Genotoxic and cytotoxic drugs, widely used in anticancer therapy, target proliferating cells and induce cell death through a variety of cell cycle-dependent mechanisms. The mechanisms of the delayed toxicity induced by chemotherapy are not fully understood. The accumulation of senescent cells may underlie some of the mechanisms for the development of late adverse effects of chemotherapy on muscle tissue. Cellular models are necessary for the development of therapeutic approaches to these side effects. In our study we used human immortalized myoblast MB135 to optimize the protocol for obtaining the senescent phenotype of muscle cells under the influence of chemotherapeutic drugs such as doxorubicin, cisplatin and arsenic trioxide (As 2 O 3 ). We evaluated the dynamics of changes in senescence proteins pRb, p21 and p53 and SASP-associated proteins such as TNF, IL-1b, IL-6, IL-8, CXCL2, GDF15 using Western blot, RT-PCR and ELISA. Cell senescence was confirmed by the measurement of cell senescence index by flow cytometry after 7 days of exposure to chemotherapeutic agents. The obtained results indicate that all three investigated chemotherapeutic compounds induce the appearance of senescence markers, but the dynamics of these changes are somewhat different for them, which may reflect differences in the mechanisms of senescence phenotype induction.
The search for and testing of drugs with senolytic activity is a new direction in gerontology. The increasing number of “senescent” cells with age contributes to the development of age-related diseases and chronic non-infectious inflammation. Removing “senescent” cells or suppressing their influence on surrounding tissues seems like a logical step to improve quality of life and possibly prolong it. However, drugs with senolytic and senomorphic activity in model systems induce the development of a number of side effects in clinical trials. In this review, we discuss the main advances in senotherapy, the prospects for the use of senotherapeutics, and the limitations that researchers and clinicians may encounter.
Background. The field of gerontology is actively seeking senolytics and senomorphs that can influence the quantity and activity of senescent cells in the body. Previous studies have demonstrated the geroprotective properties of mitochondrial- directed compounds based on plastoquinone and berberine in various in vitro and in vivo models. Thus, it is plausible that SkQBerb, a mitochondrialtargeted compound combining berberine and plastoquinone, may exhibit higher geroprotective potential compared to previously studied compounds.Objective. The aim of this study is to investigate the geroprotective activity of SkQBerb in a chronological aging model using MB135 myoblasts.Materials and Methods. The effect of SkQBerb on various aging characteristics of human MB135 myoblasts was assessed. Histochemical staining for β-galactosidase was performed using a commercially available kit. The levels of proinflammatory cytokines IL-6 and IL-8 were determined using pre-made immunoassay kits. Additionally, Western blotting was employed to evaluate the levels of p21, pRb (Ser807/811), and LC3B proteins.Results. Analysis of the results revealed that SkQBerb, at concentrations ranging from 20–100 nM, effectively suppressed the accumulation of senescent cells in MB135 cells subjected to chronological aging. Furthermore, it significantly reduced the levels of IL-6 and IL-8, key factors associated with the secretory phenotype.Conclusion. The findings of this study suggest a potential geroprotective and senomorphic effect of SkQBerb. These results open up possibilities for utilizing this mitochondrial-targeted compound as a geroprotector in future applications.
