Khokhlov, Alexander N

Моргунова Г.В., Хохлов А.Н.

MORGUNOVA G.V., KHOKHLOV A.N.

The search and testing of drugs with senolytic activity is one of the new directions in gerontology. The number of “senescent” cells that increases 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 a logical step to improve the quality of life and, possibly, prolong lifespan. However, drugs that have senolytic and senomorphic activity in model systems cause the development of a number of side effects in clinical trials. In this review, we consider the main advances in the field of senotherapy, the prospects for the use of senotherapy drugs, and the limitations that researchers and clinicians may encounter.

Khokhlov A.N., Morgunova G.V.

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.

Morgunova G.V., Khokhlov A.N.

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.

Khokhlov A.N.

The history of research into the basic mechanisms of the pathogenesis of Alzheimer’s disease (AD) is briefly considered. Concepts are analyzed in which a decisive role in the development of this disease was attributed to aluminum or free radicals. The lack of reliable data to date to support these concepts is emphasized. The point of view of the author is presented, according to which almost all the results indicating the feasibility of using antioxidants (as well as other potential drugs for AD) for the prevention and treatment of AD were obtained on model animals with certain pathologies (for example, with severe oxidative stress), which contribute to the formation of symptoms similar to those of AD in humans. In this regard, parallels are drawn with experimental gerontological research aimed at studying the effect of a calorie-restricted diet on aging and life span. It is noted that in these studies, animals were used that were either not completely normal or were in unfavorable conditions. According to the author, the lack of significant progress in the development of effective geroprotectors or drugs for the prevention/ treatment of AD is due to the fact that most specialists ignore the principles of classical gerontology, in particular, the definitions of aging and age-related diseases, as well as the correct approaches to the selection of control objects for their studies. It is emphasized that humans, unfortunately, cannot use the freshwater hydra method to combat aging and age-related diseases. Under certain conditions, it continuously renews all cells (including nerve ones) of its body and thereby ensures its “immortality.” In humans, the replacement of “old” neurons can lead to the loss of personality/individuality, and the “repair” of these cells today seems impossible. In this regard, the author considers it expedient to study the aging of postmitotic cells in experiments on stationary cell cultures, which can accelerate, in particular, the deciphering of the mechanisms of accumulation of beta-amyloid and senile pigments such as lipofuscin in neurons. The need for clinical studies of AD is noted as complementary to experimental work, although the first ones are much more expensive and time-consuming. Only confirmation in human studies of the effectiveness of drugs developed in experiments on model animals will allow them to be recommended for use in the clinical practice.

Khokhlov A.N.

The history of creation and the content of the elective lecture course “Basics of scientometrics and preparing scientific publications” created in 2022 at the School of Biology of Lomonosov Moscow State University are considered. The course, consisting of 12 lectures, is intended for Ph.D. students of any schools of Moscow State University, who, unlike undergraduate students, already have some experience in scientific work and publication of its results. The topics covered in the course are listed, a list of questions proposed in the test is given. Among other things, the main scientometric indicators, work on lists of references, search for possible borrowings in the manuscript, requirements for illustrations, compliance with publication ethics, determining whether a scientific publication belongs to “predatory”, reviewing scientific articles, their correct structuring, etc. are considered. Since the majority of course participants are Ph.D. students of the School of Biology of Moscow State University, special attention in the lectures is paid to the ethical issues of publishing the results of research conducted on animals and humans. It is noted that the course of lectures attracted a fairly large number of listeners interested in the correct design of their articles and choosing the best scientific editions for them. It is emphasized that these issues are especially relevant for scientists involved in the preparation of applications for grants, without which it is now almost impossible to imagine serious scientific research. The results of the test carried out after the end of the course are briefly analyzed.

Khokhlov A.N.

