How Scientometrics Became the Most Important Science for Researchers of All Specialties.

The point of view of the author of this article, who participates in the work of several scientific journals, on the current situation with publishing articles by scientists of various specialties is presented. Two approaches to this problem are considered: "informal" (focused only on the quality of published manuscripts) and "formal" (taking into account mainly the scientometric indicators of both authors and journals). The continuous commercialization of this process, associated with the emergence of a huge number of publications that require significant article processing charges from scientists to publish the results of their research, is noted. At the same time, the financial interests of publishers promote reducing the requirements for reviewing and editing articles submitted to the editorial board. It is emphasized the need for the appropriate formal scientometric indicators for researchers applying for grants as well as for the corresponding positions and titles, which has arisen at the present stage. According to the author, excessive attention to such formal rankings does not improve the effectiveness of scientific publications, negatively affecting, in particular, the process of blind peer reviewing, grammar and style of manuscripts, statistical processing of data given in articles, design of illustrations, as well as the quality of reference lists.

Protein Poly(ADP-ribosyl)ation System: Changes in Development and Aging as well as due to Restriction of Cell Proliferation.

It is well known that the number of dividing cells in an organism decreases with age. The average rate of cell division in tissues and organs of a mature organism sharply decreases, which is probably a trigger for accumulation of damage leading to disturbance of genome integrity. This can be a cause for the development of many age-related diseases and appearance of phenotypic and physiological signs of aging. In this connection, the protein poly(ADP-ribosyl)ation system, which is activated in response to appearance of various DNA damage, attracts great interest. This review summarizes and analyzes data on changes in the poly(ADP-ribosyl)ation system during development and aging in vivo and in vitro, and due to restriction of cell proliferation. Special attention is given to methodological aspects of determination of activity of poly(ADP-ribose) polymerases (PARPs). Analysis of relevant publications and our own data has led us to the conclusion that PARP activity upon the addition of free DNA ends (in this review referred to as stimulated PARP activity) is steadily decreasing with age. However, the dynamics of PARP activity measured without additional activation of the enzyme (in this review referred to as unstimulated activity) does not have such a clear trend: in many studies, the presented differences are statistically non-significant, although it is well known that the number of unrepaired DNA lesions steadily increases with aging. Apparently, the cell has additional regulatory systems that limit its own capability of reacting to DNA damage. Special attention is given to the influence of the cell proliferative status on PARP activity. We have systematized and analyzed data on changes in PARP activity during development and aging of an organism, as well as data on differences in the dynamics of this activity in the presence/absence of additional stimulation and on cellular processes that are associated with activation of these enzymes. Moreover, data obtained in different models of cellular aging are compared.

Current trends in etiology, prognosis and therapeutic aspects of Parkinson's disease: a review.

Parkinson's disease (PD) is a movement disorder, mainly affecting population consisting of the aged. PD occurs chiefly due to progressive loss of dopaminergic neurons in nigrostriatal pathway. Largely, PD patients suffer from non-motor symptoms, such as depression, anxiety, fatigue, and sleep disorders, that needs further investigation and addressing during PD research. Depression in PD is a predominant and complex symptom, and its pathology exists extrinsic to the nigrostriatal system. This disease can  ultimately be managed by a combination of regular physiotherapy and proper medication. Taking together the present scenario of PD, including the nature of disease, characteristics, treatment, diagnosis of the patients with PD, these outcomes were reviewed to be explored along with many speech-based solutions to PD in this study. This neurodegenerative disorder needs advancement in  research and development which  can help patients with PD to lead a normal life.

Impairment of regeneration in aging: appropriateness or stochastics?

There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. We believe that the restriction of cell proliferation in an aging multicellular organism is not a consequence of implementing a special program of aging. Apparently, such a program does not exist at all and aging is only a "byproduct" of the program of development, implementation of which in higher organisms suggests the need for the emergence of cell populations with very low or even zero proliferative activity, which determines the limited capacity of relevant organs and tissues to regenerate. At the same time, it is the presence of highly differentiated cell populations, barely able or completely unable to reproduce (neurons, cardiomyocytes, hepatocytes), that ensures the normal functioning of the higher animals and humans. Apparently, the impairment of regulatory processes, realized at the neurohumoral level, still plays the main role in the mechanisms of aging of multicellular organisms, not just the accumulation of macromolecular defects in individual cells. It seems that the quality of the cells themselves does not worsen with age as much as reliability of the organism control over cells, organs and tissues, which leads to an increase in the probability of death.