Studying the functioning of various body systems in different vertebrates is one of the key tasks of comparative physiology. Teleost fishes are a large group of vertebrates; however, the mechanisms of their digestive tract functioning are poorly understood and are known mainly for such a model object as Danio rerio. The aim of this work was to characterize the participation of various subtypes of M-cholinergic receptors and the Rho-kinase enzyme in the cholinergic contraction of the smooth muscle of the intestine of the White Sea cod Gadus morhua marisalbi (Gadidae). A longitudinal strip was cut out from the proximal intestine and placed in the device for recording contractile responses in the isometric mode. Contractile reactions in response to acetylcholine were completely blocked by atropine. The blockade of M3-cholinergic receptors with 4-DAMP resulted in a decrease in acetylcholine-induced contraction compared to the control response. The blockade of M1-receptors with pirenzepine also decreased contractile responses, but the effect was less pronounced compared to the effect of M3-cholinergic receptor blockade. The blockade of M2-cholinergic receptors with methoctramine did not affect the magnitude of the contractile response. The incubation of preparations with the Rho-kinase inhibitor was accompanied by a significant decrease in contractile responses compared to the control as well as a more rapid decrease in the contraction force after reaching the “peak” response. Thus, acetylcholine causes contraction of cod intestinal smooth muscle by activating M3- and M1-but not M2-cholinergic receptors. The activity of the Rho-kinase enzyme contributes to the development and maintenance of cod intestinal smooth muscle contraction under the action of acetylcholine. The obtained results are of interest for comparative physiology; they may be important for understanding the mechanisms of the damaging effect of environmental factors on the organism of teleost fish as well as for the use of fish in preclinical studies of drugs.
Circadian rhythms ensure the synchronization of the physiology of cells and tissues in accordance with daily changes in the environment. These rhythms are maintained by transcriptional oscillators located in various organism cells. One of the rhythm sensors for the circadian clock is the intake of nutrients, this synchronizer is especially important in peripheral tissues. With age, the work of both the central and peripheral clock is disturbed. In old age, the amplitude of rhythms decreases and the peaks of expression of clock genes shift. Such changes affect not only the circadian, but also other rhythms. Promising ways to maintain circadian rhythms are a variety of dietary patterns, including both calorie restriction, well known for its ability to prolong the lifespan of laboratory animals, and time-restricted feeding. It is now known that intracellular metabolic sensors are also involved in regulation of the circadian clock. Among these sensors, it should be especially noted AMPK, which coordinates many catabolic and anabolic processes and participates in the implementation of the effect of calorie restriction. It is assumed that non-drug modulation of AMPK activity will not only help fight metabolic disorders, but also maintain circadian rhythms. The review considers the role of AMPK and some other metabolic sensors in the regulation of the circadian clock.
The loss of access to the two main international scientometric databases, Web of Science and Scopus, has set the task for scientific organizations and foundations to find alternative ways to assess the scientific productivity of scientists. Currently, a White List has been created as such an alternative, but further development of our own systems for evaluating journals and our own scientometric indicators is required. So far, we can still see the position of our journals and the level of publication activity according to Scopus, but in the future it will be necessary to find sources of information independent of closed commercial resources to create our own system.
The authors try to consider the current situation with experimental gerontological research aimed at finding means to slow down aging and prolong life (geroprotectors/anti-aging drugs). The importance of correct defining aging as a set of age-related changes in the body, leading to an increase in the probability of its death, is emphasized, as well as the importance of attention to which lifespan (average, maximum, median, species-specific) changes under the influence of geroprotectors. It is noted that prolonging the life of non-aging animals with an exponential survival curve can hardly be considered a geroprotective effect. It is emphasized that the rate of aging and lifespan are not always strictly related, so the impact on one of these two indicators does not necessarily affect the second. The methodological aspects of works devoted to the study of the influence of diet restriction/modification on aging and lifespan are analyzed. The need for correct selection of a control group of animals in experimental gerontological studies is noted. According to the authors, such animals should not have any pathologies or genetic defects in order to exclude the possible influence of the studied factors on such abnormalities, and not on the aging process per se. In this regard, the authors do not consider antibiotics or drugs/vaccines against COVID-19 to be geroprotective, although the former led to the most significant increase of average lifespan in the 20th century, and the latter offset its decline in recent years caused by this infection. It is noted that the current situation in experimental gerontology makes it very desirable to have a thorough discussion on the question of what can still be considered geroprotectors/anti-aging drugs. It is proposed to organize such a discussion in the journal Advances in Gerontology.