The history of research into the fundamental mechanisms of the pathogenesis of Alzheimer’s disease (AD) is briefly reviewed. Concepts in which a decisive role in the development of this disease was attributed to aluminum or free radicals are analyzed. The lack of reliable data to date to support these concepts is highlighted. The author’s point of view is stated, according to which almost all the results indicating the advisability of using antioxidants (as well as other potential drugs for AD) for the prevention and treatment of AD were obtained in model animals with certain pathologies (for example, with severe oxidative stress), which contribute to the formation of symptoms similar to those of AD in humans. In this regard, parallels with experimental gerontological work aimed at studying the effect of calorie-restricted nutrition on aging and life span are drawn. It is noted that these studies also used animals that were either not completely normal or were in unfavorable conditions. According to the author, the lack of serious success in the development of effective geroprotectors or drugs for the prevention/treatment of AD is due to the ignorance by most specialists of the principles of classical gerontology, in particular, the definitions of aging and age-related diseases, as well as correct approaches to the selection of control objects for their studies. It is emphasized that humans, unfortunately, cannot use the freshwater hydra method to combat aging and age-related diseases. Under certain conditions, it continuously renews all cells (including nerve cells) of its body and thereby ensures its “immortality.” In humans, replacing “old” neurons can lead to loss of personality/individuality, and “repairing” these cells seems impossible today. In this regard, the author considers it advisable to conduct studies of the aging of postmitotic cells in experiments on stationary cell cultures, which can accelerate, in particular, elucidation of the mechanisms of accumulation of beta-amyloid and senile pigments, such as lipofuscin, in neurons. The need to conduct clinical studies of AD as complementary to experimental work is noted, although the former are much more expensive and time-consuming. Only confirmation in human studies of the effectiveness of drugs developed in experiments on model animals will allow them to be recommended for clinical use.

Khokhlov A.N.

The history of the creation of the course of lectures “Basics of the Biology of Aging” at the School of Biology of Lomonosov Moscow State University, as well as at the Department of Life Science and Engineering of Harbin Institute of Technology is brie y described. In the process of teaching this course, the author got the impression that its main provisions may also be of interest to students of non-biological specialties, who have recently been quite often involved in the work on the implementation of gerontological grants. This is largely determined, apparently, by the signi cantly increased funding for this kind of research in recent years. In turn, this is a consequence of the fact that the average life span of people in developed countries has increased dramatically over the past decades. However, the maximum life span has not changed much (it is now the same as it was thousands of years ago, it is just that the chances of living to the age of a centenarian have become much greater). If earlier people often died at an early age from various diseases not related to age (mainly infectious diseases), now, due to signi cant advances in medicine, most people live to old age. As a result, death “from aging” is becoming more common. At the same time, many people have a very vague idea of what aging is, what are its mechanisms and how to ght it. In this regard, in 2022, an interschool elective course of lectures was organized at MSU for students of any departments of the university, except for the School of Biology itself. It is called “Basics of the biology of aging, or everything you wanted to know about aging (but were afraid to ask).” The material of the lectures was specially adapted for students who are not biologists by their main specialty. The main emphasis in the course, consisting of 12 lectures, is made on the fundamental de nitions and methodical/methodological approaches used in gerontology. The article lists the questions submitted for the students’ test and brie y analyzes its results.

Morgunova G.V., Shilovsky G.A., Khokhlov A.N.

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.

Khokhlov A.N.

The history of the creation of the course of lectures “Basics of the Biology of Aging” at the School of Biology of Moscow State University, as well as at the Department of Life Science and Engineering of Harbin Institute of Technology, is briefly described. In the process of teaching this course, the author got the impression that its main provisions may also be of interest to students of non-biological specialties who have recently been quite often involved in the work on the implementation of gerontological grants. This is largely determined, apparently, by the significantly increased funding for this kind of research in recent years. In turn, this is a consequence of the fact that the average life span of people in developed countries has increased dramatically over the past decades. However, the maximum life span has not changed much (it is now the same as it was thousands of years ago, it is just that the chances of living to the age of a centenarian have become much greater). If earlier people often died at an early age from various diseases not related to age (mainly infectious diseases), now, due to significant advances in medicine, most people live to old age. As a result, death “from aging” is becoming more common. At the same time, many people have a very vague idea of what aging is, what are its mechanisms and how to fight it. In this regard, in 2022, an interschool elective course of lectures was organized at MSU for students of any schools of the university, except for the School of Biology itself. It is called “Basics of the Biology of Aging or Everything You Wanted to Know about Aging (but Were Afraid to Ask).” The material of the lectures was specially adapted for students who are not biologists by their main specialty. The main emphasis in the course, consisting of 12 lectures, is made on the fundamental definitions and methodical/methodological approaches used in gerontology. The article lists the questions submitted for the students’ test and briefly analyzes its results.

Khokhlov A.N., Morgunova G.V.

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.

Khokhlov A.N.

Editor-in-Chief of Advances in Gerontology describes the current editorial policy and the strategy of future development of the renewed journal which since 2023 is published as a separate independent edition. It is emphasized that now priority is given to publications devoted to (1) the fundamental mechanisms which may determine the increase in the probability of death of living organisms, including humans, with age, and to (2) identifying various factors of both chemical and physical nature that could potentially help to slow down the aging process. In addition, papers included in Volume 13, Issue 1 are shortly reviewed.

Khokhlov A.N.