The protein poly(ADP-ribosyl)ation system: its role in genome stability and lifespan determination.

The processes that lead to violation of genome integrity are known to increase with age. This phenomenon is caused both by increased production of reactive oxygen species and a decline in the efficiency of antioxidant defense system as well as systems maintaining genome stability. Accumulation of different unrepairable genome damage with age may be the cause of many age-related diseases and the development of phenotypic and physiological signs of aging. It is also clear that there is a close connection between the mechanisms of the maintenance of genome stability, on one hand, and the processes of spontaneous tumor formation and lifespan, on the other. In this regard, the system of protein poly(ADP-ribosyl)ation activated in response to a variety of DNA damage seems to be of particular interest. Data accumulated to date suggest it to be a kind of focal point of cellular processes, guiding the path of cell survival or death depending on the degree of DNA damage. This review summarizes and analyzes data on the involvement of poly(ADP-ribosyl)ation in various mechanisms of DNA repair, its interaction with progeria proteins, and the possible role in the development of spontaneous tumors and lifespan determination. Special attention is given to the relationship between various polymorphisms of the human poly(ADP-ribose) polymerase-1 gene and longevity.

[Impairment of regeneration in aging: appropriateness or stochastics?].

There is a viewpoint that suppression of the proliferative capacity of cells and impairment of the regeneration of tissues and organs in aging are a consequence of specially arisen during evolution mechanisms that reduce the risk of malignant transformation and, thus, protect against cancer. At the same time, senescent cells of the body begin to accumulate a variety of macromolecular defects, which, conversely, increase the likelihood of their transformation into cancer cells. Thus, according to the point, the restriction of cell proliferation is a double-edged sword, which, on the one hand, reduces the likelihood of developing cancer at an early age, but on the other hand--limits life span due to the accumulation of "damaged" cells in old age. However, it remains unclear why normal human cells in vitro, with none of the mentioned "anticancer" barriers functioning at the organismal level only, NEVER undergo spontaneous malignant transformation. In addition, it is also unclear how the freshwater hydra which, under certain conditions, has really no postmitotic and senescent cells, escapes both aging and cancer and, at such conditions (excluding the need for sexual reproduction), can live almost indefinitely, having a great regenerative potential (new organism can arise even from a 1/100 of the old one). I believe that the restriction of cell proliferation in an aging multicellular organism is not a consequence of implementing a special program. Apparently, there is no special program of aging. It is only a "byproduct" of the program of development, implementation of which in higher organisms suggests the need for the emergence of cell populations with very low or even zero proliferative activity, which determines the limited capacity of relevant organs and tissues to regenerate. At the same time, it is the presence of highly differentiated cell populations, barely able or completely unable to reproduce (neurons, cardiomyocytes, hepatocytes), that ensures the normal functioning of the higher animals and humans. Even the regeneration of these organs with the help of stem cells could lead to a breach of the necessary interactions in complex systems. Reductionism in experimental-gerontological research ("everything is determined by deleterious changes in single cells") that has become widespread in recent decades, stimulated the emergence of a number of model systems for studying mechanisms of aging in isolated cells (Hayflick phenomenon, the model of "stationary phase aging", the cell-kinetic model for testing geroprotectors and geropromoters, etc.). However, at present it seems that the data obtained in such models cannot be automatically applied to the situation in the whole organism. Apparently, the impairment of regulatory processes, realized at the neurohumoral level, still plays the main role in the mechanisms of aging of multicellular organisms, not just the accumulation of macromolecular defects in individual cells. It is possible that it is the deterioration of such regulation that may be the cause of the observed abnormal INCREASE of the intensity of proliferation of some cell populations in old age, resulting in senile acromegaly and age-related rise of numerous benign tumors. It seems that the quality of the cells themselves does not worsen with age as much as reliability of the organism CONTROL over cells, organs and tissues, which leads to an increase in the probability of death.

[What will happen to molecular cell biomarkers of aging in case we cancel its program (of course, if it does exist)?].