The question of the possible influence of the number of views / downloads of scientific articles from journal websites, as well as the number of their mentions in social networks on the number of subsequent citations of these publications is considered. In particular, an analysis of some of such correlations is carried out on the example of 39 Russian translated journals of biological orientation distributed by the Springer Nature publishing house. Data from 2019–2021 was used regarding the number of article downloads, impact factors of editions, their SJR, CiteScore, SNIP, and usage factors. An analysis of the results obtained, as well as data available on the Internet, allowed the authors to conclude that the relationship between the number of downloads or altmetrics and the number of citations is not very strong, although it is quite reliable. It is emphasized that at present a large number of downloads / views of articles are carried out by users who are not engaged in science and, accordingly, do not write articles for academic journals. They are simply interested in scientific research results, and the Internet is now available to almost anyone. This also applies to the discussion of scientific publications in social networks. Apparently, the frequent mention of work in such networks really stimulates its downloads – however, this becomes obvious only if the article is an open access one, because the majority of “law-abiding” users of social networks do not have legal access to publications in subscription editions. The mentioned circumstances, according to the authors, will lead to a gradual weakening of the correlations considered in the article.
The article processing time is currently one of the main characteristics that authors take into account when choosing a journal. In a competitive environment, journals, especially those with low rankings, need to process articles quickly to be attractive to authors. Most charge-free journals are significantly slower in terms of speed than journals with article processing charges (APC), and this is not only due to the fact that some journals with APC publish articles without peer reviewing and editing, but also because paid journals with peer reviewing and editing employ specialists who deal exclusively with the journal. Many domestic journals cannot afford to hire such free-from-other duties specialists, so the articles are processed by employees of the founding organization, who are also involved in scientific and educational work, which is why editorial processes are uneven. Also, article publication time is increased by volume restrictions related to the obligations of subscription publications and publication of the journal strictly by issues (especially if journal publishes issues every two months, quarterly, or less often). This paper compares the article processing time in four biology journals with different financial models from four countries. As expected, the article processing time in journals with APC was expectedly shorter than in charge-free ones. There is a noticeably long wait for paper publication after its acceptance in the journal, which publishes a printed version and releases articles not as they are ready but only as part of the finished issue. The article discusses possible ways to reduce processing time in charge-free journals. However, such a reduction should be adequate; editorial processes should not be expedited at the expense of the quality of editing and peer review.
The authors divided scientific journals into two main categories – “herbivore journals” (subscription journals that do not charge authors for the publication of their articles) and “predatory journals” – paid journals that adhere to unscrupulous editorial and ethical policies. Accordingly, “predatory publishers” are those companies that publish “predatory journals”. As a rule, articles by these publishers are published in the open access mode. The criteria by which scientific publications are classified as “predatory” are considered. It is emphasized that the “charging” nature of the publication does not necessarily make it “predatory”, but creates a situation in which the publisher using the “gold” open access is almost always interested in the maximum number of published works with a significant reduction in the quality requirements for manuscripts sent to the editorial office. The situation with the Jeffrey Beall’s list is briefly considered – the history of its appearance, the criteria for including publishers and some individual journals in it, possible reasons for the abolition, access to the list today. The possible reasons are analyzed why scientists publish in paid journals instead of submitting their articles to free subscription editions, the rating of which, as a rule, is even higher. Considerations of the authors of this article regarding the clear non-obviousness of the advantages of publications in the open access mode for a lot of money are outlined. The current situation with the MDPI publisher, which is very popular among modern scientists and which Jeffrey Bill (and not only him) nevertheless refers to as “predatory” is considered in detail. It is emphasized that the established principles of the existence of “predatory journals” primarily satisfy the authors of the articles themselves, who are attracted by both the speed and the “high guarantee” of the publication process.