The author’s point of view is presented, according to which, formulated back in the 80s of the last century by Yu.M. Lopukhin et al., the cholesterol theory of aging and death is now often misunderstood by many biologists and physicians. It is emphasized that this theory prioritized not the well-known role of cholesterol (CS) in metabolic processes, but its structural role in the plasma membrane of the cell. It was assumed that an increase in the microviscosity of the cell membrane due to the accumulation of CS in it leads to a deterioration in the transfer of external signals and nutrients to the cell, as well as to a decrease in the activity of membrane enzymes. This, according to the authors, triggers the occurrence of “senile” changes in cells, tissues and organs, and then in the entire multicellular organism, which ultimately leds to an increase in the probability of its death, that is, to aging. At the same time, the content of CS (mainly, of considered to be especially “bad” CS of low density lipoproteins) in serum was assigned only a minor role, because its increase is not at all necessary, according to the authors of the concept, leads to adverse changes in the body. This paper briefly discusses the evolution of ideas about the possible role of CS in aging and the development of various age-related pathologies, mainly cardiovascular diseases and mental disorders. Experimental data on the effect of liposomes containing both normal and oxidized CS on the proliferative activity of cultured cells are analyzed. The data of longitudinal studies are considered, suggesting that, paradoxically, it is people with elevated levels of CS in the blood plasma who live to an advanced age. At the same time, the consumption of large amounts of food rich in CS may not affect the health of some patients. It is noted that a number of studies indicate the absence of a causal relationship between the level of CS in serum and the occurrence of atherosclerotic changes. It is emphasized that CS is a very important compound for our body, without which cell proliferation and, as a result, normal regeneration are impossible. It is noted that there is a continuously increasing amount of data on the negative role of statins in the formation of age-related pathology, especially in people of older age groups. It is concluded that at present it becomes obvious that there is a need for a significant reappraisal (using the systems approach) of ideas about the possible role of CS in aging, the development of atherosclerosis and other age-related diseases, as well as dementias due to various causes, including Alzheimer’s disease.

Khokhlov A.N.

The author’s point of view is presented, according to which the cholesterol theory of aging and death, which was formulated back in the 1980s by Yu.M. Lopukhin et al., is now often misunderstood by many biologists and physicians. It is emphasized that this theory prioritized the structural role of cholesterol in the plasma membrane of the cell rather than the well-known role of cholesterol in metabolic processes. It was assumed that an increase in the microviscosity of the cell membrane due to the accumulation of cholesterol in it leads to a deterioration in the transfer of external signals and nutrients to the cell as well as to a decrease in the activity of membrane enzymes. This, according to the authors, triggers the occurrence of “senile” changes in cells, tissues, and organs and then in the entire multicellular organism, which ultimately leads to an increase in the probability of its death, that is, to aging. At the same time, the content of cholesterol (mainly cholesterol of low-density lipoproteins, which is considered especially “bad”) in serum was assigned only a minor role, because, according to the authors of the concept, its increase does not necessary lead to adverse changes in the body. This article briefly discusses the evolution of ideas about the possible role of cholesterol in aging and the development of various age-related pathologies, mainly cardiovascular diseases and mental disorders. Experimental data on the effect of liposomes containing both normal and oxidized cholesterol on the proliferative activity of cultured cells are analyzed. The data of longitudinal studies are considered, suggesting that, paradoxically, it is people with elevated levels of cholesterol in the blood plasma who live to an advanced age. At the same time, the consumption of large amounts of cholesterol-rich food may not affect the health of some patients. It is noted that a number of studies indicate the absence of a causal relationship between the level of cholesterol in serum and the occurrence of atherosclerotic changes. It is emphasized that cholesterol is a very important compound for our body, without which cell proliferation and, as a result, normal regeneration are impossible. It is noted that there is a continuously increasing amount of data on the negative role of statins in the formation of age-related pathologies, especially in people of older age groups. It is concluded that, at present, it becomes obvious that there is a need for a significant reappraisal (using the systems approach) of ideas about the possible role of cholesterol in aging and in the development of atherosclerosis and other age-related diseases as well as dementias caused by various factors, including Alzheimer’s disease.

Morgunova G.V., Khokhlov A.N.

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.

Aswani B.S., Sajeev A., Hegde M., Mishra A., Abbas M., Vayalpurayil T., Sethi G., Kunnumakkara A.B.

Pooja, Sood S.K.

Моргунова Г.В., Хохлов А.Н.

Tiwari I., Chauhan P., Singh A., Sharma N.K.