Currently, gerontologists, evaluating the effectiveness of various impacts on the aging process, as a rule, use a variety of molecular cell biomarkers of aging. This provides much more rapid results than in the case of the survival curve obtaining. However, in many cases the usefulness of these biomarkers of aging is grounded in works devoted to what is called cellular/cell senescence. Unfortunately, the evolution of the term in recent years has led to the loss, to a large extent, of its original meaning, that is the changes of the cells during their replicative senescence ("on Hayflick's grounds"), similar to the changes of cells in the aging organism. At present, most of the work in this area is related to the induction of the relevant changes in the cells (usually transformed) by various DNA damaging factors. Such an approach, although is very important to define a strategy to fight cancer, but, yet again, takes us away from the study of the real mechanisms of organismal aging. In addition, there are reasons to believe that the biomarkers of aging, proposed by these studies (and in particular, the most popular of them--the activity of senescence-associated beta-galactosidase), are related, as a rule, to the proliferative status of the cells, which in the whole body is generally determined by proper implementing the program of development and differentiation, leading to the emergence of tissues and organs composed of postmitotic or very slowly proliferating cells. Therefore, the possible disabling the aging program, apparently, will not lead to any changes in the age dynamics of those biomarkers of aging. This conclusion brings us back to the need for obtaining the survival curves of experimental animals or humans as the only true (although the most time- and money-consuming) approach to evaluating the effectiveness of the modification of the aging process.

[Effect of gold nanoparticles on mouse spermatogenesis].

The response of the mouse male germ cells exposed to gold nanoparticles (approximately 2.5 nm) was studied. Our investigation demonstrates that treatment with Au nanoparticles for four days does not impair the architecture of the spermatogenic epithelium. Cytogenetic evaluation using micronucleus assay showed that gold nanoparticles can affect the chromosomes of early primary spermatocytes. However, gold nanoparticles did not induce chromosome abnormalities in spermatogonial stem cells. Further, the cauda epididymal sperm was isolated on the 14th day after treatment and was incubated in SDS solution (Na sodium dodecyl) and then in a solution containing DTT (dithiothreitol) to induce nuclear chromatin decondensation. Observations showed that after four days of treatment of spermiogenic (postmeiotic) cells with gold nanoparticles the decondensation process had no differences from the control. On the contrary, in the experiment with the same cells and period of fixation but with a single exposure to gold nanoparticles, the number of mature gametes with totally decondensed nuclei reached 100% as opposed to 44% in the controls.

Teaching cytogerontology in Russia and China.

Approaches to teaching the cell biology of aging (cytogerontology), within the appropriate agreements by scientists of the School of Biology of Moscow State University and at the Department of Life Science and Engineering of Harbin Institute of Technology (China), are described. The authors draw attention to certain differences in teaching biology between the two institutions and emphasize the significance of a system approach to teaching cytogerontology. This approach makes it absolutely necessary to introduce the course on the basics of biology of aging. It is concluded that full perception of the data from modern molecular cell cytogerontological research, by the students from both institutions, is impossible without understanding the fundamental notions and definitions used in both theoretical and experimental gerontology.

[From Carrel to Hayflick and back or what we got from the 100 years of cytogerontological studies].

The history of experimental-gerontological studies on cultured cells is reviewed. Comparative analysis of cytogerontological investigations and/or gerontological theories of Weismann, Carrel, Hayflick, and the paper author is carried out. It is emphasized that in XX century the theories' nature has changed abruptly many times. It is concluded that at the moment it is almost impossible to explain with the help of the cytogerontological studies' results how multicellular organisms age. The necessity of obligatory combination of experiments on cultured cells with fundamental gerontological investigations, including survival curve analysis for humans or experimental animals is supposed.

[Ageing of the spermatogenesis system].

This review summarizes the data characterizing the effect of ageing on the development of male germ cells and their hereditary structures. We have studied causes of spermatogenesis reduction at late stages of ontogenesis. We have focused on age-specific changes of the structural-functional integrity of stem spermatogonial cells and their microenvironment (niche). We also examined several unique and specific features of the spermatogenic system in senescence-accelerated mutant mice (SAM), with accelerated ageing.

[8-oxo-2'-deoxyguanosine accumulation in DNA from "stationary phase aging" cultured cells].

