellularity loss of a homogeneous population of postmitotic cells described http://homebear.ru/en/download.php, in our work [7] has served as the basis for creation of the drosophila aging model. Its logical bases are as follows: • Postmitotic cells are capable to generate a number of substances provoking programmed cellular death (PCD)-for example, hydrogen peroxide. Let us call X the total concentration of such apoptosis signals. • At the increase of X quantity up to a certain limit produced during a time interval which can be named a «cycle»(in this particular case the length of one cycle is 24 hours), the mechanism of self-liquidation works • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are weakly interdependent, they will be distributed according to the normal law (Gaussian law). The presence of an asymmetry and an excess at the X distribution does not change the analyzed laws essentially. The main thing is that the function of X

Research paper thumbnail of Age-related cellularity loss in silico

Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be on... more Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of the most reliable mechanisms realizing the program of ageing. A signal starting the program of cellular death (PCD) in a part of cellular population can be an excess of a threshold level of PCD inductor production as a result of stochastic processes. Speed of ageing is regulated by the proportion of average PCD inductor production, variability of this rate and the size of a threshold level of the PCD induction. The developed model allows to study the progress of these processes and their modulation by antioxidants in silico. The simultaneous coexistence a number of contradicting theories of ageing reflects system crisis of modern gerentology. One of the approaches making the construction of the unified theory of ageing easier, can be formation of some basic methodological framework based on obvious premises the majority of biologists accept. Because of the complexity of this problem (that is determined by complexity of the described phenomena) it is possible to suggest to solve partially, considering successively separate sides of the phenomenon of ageing in hope that this activity will facilitate the future synthesis. This work represents the attempt of realization of such approach as applied to to the phenomenon of cellularity loss in postmitotic tissues. Reduction of the number of cells composing tissues and bodies, seems to be one of the simplest and therefore reliable mechanisms of progressing with the years reducing resiliency of a multicellular organism. Importance of this process for ageing mammals is well enough shown [1, 2, 3, 4]. It is also obvious, that ageing of imago of diptera, submitting to the same statistical regularities, as ageing of the majority of other animals, is caused mainly by postmititic tissues ageing [5, 6]. By now enough facts are accumulated for construction of model of age cellularity loss, allowing to take into account delay of this process by geroprotectors. The preconditions of its logic are as follows: • Postmitotic cells are capable to generate the substances provoking programmed cellular death (PCD) [7],-for example, hydrogen peroxide. We shall consider certain substance X (we would not like to concretize its nature up to the description of work of the mechanism of cellularity loss in general). • At the increase of X quantity up to a certain limit produced during a time interval which can be named "cycle", the mechanism of self-liquidation works. • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are mutually weakly dependent, their distribution will submit to the normal law (Gaussian law). As it will be visible from the further statement, presence of asymmetry and excess at distribution of X size does not change analyzed laws essentially. The main thing is that function of distribution X at convergence of argument to infinity asymptotically tends to zero. As such curve does not cross the X-axis, there can be arbitrary large deviationsfrom average X size. • In a cellular population, at an average level of X production that is lower than the threshold, there will be cells producing the amount of X which will exceed «the threshold of self-liquidation». Let's take Uα size (fig. 1.) as the threshold X size at the excess of which the mechanism of self-liquidation is started. Then 1-α (α-the area of light zone) will be equal to the proportion of cells dying during a cycle (as Gaussian curve in figure is normalized, the whole area under it is equal to 1). Shifting size Uα and/or changing σ (the standard deviation from X sizes distribution X size, for the normalized distribution σ = 1), experimenters or evolving alive systems receive an opportunity to adjust speed of cellularity loss, and, hence, the speed of ageing. Even the superficial visual analysis (fig. 1) convinces that insignificant shifts of Uα can cause big changes 1-α or, concretizing the biological sense of considered processes, it is possible to assume that weak repeating influences, constant introduction of small geroprotector dozes for example, are capable to cause significant delay of ageing. Fig. 1. The normalized curve of normal distribution. Methods For quantitative confirmation of the concept stated above the simulated multi-agent model with use of the approaches stated in work [8] was