At the end of last year and the beginning of this year, our journal Vestnik Moskovskogo Universiteta. Seriya 16. Biologiya celebrated two memorable dates—the anniversary of the entire edition and the anniversary of our series. During its long history, the Vestnik of the School of Biology of Moscow State University has undergone many changes. The goals for which it was created have been modified in the last 15 years, and now the journal is no longer an edition to cover the activities of just scientists working at Moscow State University but is an international edition (the English version is distributed by the Springer Nature publishing house) and is open to publications by authors from any scientific institution either in Russia or other countries. Despite the difficulties that any university editions face, such journals can still develop and occupy their niches among scientific periodicals. Like Chinese scientific editions of the kind, our domestic journals are now continuously working to gain worldwide recognition. In the future, all scientific periodicals are likely to continue to change and transform, the task of university journals is to be in time to develop along with new technologies, taking into account the experience of foreign editions and not forgetting their own rich history.
Despite the great interest of scientists in the question of what cell aging is and the long history of its study, there are still many contradictions in this area. They arise because several different approaches to modeling aging in vitro have been developed. As a result, even different terms arose: cell senescence and cell aging . There are not only differences between models for studying aging at the cellular level; they also have common features. Moreover, it is now becoming apparent that some models complement others. This is evidenced, in particular, by the fact that biomarkers used in one model are suitable for use in another model (aging-associated β-galactosidase, lipofuscin, etc.). The approaches to studying cellular aging developed unevenly, and currently studies on this topic are experiencing another rise due to the prospects for the use of senolytics (drugs that selectively eliminate “senescent” cells) to increase the lifespan of multicellular organisms. This review considers the pros and cons of various models for studying aging on cultured cells of various nature.
The peer review process is an extremely important and time-consuming step in preparing a manuscript for publication. It often takes longer than all other stages of article processing. Due to the complexity of peer reviewing, it becomes necessary to analyze it and determine the key points that you should pay attention to when planning the work of the editorial office. In this study, the authors used data obtained in the process of work with reviewers of the journals “Vestnik Moskovskogo Universiteta. Seriya 16. Biologiya” and “Moscow University Biological Sciences Bulletin” in 2017–2021, as well as information on articles received by the editorial office in the same period time. The sample of peer reviewers consisted of 319 specialists from various fields of biology and related disciplines. The results of the analysis showed that the average time spent on the primary review was about 11 days, and the average time during which experts respond to the invitation was about 2 days. Reviews received by the editors over five years, on average, contain a little less than 3 000 characters, the volume of reviews does not correlate with the timing of the reviews and their quality. In recent years, the editorial office has managed to reduce the proportion of formal uninformative reviews to 6 %. Both women and men, employees of both universities and research institutes, scientists with candidate and doctoral degrees are equally involved in the work on articles. The important role of reviewers in improving the article and at the same time insufficient encouragement of this important work are emphasized. The results obtained can be useful to the editors of scientific journals when they plan the stages of reviewing articles.
Aging is an urgent healthcare issue in view of the rapid growth of the proportion of older persons. Searching for reliable aging biomarkers and prolonging lifespan are increasingly important scientific directions. Experimental gerontology helps to explore fundamental facts which are not always applicable in clinical scenarios. As an example, caloric restriction is one of the key interventions that prolongs laboratory animals’ lifespan and ameliorates some, but not all, aging biomarkers in humans. Consequences of overeating such as obesity, insulin resistance, type 2 diabetes, and metabolic syndrome are taking their toll with aging, making caloric restriction a hot topic in gerontology and geriatrics. Nevertheless, caloric restriction is not widely applicable in view of poor adherence to and limitations of strict diets. Drugs mimicking caloric restrictions, the so-called caloric restriction mimetics, are developed to overcome these limitations. Caloric restriction alone is not a panacea since metabolic pathways are complex and not responsive to a single intervention. Fasting and exercising are additional options for reducing effects of excessive intake of calories. Arguably, physical activity significantly improves the quality of life at old age and delays the onset of overt insulin resistance and associated diseases. Thus, developing optimal fasting and exercising schemes is becoming increasingly important. Such interventions are confounded by a number of factors, including circadian and other biorhythms and baseline metabolic activity. It is justifiable to test fasting and exercising in experimental animals to reveal numerous confounding factors. A hypothesis in this article points to the role of complex interventions such as moderate and balanced diet, intermittent fasting, and physical exercise adjusted to circadian rhythms for prolonging life and improving quality of life. The hypothesis may shed light on fundamental mechanisms of aging and perspectives of anti-aging drug therapies.