Senescence is the markup of events related to the exit of the cell cycle by some cells due to various factors, and accumulation of such senescent cells leads to the onset of aging, but when it occurs at early stages, it becomes the cause of many age-related pathologies. Many factors can be responsible for such events, such as oxidative stress, DNA damage, telomere shortening, and overexpression of lysosomal β-gal, forming it into senescence-associated β-gal (SA-β-gal). These cells activate the apoptotic pathway involving apoptotic factors like p53-p21-16 and begin to secrete pro-inflammatory factors like chemokines and cytokines, making other adjacent cells tumorigenic, thus leading to senescence-associated secretory phenotype (SASP). In another turn of events, due to some reasons, the folding process of proteins by cytosolic chaperones or in ER gets interrupted, causing the hydrophobic amino acids to come to the surface, but such misfolded proteins further undergo ubiquitinylation and proteasomal degradation. In case misfolded proteins do not get degraded, they then aggregate and form amyloid fibrils, especially in neurons, leading to various neurodegenerative diseases such as α-synuclein in the case of Alzheimer’s and Parkinson’s. The current chapter deals with cellular senescence and various neurodegenerative disorders other than Alzheimer’s and Parkinson’s and the mechanism and techniques of their diagnosis.

Yakubets D.A., Buravkova L.B.

One of the most obvious manifestations of the negative impact of space flight factors on the human physiology is osteopenia. With the active development of manned space flights and the increase in the duration of humans' persistence in weightlessness, there is a growing need to understand the mechanisms of changes occurring at the cellular level involved in the replenishment of bone tissue. Using the RNA sequencing method, changes in the transcriptome profile of MMSCs were studied after a 5-day simulation of the microgravity effects. During the analysis, a pronounced downregulation of genes, which products are involved in processes associated with cell proliferation, in particular, in the mitotic phase of the cell cycle, was found in the experimental group of cells. These shifts in the transcriptional profile of MMSCs were confirmed using fluorescence microscopy. The results obtained indicate a decrease in the proliferative activity of MMSCs cultured under conditions of simulated microgravity for 5 days.

Ahmed B., Wang L., Hussain W., Mustafa G., Afzal M.T.

The systematic evaluation and ranking of researchers in academia stand out as a challenging and tedious task. This task facilitates policymakers in making informed decisions regarding faculty promotions, awards and providing grants by identifying deserving individuals. Researchers have put forth a range of parameters for identification of the most impactful scholars. These parameters include the count of publications and citations, along with the h-index. However, considering the associated shortcomings of the h-index, the researchers have introduced several variations of the h-index. Fictitious scenarios and datasets will be utilized to evaluate the practical and real-world effectiveness of the proposed metrics. There is a gap that requires a thorough evaluation of the specific behavior of each index. The current study emphasizes the assessment of various indices using a comprehensive dataset that includes both award-winning and non-award-winning researchers. During the evaluation of each index, the retrieval of awardees was examined within the top 10% to top 100% of the ordered list for each respective index. In addition, we investigate the correlation among several indices and awarding societies. Our findings suggest that the A-index and normalized h-index can identify over 60% of award-winning researchers.

Shilovsky G.A., Putyatina T.S., Markov A.V.

Various environmental morphological and behavioral factors may be decisive in the longevity of representatives of various taxa. Long-lived species develop systems aimed at increasing the body’s stability and defense, and ultimately increasing life expectancy. In addition, long-living species are characterized by different levels of manifestation of factors favorable to longevity (gerontological success): body size, slow metabolism, level of activity of the body’s repair systems and antioxidant defense systems, resistance to toxic substances and tumor formation, and the presence of neotenic characteristics. Continuing the work on mammals, in this work we studied the characteristics that distinguish long-lived ectotherms (crocodiles and turtles) and compared them with those of other representatives of ectotherms (squamates and amphibians) and endotherms (birds and mammals). The article also discusses mathematical indicators used to assess the predisposition to longevity in different species. These indicators include both standard ones (mortality rate, maximum lifespan, coefficient of variation of lifespan) and derivatives from them. evolutionary patterns of aging are further explained by protective phenotypes and life history strategies. The work assessed the relationship between lifespan and various studied factors, including body size and temperature, encephalization, protection of occupied econiches, the presence of protective structures (for example, shell and osteoderms), environmental temperature, etc.), and their influence on the distribution of lifespan as a statistical quantities. The hypothesis about the level of metabolism and temperature as the most determining factors of longevity was not confirmed. It turned out that animals protected by shells (turtles with their exceptional longevity) live longer than species that have poison or lack protective devices. The improvement of methods of defense against external threats in long-lived ectotherms is consistent with the characteristics of long-lived endotherms (for example, naked mole rats that live in tunnels underground, or bats and birds, whose ability to fly is also one of the best methods of defense).