The 8-oxo-dG/dG ratio in DNA of cultured transformed Chinese hamster cells was analyzed during their "stationary phase aging". Amount of 8-oxo-dG and dG in DNA hydrolyzate was evaluated by HPLC-EC. The cells grew and "aged" for 15 days. As expected, the 8-oxo-dG/dG ratio increased with cell "age". It did not change significantly from 4th to 8th day (6.26 x 10(-5) and 4.42 x 10(-5), correspondingly) and then abruptly increased to 15th day of "age" (22.40 x 10(-5)). The results are in accordance with the conception of cell proliferation restriction as the starting mechanism of ageing and the method can be used for evaluation of cell culture biological age when testing new compounds for their geroprotector or geropromoter activity.

[Potential geroprotector properties of the extract of reindeer antler powder in experiments on cultured cells].

Preparations from deer antlers are well known by their multiple medicinal properties. In particular, their health-giving effect on senescing organism has been repeatedly shown. In the study we investigated effect of water extract of reindeer mature antler powder (ERAP) on the kinetics of growth and "stationary phase aging" of HeLa (clone 11) cell line. Cell suspension was placed in the wells of 24-well plastic tissue culture plates with seeding density of 15 10(3)/cm2. The growth medium contained ERAP at 0, 10 or 100 microl/ml. In every 1-3 days microscopic evaluation of live cell number in the wells has been made. It turned out, that ERAP at 10 microl/ml increased proliferation rate of HeLa cells as well as their saturation density, i.e. acted as a geroprotector. The result was also confirmed by the observed "stationary phase aging" slowing down leading to increase of the "average life span" of cell culture. However, effect of ERAP at 100 microl/ml was different. In that case the evident decrease of cell culture saturation density was observed indicating increase of the culture "biological age". Besides, the cell death began earlier leading to decrease of the "average life span" of the cell culture. We think that ERAP contains some compounds with geroprotector activity as well as some geropromoters, or cell proliferation inhibitors. At the lower ERAP concentration in growth medium content of geropromoter(s) is too low for its effect manifestation and the evident "rejuvenation" of the cell culture is observed. At the higher concentration of ERAP (100 microl/ml) the content of geropromoter(s) reaches the "working" value and this not only masks the effect of geroprotector(s) but also leads to the cell culture "senescence".

Poly(ADP-ribose)-polymerase-1 and aging: experimental study of possible relationship on stationary cell cultures.

Experiments on "stationary aging" cultures of B11dii-FAF28 Chinese hamster cells showed that contact inhibition of cell growth and further culturing of cells in the stationary phase led to continuous inhibition of enzymes realizing poly-ADP-ribosylation of chromatin proteins. Cell density in the monolayer and percentage of damaged cells detected by trypan blue staining decreases during this process.

["Stationary phase aging" of cell culture: an attempt of evaluation of growth medium "age" effect].

Cell proliferation rate and 3H-thymidine labeling index of "young" (i. e. harvested in 3 days after subcultivation) cultured Chinese hamster cells (B11 dii-FAF28 line) have been determined in growth medium conditioned by the same cells for various periods of time during their growth and subsequent "stationary phase aging" (medium of different "age"). Cells were serially cultured in Eagle's medium with 10 % bovine serum. The experiment was conducted as follows. The "young" cells were seeded in Carrel's flasks (4500 cells/cm2) with fresh growth medium and placed at 37 degreesC. At definite time intervals, media from 3 randomly selected flasks were filtrated and stored in small glass flasks at 4 degreesC. The cells from all 3 flasks were collected by trypsin treatment and counted with hemocytometer. During the period of 26 day cultivation we collected a set of media of different "age" corresponding to certain points of the growth and "stationary phase aging" curve of the culture. Then, the "young" cells in fresh medium were seeded into tissue culture plates with cover slips placed into wells of the plates (26,600 cells/cm2) and grown at 37degreesC, 5 % CO2 for 2 h. At this point, the medium was replaced with media of different "age". 22 h later (i. e. on the first day after seeding) cell density was evaluated microscopically in all the wells. On the next day (i. e. in 2 days after seeding) 3H-thymidine was added to every well to final concentration 1.85 x 10(4) Bq/ml. After next 24 h (i. e. in 3 days after seeding) cell density was counted again, and the medium was removed. The cover slips were rinsed with Hank's solution and air-dried. Autoradiography was performed in standard manner by photoemulsion exposing for 5 days and subsequent developing in amidol developer. The relative number of nuclei with 10 and more "grains" was revealed microscopically. Based on the obtained results, two basic parameters were evaluated for every "age" medium: 1) cell proliferation activity index calculated as log2 (N3/N1), where N1 - cell density on the first day after seeding, and N3 - the same parameter on the third day after seeding; 2) cell labeling index calculated as percentage of cells with nuclei labeled by 3H-thymidine during incubation from 2nd to 3rd day of cultivation. These two indexes for cell growth in different "age" media appeared to be highly correlating (R = 0.85). Besides, it was found that the observed "age-related" diminishing of ability of the growth media of different "age" to stimulate proliferation of "young" cells cannot completely explain the "stationary phase aging" phenomenon (in particular, even for the "oldest" medium cell labeling index was 65 %). We conclude that the phenomenon is based on exactly intrinsic changes of cells, most likely on molecular level, though environmental effects cannot be entirely excluded. The authors are grateful to the Russian Basic Research Foundation for support (grants 03-04-49030 and 00-04-48049).