The article is devoted to the problem of assessing the quality of scientific publications. It is emphasized that the formal ranking of an article is currently determined, as a rule, not so much by the data obtained or formulated concepts, as by the scientometric indicators of the corresponding journals. Approaches to determining the ranking of an article based on the analysis of its citation (impact factor and its analogues) and the number of mentions in social networks (so called altmetrics), as well as the number of downloads of the paper from the publisher’s website are considered. The authors emphasize the significant role of the appearance of author-paid articles in the current change in the situation with scientific publications. It is assumed that the thorough commercialization of the process of publishing their works by scientists has led to a serious deterioration in their scientific component due to the reducing requirements for the format and content of manuscripts sent to the editors of paid journals. The authors express the hope that the “informal” approach to the evaluation of scientific articles, which is based on their content, but not the ratings of the editions that published these works, has not lost its relevance even at the present stage.
Correction to: “Chinese hamster cells in biotechnological and gerontological research” https://vestnik-bio-msu.elpub.ru/jour/article/ view/933
This review discusses genetic and molecular pathways that link circadian timing with metabolism, resulting in the emergence of positive and negative regulatory feedback loops. The Nrf2 pathway is believed to be a component of the anti-aging program responsible for the healthspan and longevity. Nrf2 enables stress adaptation by activating cell antioxidant defense and other metabolic processes via control of expression of over 200 target genes in response to various types of stress. The GSK3 system represents a “regulating valve” that controls fine oscillations in the Nrf2 level, unlike Keap1, which prevents significant changes in the Nrf2 content in the absence of oxidative stress and which is inactivated by the oxidative stress. Furthermore, GSK3 modifies core circadian clock proteins (Bmal1, Clock, Per, Cry, and Rev-erbα). Phosphorylation by GSK3 leads to the inactivation and degradation of circadian rhythm-activating proteins (Bmal1 and Clock) and vice versa to the activation and nuclear translocation of proteins suppressing circadian rhythms (Per and Rev-erbα) with the exception of Cry protein, which is likely to be implicated in the fine tuning of biological clock. Functionally, GSK3 appears to be one of the hubs in the cross-regulation of circadian rhythms and antioxidant defense. Here, we present the data on the crosstalk between the most powerful cell antioxidant mechanism, the Nrf2 system, and the biorhythm-regulating system in mammals, including the impact of GSK3 overexpression and knockout on the Nrf2 signaling. Understanding the interactions between the regulatory cascades linking homeostasis maintenance and cell response to oxidative stress will help in elucidating molecular mechanisms that underlie aging and longevity.
Over the past decades, the approaches to writing and formatting scientific articles, as well as to choosing editions by scientists for publishing the results of their research (both experimental and theoretical) have changed dramatically. Today, the majority of specialists pay much attention to formal ratings of scientific journals, since it is they that mainly determine how great the chances of the scientists published in them are to get grants for their research. And at the present stage, it is practically impossible to engage in not only applied, but also basic research without serious funding. In particular, this has become especially important for biologists and biomedical specialists working in a wide variety of fields, because they usually use expensive equipment, reagents, and experimental animals in their work. In this regard, any scientists working in the field of Life Sciences must be able to choose the appropriate journals for their publications on the basis of the scientometric indicators of the editions. No less important is the problem of formatting/designing scientific articles, because high ranked journals reject a significant percentage of manuscripts that do not meet the requirements not only after peer-reviewing but also before it (in the “rapid rejection” mode). We consider it necessary to introduce appropriate courses of lectures into the curricula of students of biological and biomedical specialties. A list of issues that are proposed to be touched in such lectures is considered, including the basics of scientometrics, work on lists of references, search for possible borrowings in manuscripts, requirements for illustrations, compliance with ethical standards, determining whether a scientific edition is a “predatory” one, peer-reviewing scientific articles, their correct structuring, etc.