Sokolov S.S., Severin F.F.

For the most of their lifespan, the probability of death for many animal species increases with age. Gompertz’s law states that this increase is exponential. In this work, we have compared previously published data on the survival kinetics of different lines of progeric mice. Visual analysis showed that in six lines of these rapidly aging mutants, the probability of death did not strictly depend on age. In contrast, ten lines of progeric mice have the survival curves similar to those of the control animals, that is, in agreement with Gompertz’s law, similar to the shape of an exponential curve upside down. Interestingly, these ten mutations cause completely different cell malfunctions. We speculate that what these mutations have in common is a reduction in the lifespan of cells and/or an acceleration of the transition to the state of cell senescence. Thus, our analysis, similar to the conclusions of many previously published works, indicates that the aging of an organism is a consequence of the aging of individual cells.

Shilovsky G.A.

The article describes the history of studies of survival data carried out at the Research Institute of Physico-Chemical Biology under the leadership of Academician V. P. Skulachev from 1970s until present, with special emphasis on the last decade. The use of accelerated failure time (AFT) model and analysis of coefficient of variation of lifespan (CVLS) in addition to the Gompertz methods of analysis, allows to assess survival curves for the presence of temporal scaling (i.e., manifestation of accelerated aging), without changing the shape of survival curve with the same coefficient of variation. A modification of the AFT model that uses temporal scaling as the null hypothesis made it possible to distinguish between the quantitative and qualitative differences in the dynamics of aging. It was also shown that it is possible to compare the data on the survival of species characterized by the survival curves of the original shape (i.e., “flat” curves without a pronounced increase in the probability of death with age typical of slowly aging species), when considering the distribution of lifespan as a statistical random variable and comparing parameters of such distribution. Thus, it was demonstrated that the higher impact of mortality caused by external factors (background mortality) in addition to the age-dependent mortality, the higher the disorder of mortality values and the greater its difference from the calculated value characteristic of developed countries (15-20%). For comparison, CVLS for the Paraguayan Ache Indians is 100% (57% if we exclude prepuberty individuals as suggested by Jones et al.). According to Skulachev, the next step is considering mortality fluctuations as a measure for the disorder of survival data. Visual evaluation of survival curves can already provide important data for subsequent analysis. Thus, Sokolov and Severin [1] found that mutations have different effects on the shape of survival curves. Type I survival curves generally retains their standard convex rectangular shape, while type II curves demonstrate a sharp increase in the mortality which makes them similar to a concave exponential curve with a stably high mortality rate. It is noteworthy that despite these differences, mutations in groups I and II are of a similar nature. They are associated (i) with “DNA metabolism” (DNA repair, transcription, and replication); (ii) protection against oxidative stress, associated with the activity of the transcription factor Nrf2, and (iii) regulation of proliferation, and (or these categories may overlap). However, these different mutations appear to produce the same result at the organismal level, namely, accelerated aging according to the Gompertz’s law. This might be explained by the fact that all these mutations, each in its own unique way, either reduce the lifespan of cells or accelerate their transition to the senescent state, which supports the concept of Skulachev on the existence of multiple pathways of aging (chronic phenoptosis).

Zheng Z., Ke L., Ye S., Shi P., Yao H.

Ruggieri E., Domenico E.D., Locatelli A.G., Isopo F., Damanti S., Lorenzo R.D., Milan E., Musco G., Rovere-Querini P., Cenci S., Vénéreau E.

Larina V.N., Shcherbina E.S.

The interaction between heart failure (HF) and osteoporosis in a multimorbid patient is a relevant complication in the aging population. The concept of inflammaging (inflammatory aging) allows us to consider the prolonged process of subclinical inflammation as an adaptation. Depending on the positive or negative influence of inflammaging on the human body, it may induce healthy longevity or aging that is accompanied by geriatric syndromes and various pathologies, including HF and osteoporosis. In this review, we aimed to highlight the issue of inflammaging as a systemic factor in the development of HF and osteoporosis. The function of inflammatory markers, the role of the NLRP3 inflammasome in the immunoinflammatory pathway, and NLRP3’s role in the development of both HF and osteoporosis via the formation of proinflammatory cytokines have been discussed. The influence on different pathogeneses have been considered to determine the development of new therapies.

Michel M., Terragno E., Bereau M., Magnin E., Gueugneau N., Soares A.V., Sagawa Y.