Research paper thumbnail of CELLULARITY LOSS AND THE DILMAN'S PROBLEM: IN SILICO RESEARCH

We assumed that prolonged trends of hormones concentration increase can be a consequence of funct... more We assumed that prolonged trends of hormones concentration increase can be a consequence of functioning deterioration of glands producing inhibitors of synthesis.
This deterioration results from glands cellularity loss. The experiments in silico carried out with the help of model http://homebear.ru/en/download.php prove that the phenomenon of loss of sensitivity to hormonal signals with the subsequent stop of cycles can be imitated in the elementary modelling system, and in the basis of the given phenomenon, as well as in the basis of the majority of
gerontological phenomena, cellularity loss can lie. The experiments in silico show that, in principle, the diversity of hormonal effects that accompany the realization of the phenoptosis of multicellular organisms can be provided with a simple “software mechanism” This mechanism based on the gradual loss of cellularity as a result of continuous run of apoptosis in some cells of the glands due to natural fluctuations in levels of intracellular inducers of apoptosis. The main practical sense of our work lies in the illustration of the fact that substances inhibiting cellularity loss can theoretically be effective suppressors of hormonal changes characteristic for aging.

Research paper thumbnail of Aging Saves Populations from Extinction under Lack of Resources: in silico

By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question... more By admitting the programmed organism death (phenoptosis) concept, it inevitably raises a question as to what advantages it gives to communities containing elderly and naturally weakened individuals. We believe that the broadest prevalence of the aging phenomenon is accounted for, particularly, by the fact that in certain situations occurrence of elderly individuals may guarantee not only evolution, but also the mere existence of populations. The goal of our study was to create a mathematical model illustrating the occurrence of situations when existence of elderly individuals accounts for population survival, whereas an ageless population would be completely extinguished. A logic basis for such model is as follows: 1) natural populations exist under conditions of uneven renewal of resources; 2) if resources are renewed at a high level and rapidly compensated by their restoration, then a population strives to achieve a maximum size, which is limited not by resource availability, but specific biological mechanisms; 3) rate of resource influx may decline down to zero very rapidly (e.g. during drought); 4) a capacity, at least, for some individuals to survive during resource shortage is crucial for survival of the entire population; 5) rapid extinction of the weaker elderly individuals saves resources for survival of the younger and stronger ones. A multi-agent simulation is used as a mathematical basis for the proposed model (http://www.winmobile.biz). In silico experiments confirmed the lack of fatal contradictions in our logical construction. When the aging program is enabled at age of 25-30 years, it results in increasing population survival by 24-26%. The assumption that in animals aging represented as a slow phenoptosis is a process characterized by decreased viability controlled by a special genetic program turned out to be highly fruitful, primarily, for practical gerontology [1]. A search for the aging program ―switch-off‖ resulted in emerging of a number of promising drugs. Among them, the most effective drug can be used for treatment of a broad range of age-related pathologies,