[Cytogerontology at the beginning of the third millenium: from "correlative" to "gist" models]. / Tsitogerontologgie v nachae tret'ego tysiacheletiia: ot "korreliativnykh" i "sushchnostym" modeliam.

For the most part, research in the area of cytogerontology, i.e., investigation of the mechanisms of aging in the experiments on cultured cells, is carried out using the "Hayflick's model". More than forty years have passed since the appearance of that model, and during this period of time, very much data were obtained on its basis. These data contributed significantly to our knowledge of the behavior of both animal and human cultured cells. Specifically, we already know of the mechanisms underlying the aging in vitro. On the other hand, in my opinion, little has changed in our knowledge of the aging of the whole organism. In all likelihood, this can be explained by that the Hayflick's model is, like many others used in the experimental gerontology, correlative, i.e. based on a number of detected correlations. In the case of Hayflick's model, these are correlations between the mitotic potential of cells (cell population doubling potential) and some "gerontological" parameters and indices: species life-span, donor age, evidence of progeroid syndromes, etc., as well as various changes of normal (diploid) cells during long-term cultivation and during aging of the organism. It is, however, well known that very frequently a good correlation has nothing to do with the essence (gist) of the phenomenon. For example, we do know that the amount of gray hair correlates quite well with the age of an individual but is in no way related to the mechanisms of his/her aging and probability of death. In this case, the absence of cause-effect relationships is evident, which are, at the same time, indispensable for the development of gist models. These models, as distinct from the correlative ones, are based on a certain concept of aging. In the case of Hayflick's model, such a concept is absent: we cannot explain, using the "Hayflick's limit", why our organism ages. This conclusion was convincingly confirmed by the discovery of telomere mechanism which determines the aging of cells in vitro. That discovery initiated the appearance of theories attempting to explain the process of aging in vivo also on its basis. However, it has become clear that the mechanisms of aging of the entire organism, located, apparently, in its postmitotic cells, such as neurons or cardiomyocytes, cannot be explained in the framework of this approach. Hence, we believe that it is essential to develop "gist" models of aging using cultured cells. The mechanisms of cell aging in such models should be similar to the mechanisms of cell aging in the entire organism. Our "stationary phase aging" model could be one of such models, which is based on the assumption of the leading role of cell proliferation restriction in the processes of aging. We assume that the accumulation of "senile" damage is caused by the restriction of cell proliferation either due to the formation of differentiated cell populations during development (in vivo) or to the existence of saturation density phenomenon (in vitro). Cell proliferation changes themselves do not induce aging, they only lead to the accumulation of macromolecular defects, which, in turn, lead to the deterioration of tissues, organs, and, eventually, of the entire organism, increasing the probability of its death. Within the framework of our model, we define cell aging as the accumulation in a cell population of various types of damage identical to the damage arising in senescing multicellular organism. And, finally, it is essential to determine how the cell is dying and what the death of the cell is. These definitions will help to draw real parallels between the "genuine" aging of cells (i.e., increasing probability of their death with "age") and the aging of multicellular organisms.