BackgroundMotor imagery (MI) has emerged as a promising therapeutic approach for Parkinson’s disease (PD). MI entails mentally rehearsing motor actions without executing them. This cognitive process has garnered attention due to its potential benefits in aiding motor function recovery in patients. The purpose of this review was to highlight the findings observed in motor symptoms, balance, gait, and quality of life.MethodsA literature search was carried out in Medline, Embase, Cochrane, and Physiotherapy Evidence Database (PEDro), from the first publication to February 2024. Studies with at least one keyword to PD and MI in the title were included.ResultsThe analysis included 53 studies out of the 262 identified. These comprised 12 randomized controlled trials (RCTs) with an average PEDro score of 6.6 out of 10, as well as 41 non-RCT studies. Notably, the majority of the RCTs focused on balance, gait, and lower limb exercises. The experimental group found an 85.2% improvement on the Timed Up and Go (TUG) with a cognitive task (p < 0.02), 5.8% improvement on the TUG (p < 0.05), and 5.1% improvement in walking speed (p < 0.05). Other variables did not show significant improvement. In descriptive and non-RCT studies, there were various tasks and outcomes for the lower and upper limbs. It has been demonstrated that there was no difference in execution time in MI between patients and healthy subjects (HS), whereas motor execution was slower in patients. Several tasks were analyzed for the upper limb, including thumb opposition, joystick movements, and writing tasks with variable results. RCTs were more focused on balance, lower limbs, and walking. There was no specific outcome regarding the upper limb or speech. Additionally, the heterogeneity of tasks and outcomes across studies is also a limitation.ConclusionCurrent research on walking disorders in PD shows promise, but further investigations are crucial, particularly with an emphasis on upper limb function and speech. Studies with larger sample sizes and more precise methodologies are needed to enhance our understanding of the potential benefits of MI within the framework of comprehensive PD rehabilitation.

Aksenteva M.S., Efimenko I.G., Sazhina O.S.

On February 13, 2024, the 99th anniversary of the “Great Russian Encyclopedia” (GRE) (the successor of the “Great Soviet Encyclopedia”) was celebrated. However, it was only in 2020 that work began on the scientific and educational GRE portal, which was launched in test mode on May 26, 2022 (https://bigenc.ru/). By the editorial staff of “Physical Sciences”, to date, about 2,000 articles written by outstanding physicists and selected by the representative Editorial Board have been posted on the portal. The partners of the portal are reputable scientific and educational organizations: the Russian Academy of Science (RAS), Lomonosov Moscow State University (MSU), other leading universities of the Russian Federation, and the Russian Academy of Education. The priorities of the GRE portal are reliability and accessibility. The paper presents statistics of visits to the GRE portal over the past two years. Another important electronic resource dedicated to the physical sciences and therefore analyzed jointly with the editorial board of the GRE “Physical Sciences” is the journal Uspekhi Fizicheskikh Nauk (UFN). The first issue of the UFN was published in April 1918, and the UFN website (www.ufn.ru) was opened on December 26, 1994. Since 1995, there have been statistics of visits to the UFN website, which, for the first time, allowed the UFN Editorial Board to find out how many readers it has, who they are, where they come from, what their interests and preferences are? By 2016, DOI was assigned to the entire archive of articles from the UFN in both Russian and English. By April 2024, 1075 issues of the UFN containing 11,819 articles (cited 164,216 times, data collected by DOI) written by 8,799 authors were posted on the UFN website, and 405,365,547 times visited the semantic pages of the site. Statistics of visits to the UFN website and its features in recent years will be covered in this article.The statistics of visits to the GRE Portal and the UFN website demonstrate the growing society’s request for reliable, time-tested information supported by the reputation of the editorial board and publishing houses.

Bolshakov D.Y.

The results of the research difference of the calendar date between begining and ending editorial processes in the Journal of “Almaz – Antey” Air and Space Defence Corporation are given, and the counting of dates per month for beginning the processes (entering articles, transferring to literacy editing etc.). Based on the analysis it was concluded that the incoming article might be considered as an incoming application to queuing system, which the scientific journal is. For such incoming application can be estimate the distribution functions incoming flows, average and maximum term be in queuing system, also as the distribution functions of the service mode and another characteristics, which stay unchanged (stationary) in time for researched scientific journal. 

Aksenteva M.S., Efimenko I.G., Sazhina O.S.