Research paper thumbnail of Stat1 en

Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be on... more Resume Gradual reduction of the amount of cells constituting postmitotic tissues appears to be one of the most reliable mechanisms realizing the program of ageing. A signal starting the program of cellular death (PCD) in a part of cellular population can be an excess of a threshold level of PCD inductor production as a result of stochastic processes. Speed of ageing is regulated by the proportion of average PCD inductor production, variability of this rate and the size of a threshold level of the PCD induction. The developed model allows to study the progress of these processes and their modulation by antioxidants in silico. The simultaneous coexistence a number of contradicting theories of ageing reflects system crisis of modern gerentology. One of the approaches making the construction of the unified theory of ageing easier, can be formation of some basic methodological framework based on obvious premises the majority of biologists accept. Because of the complexity of this problem (that is determined by complexity of the described phenomena) it is possible to suggest to solve partially, considering successively separate sides of the phenomenon of ageing in hope that this activity will facilitate the future synthesis. This work represents the attempt of realization of such approach as applied to to the phenomenon of cellularity loss in postmitotic tissues. Reduction of the number of cells composing tissues and bodies, seems to be one of the simplest and therefore reliable mechanisms of progressing with the years reducing resiliency of a multicellular organism. Importance of this process for ageing mammals is well enough shown [1, 2, 3, 4]. It is also obvious, that ageing of imago of diptera, submitting to the same statistical regularities, as ageing of the majority of other animals, is caused mainly by postmititic tissues ageing [5, 6]. By now enough facts are accumulated for construction of model of age cellularity loss, allowing to take into account delay of this process by geroprotectors. The preconditions of its logic are as follows: • Postmitotic cells are capable to generate the substances provoking programmed cellular death (PCD) [7],-for example, hydrogen peroxide. We shall consider certain substance X (we would not like to concretize its nature up to the description of work of the mechanism of cellularity loss in general). • At the increase of X quantity up to a certain limit produced during a time interval which can be named "cycle", the mechanism of self-liquidation works. • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are mutually weakly dependent, their distribution will submit to the normal law (Gaussian law). As it will be visible from the further statement, presence of asymmetry and excess at distribution of X size does not change analyzed laws essentially. The main thing is that function of distribution X at convergence of argument to infinity asymptotically tends to zero. As such curve does not cross the X-axis, there can be arbitrary large deviationsfrom average X size. • In a cellular population, at an average level of X production that is lower than the threshold, there will be cells producing the amount of X which will exceed «the threshold of self-liquidation». Let's take Uα size (fig. 1.) as the threshold X size at the excess of which the mechanism of self-liquidation is started. Then 1-α (α-the area of light zone) will be equal to the proportion of cells dying during a cycle (as Gaussian curve in figure is normalized, the whole area under it is equal to 1). Shifting size Uα and/or changing σ (the standard deviation from X sizes distribution X size, for the normalized distribution σ = 1), experimenters or evolving alive systems receive an opportunity to adjust speed of cellularity loss, and, hence, the speed of ageing. Even the superficial visual analysis (fig. 1) convinces that insignificant shifts of Uα can cause big changes 1-α or, concretizing the biological sense of considered processes, it is possible to assume that weak repeating influences, constant introduction of small geroprotector dozes for example, are capable to cause significant delay of ageing. Fig. 1. The normalized curve of normal distribution. Methods For quantitative confirmation of the concept stated above the simulated multi-agent model with use of the approaches stated in work [8] was