[Results and perspectives of cytogerontologic studies in modern time]. / Itogi i perspektivy tsitogerontologicheskikh issledovanii na sovremennom étape.

The overwhelming majority of research in the field of cytogerontology (i.e. investigating mechanisms of aging in experiments with cultured cells) has been done using the widely applied Hayflick's model. More than 40 years have passed since the appearance of the model, and during this time numerous data were obtained on its basis. The data significantly contributed to our knowledge of the behavior of cultured animal and human cells. In particular, we know enough about the in vitro aging phenomenon. But in my opinion, little has changed in our knowledge of aging in the whole organism. This may be, presumably, because Hayflich's model, like many other models used in experimental gerontology, is correlative, i.e. based on a great variety of detected correlations. In Hayflick's model these are correlations between the cell mitotic potential (cell population doubling potential) and the number of "gerontological" parameters and indices, such as the species life span, donor's age, evidence of progeroid syndromes, etc, and also correlations between various changes of normal (diploid) cells during a long-term cultivation and in the course of organismal aging. However, it is well known that a good correlation does not frequently have anything in common with the essence (gist) of the phenomenon under investigation. For example, the amount of grey hair in the individual is known to excellently correlate with his or her age, being, however, in no way associated with mechanisms of aging or probability of death. In this case, the absence of cause-effect relationships is evident. But it is these particular relationships that are totally indispensable for gist models developing. Such models, different from the correlative ones, are based on a definite concept of aging phenomenon. With the Hayflick's model, such a concept is absent, since using "Hayflick's limit" one cannot explain why the human organism is aging eventually. This can be exemplified by a discovery of a telomere mechanism, which is claimed to determine cell aging in vitro. This discovery triggered an outburst of theories aimed to explain on its basis as well the process of aging in vivo. However, now it is clear that mechanisms of the whole organism aging, hidden, presumably, in its postmitotic cells (neurons or cardiomyocytes) cannot be accounted for by this approach. In view of all stated above, we consider as indispensable the elaboration of "gist" models of aging using cultured cells. Mechanism of cell aging in these models must be similar to those in the whole organism. We believe that one of such models may be our "stationary phase aging" model, based on an assumption of the leading role of cell proliferation restriction in aging. We assume that accumulation of "senile" damage may by caused by the restriction of cell proliferation due to both the formation of differentiated cell populations in the course of development, and the existence of saturation density phenomenon (in vitro). Cell proliferation changes by themselves do not induce any aging processes, but lead only to accumulating macromolecular defects, which in their turn generate deterioration of tissues, organs, and eventually of the whole organism, thus increasing the probability of its death. Within the framework of our model, we define cell aging as the accumulation in a cell population of different types of damage identical to the damage arising in senscencing multicellular organism. And finally, we consider as very important the future studies aimed to determine the process of cell dying and cell death in general. Availability of such definitions would help to draw real parallels between the "genuine" cell aging (i.e. the increased probability of cell destruction with "age") and aging of the multicellular organism.

[Enzymatic synthesis of beta-NAD+ selectively marked with tritium at adenine and its use for determining the activity of poly(ADP-ribose) polymerase]. / Fermentativnyi sintez selektivnomechennogo tritiem po adeninu beta-NAD+ i ego ispol'zovanie dlia opredeleniia akativnosti poli(ADF-riboza)-polimerazy.

A method of preparation of tritiated beta-HA [symbol: see text]+ from (adenine-2,8-(3)H)ATP and nicotinamide mononucleotide is suggested. This method is based on the baker's yeast (Saccharomyces cerevisiae) enzyme nicotinamide nucleotide adenylyltransferase. Experimental conditions for a nearly complete conversion of labeled ATP to NAD were determined. The tritiated NAD prepared by this method can be used in the quantitative assay of the chromatin enzyme poly(ADP-ribose) polymerase.

[Algorithmic support of a laboratory bed for testing geroprotectors and geropromoters]. / Algoritmicheskoe obespechenie ispytal'nogo stenda dlia testirovaniia geroprotektorov i geropromotorov.

The paper proposes a mathematical model of development of a cell population with a changing proliferative activity. The model is based on the Markov branching process with cells of several types. A procedure for identifying the constructed model by experimental evidence is being developed. An example of model construction and assessment for cultured diploid fibroblasts is given.