On February 13, 2024, the 99th anniversary of the “Great Russian Encyclopedia” (GRE) (the successor of the “Great Soviet Encyclopedia”) was celebrated. However, it was only in 2020 that work began on the scientific and educational GRE portal, which was launched in test mode on May 26, 2022 (https://bigenc.ru/). By the editorial staff of “Physical Sciences”, to date, about 2,000 articles written by outstanding physicists and selected by the representative Editorial Board have been posted on the portal. The partners of the portal are reputable scientific and educational organizations: the Russian Academy of Science (RAS), Lomonosov Moscow State University (MSU), other leading universities of the Russian Federation, and the Russian Academy of Education. The priorities of the GRE portal are reliability and accessibility. The paper presents statistics of visits to the GRE portal over the past two years. Another important electronic resource dedicated to the physical sciences and therefore analyzed jointly with the editorial board of the GRE “Physical Sciences” is the journal Uspekhi Fizicheskikh Nauk (UFN). The first issue of the UFN was published in April 1918, and the UFN website (www.ufn.ru) was opened on December 26, 1994. Since 1995, there have been statistics of visits to the UFN website, which, for the first time, allowed the UFN Editorial Board to find out how many readers it has, who they are, where they come from, what their interests and preferences are? By 2016, DOI was assigned to the entire archive of articles from the UFN in both Russian and English. By April 2024, 1075 issues of the UFN containing 11,819 articles (cited 164,216 times, data collected by DOI) written by 8,799 authors were posted on the UFN website, and 405,365,547 times visited the semantic pages of the site. Statistics of visits to the UFN website and its features in recent years will be covered in this article.The statistics of visits to the GRE Portal and the UFN website demonstrate the growing society’s request for reliable, time-tested information supported by the reputation of the editorial board and publishing houses.

Taranovskiy D.O., Stepanov O.A.

The article presents the analysis of Russian journals whose topics are related to the areas of activity of the Scientific Council on Control Theory and Processes at the Department of Energy, Mechanical Engineering, Mechanics and Control Processes of the Russian Academy of Sciences. Results of a survey of the leading Russian scientists in this field of science, including members of the council, helped to form a preliminary list of journals. The characteristics of these journals and their existing ratings are presented.It is noted that the well-known scientometric indicators do not allow one to evaluate the journals’ development pathways directly. A proposed indicator characterizes the average rate of change in a journal’s impact factor over a given time interval. The values of development indicators have been calculated and analyzed according to the Russian Index of Science Citation (RISC) and Scopus databases for the abovementioned journals included in these databases. The development pathways of some individual journals are considered.The article gives conclusions and recommendations that may be useful to the editorial staff – with a view to promoting their publications and to authors – in choosing a journal for publication. 

Moskaleva O.V., Akoev M.A.

It was investigated whether the geopolitical situation (the Russian-Ukrainian conflict) has an impact on the strategy of choosing scholarly journals by Russian authors, and what it means if it does. The data on publications of the Russian Federation from 2010 to 2023 were analyzed in comparison with other countries. The limitation of the study is a short observation period, two years, comparable to the cycle of preparation of a scientific publication. A study of the thematic focus, the author’s composition, and international cooperation was conducted. The work used data from Scopus, Web of Science, RSCI and CRIS systems. The global impact of the geopolitical situation on the publication indicators has not been revealed, although trends in international cooperation are changing in the long term. Assumptions are made about the greater impact on the number of publications of the decrease in the activity of universities of the 5-100 project, the consequences of the COVID-19 pandemic and the insufficient growth rate of new Russian authors published in Russian journals.

Spiridonova O., Kriukov D., Nemirovich-Danchenko N., Peshkin L.

Kosyakov D., Pislyakov V.

The choice to focus on a journal's impact factor, or its quartile, in authoritative rankings, when deciding where to publish research results can be driven by various reasons. These may include personal prestige, enhancing the appeal of a CV, the desire to increase publication-related rewards, meeting the conditions of scientific funds, or fulfilling qualification requirements. While these considerations deviate from the "pure science" perspective, the fact is that they are widely adopted. Our research demonstrates that the conventional division into journal quartiles may privilege certain disciplinary categories while disadvantaging others. Disciplinary categories in Journal Citation Reports (JCR) and similar rankings are imbalanced in terms of the number of articles across different journal quartiles. This is attributable to three factors: the distribution of journals across quartiles, the varying volume of journals, and the selection of the highest quartile when journals are categorized under multiple disciplines. Narrower research areas, such as Topic Clusters from SciVal, may completely lack Q1 journals dedicated to them, or even any such journals at all. This finding might also interest publishers when selecting topics for launching new titles. The apparent inequality between disciplines unveiled in our study offers a new perspective to argue against the use of quartile metrics, at least in a straightforward manner, when evaluating performance and shaping science policies.

Gureyev V.N., Kirillova O.V., Mazov N.A.