Research paper thumbnail of Simulation of Drosophila aging in silico

One of the main tasks of modern gerontology is isolation of a group of phenomena essential for ag... more One of the main tasks of modern gerontology is isolation of a group of phenomena essential for aging from epiphenomenona accompanying them. The modern methods of simulation modeling may be the proper tool for correct isolation. The point of their application is reproduction of external aging manifestations in silico, and, in the first place, of standard survival curves with the help of the simplest internal mechanism. It seems that such a mechanism will be prime mover of aging. The aging model of one the most popular objects of experimental biology-a fruit fly (Drosophila melanogaster) created by us (http://winmobile.biz/moton/en/moto.html) , is based on the assumption that the key mechanism of aging is cellularity loss, the speed of which is determined by the parameters of active oxygen forms generation in motoneurons. Aging is an amazing phenomenon and in the course of biology development scientists get more and more interested in studying it. The most intriguing question of this field of knowledge can be formulated as follows: what mechanism provides gradual decrease in viability of a multicellular organism? Development of experimental biology methods aroused a desire to answer it, studying the molecular changes which accompany the aging process. Researchers have revealed many such changes starting from lipofuscin accumulation to telomere shortening [1]. Moreover, the system of mechanisms of the somatic cells programmed death was discovered and its participation in "self-destruction" of the whole organism was proved by the number of observations [5, 14]. The success in the search of processes characteristics of which correlate with age also had a reverse side. A lot of aging theories exaggerating the value of some or another molecular change have sprung up. Redundancy of the existing aging hypotheses pool is evident to the majority of authors trying to analyze the state of things in gerontology [1]. A multicellular organism is a multilevel self-organizing system. Activity of its elements is coordinated by the most complicated network of feedbacks. Any action is accompanied by a loop of gene expression changes, synthesis of hormones, immune and electrophysiological reactions, etc. The majority of them influences fitness. Nevertheless, for understanding of the processes taking place, for example, at digestion of food it is enough to keep in mind not more than ten physiological and biochemical reactions. The dialectics of the cognitive process is such that abstraction from the majority of details allows creating conceptual models which become a basis of the further detailed elaboration, but already without any loss of understanding of the essence of the phenomenon studied. The theorist who is searching for the main laws of biological processes can achieve success only referring the majority of reactions accompanying them to epiphenomena. Distinguishing the group of phenomena essential for aging from epiphenomena accompanying them is one of the main tasks of modern gerontology. We believe that modern methods of mathematical modeling can be the tool for distinguishing them properly. The sense of their application is reproduction of the "external" aging manifestations in silico, first of all of the standard survivor curves , by means of the simplest «internal mechanism». This mechanism will apparently be the most essential aging mover. Naturally "the internal mechanism» modeling should be based on the biological facts without contradicting them. Creating the aging model of one of the most popular experimental biology objects – a fruit fly (Drosophila melanogaster) based on the simplest presuppositions possible was the task of this research. Drosophila melanogaster life expectancy is measured by several weeks. This organism is an insect with complete metamorphosis. All somatic cells of an imago are postmitotic. Nevertheless, drosophila «survivor curves» have the S-shape characteristic for the majority of animals [8, 12]. Aging modeling of the given object is essentially facilitated by the fact that cells responsible for this process are identified reliably enough and that the key role of the free-radical processes in aging [12] is clearly demonstrated. As it is known, the basic source of reactive oxygen species in eukaryotic cells is a respiratory chain of mitochondria. One of the main enzymes-antioxidants is superoxide dismutase (SOD), catalyzing superoxide anion transformation into hydro peroxide and oxygen. It is known that the drosophilae, incapable of SOD synthesis are characterized by short life expectancy [16]. In the early nineties of the last century scientists succeeded in breeding drosophila, having appreciable quantities of human SOD, however, their life expectancy practically didn't differ from that of the wild type. Then the technique appeared that allowed to "switch on" SOD expression only in the necessary tissues by means of additional genetic construction. Specific expression of this gene in motoneurons turned out to make life expectancy longer. Moreover, human SOD introduction into motoneurons only returned life expectancy characteristic for the wild type to the flies defective in this enzyme. Motoneurons are convenient for modeling because of the fact that their quantity in one fly is defined precisely enough and is about 80 [11]. It is possible to assume that the natural death of a drosophila occurs due to the motoneurons number decrease to a critical level. The model of cellularity loss of a homogeneous population of postmitotic cells describedhttp://www.winmobile.biz/shou/en/demoApp.php, in our work [7] has served as the basis for creation of the drosophila aging model. Its logical bases are as follows: • Postmitotic cells are capable to generate a number of substances provoking programmed cellular death (PCD)-for example, hydrogen peroxide. Let us call X the total concentration of such apoptosis signals. • At the increase of X quantity up to a certain limit produced during a time interval which can be named a «cycle»(in this particular case the length of one cycle is 24 hours), the mechanism of self-liquidation works • The average X quantity, produced in cells during a cycle is lower than «a threshold of self-liquidation». • As X quantities for various cells are weakly interdependent, they will be distributed according to the normal law (Gaussian law). The presence of an asymmetry and an excess at the X distribution does not change the analyzed laws essentially. The main thing is that the function of X distribution at convergence of argument to infinity asymptotically approaches zero. As this curve does not cross the X-axis, there can be arbitrary large deviations from average X size. • In a cellular population, at an average level of X production that is lower than the threshold, there will be cells producing the amount of X which will