Currently, the Russian academic and publishing communities are witnesses and participants of significant changes in access to scientific information, the system of bibliometric assessment, and scientific communication. Despite some successful initiatives of the Russian academic journals, government structures for scientific and technical information, as well as commercial companies in changing one resources with others, development of new system of bibliometric evaluation and development of novel information services, it seems unreasonable to give up significant achievements of the last decades. Particularly, it is important to maintain the level of visibility and increase the quality of Russian academic journals in Web of Science Core Collection, although submission of new titles is now suspended. Due to the highest authority and wide use of this system worldwide, maintaining the proper level of visibility of the Russian journals in Web of Science database is believed to be a priority task. The paper discusses current problems concerning evaluation of representation of Russian academic serials in Journal Citation Reports and certain articles in Web of Science Core Collection in the light of lack of access to full-function versions of these databases. Updated list of Russian journals indexed in Journal Citation Reports / Web of Science as of 2023 is prepared.

Morgunova G.V., Khokhlov A.N.

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.

Morgunova G.

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.

Gille B., Muller-Eigner A., Gottschalk S., Wytrwat E., Langhammer M., Peleg S.

AbstractWild-type murine models for aging research have lifespans of several years, which results in long experimental duration and late output. Here we explore the short-lived non-inbred Titan mouse as a mouse model to test longevity interventions. We show that Titan mice exhibit increased frailty and cellular senescence at an early age. Dietary intervention attenuates the frailty progression of Titan mice. Additionally, cyclic administration of the senolytic drug Navitoclax at early age increases the lifespan and reduces cellular senescence. Our data suggests that Titan mice can serve as a cost-effective and timely model for longevity interventions in mammals.

Chelombitko M.A., Morgunova G.V., Strochkova N.Y., Lyamzaev K.G.

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.

Ilyushchenko A.K., Matchekhina L.V., Tkacheva O.N., Balashova A.V., Melnitskaia A.A., Churov A.V., Strazhesko I.D.

The aging mechanisms study is one of the most important aims in the field of geroscience and clinical medicine. There has been a wide range of fundamental research data accumulated on this matter. The processes associated with regeneration capability decrease, age-related decline of cell proliferation and resilience are highlighted in vitro studies, as well as on animal models, but their translation into clinical practice has not been carried out yet. Our aim was to study the most important mechanisms of aging and the ways of influencing on them with geroprotective technologies, such as senolytic medications. The relevance of this topic is confirmed by increasing number of launched clinical trials, but their results are often ambiguous and require further analysis and elimination of the identified difficulties and shortcomings. We have searched and analysed the literature over the past 10 years using Pubmed and Scopus, in order to find information about the main mechanisms of aging, and possible use of geroprotective medicatios in clinical practice.

Khokhlov A.N.

The history of creation and the content of the elective lecture course “Basics of scientometrics and preparing scientific publications” created in 2022 at the School of Biology of Lomonosov Moscow State University are considered. The course, consisting of 12 lectures, is intended for Ph.D. students of any schools of Moscow State University, who, unlike undergraduate students, already have some experience in scientific work and publication of its results. The topics covered in the course are listed, a list of questions proposed in the test is given. Among other things, the main scientometric indicators, work on lists of references, search for possible borrowings in the manuscript, requirements for illustrations, compliance with publication ethics, determining whether a scientific publication belongs to “predatory”, reviewing scientific articles, their correct structuring, etc. are considered. Since the majority of course participants are Ph.D. students of the School of Biology of Moscow State University, special attention in the lectures is paid to the ethical issues of publishing the results of research conducted on animals and humans. It is noted that the course of lectures attracted a fairly large number of listeners interested in the correct design of their articles and choosing the best scientific editions for them. It is emphasized that these issues are especially relevant for scientists involved in the preparation of applications for grants, without which it is now almost impossible to imagine serious scientific research. The results of the test carried out after the end of the course are briefly analyzed.

Khokhlov A.N.

The history of research into the fundamental mechanisms of the pathogenesis of Alzheimer’s disease (AD) is briefly reviewed. Concepts in which a decisive role in the development of this disease was attributed to aluminum or free radicals are analyzed. The lack of reliable data to date to support these concepts is highlighted. The author’s point of view is stated, according to which almost all the results indicating the advisability of using antioxidants (as well as other potential drugs for AD) for the prevention and treatment of AD were obtained in model animals with certain pathologies (for example, with severe oxidative stress), which contribute to the formation of symptoms similar to those of AD in humans. In this regard, parallels with experimental gerontological work aimed at studying the effect of calorie-restricted nutrition on aging and life span are drawn. It is noted that these studies also used animals that were either not completely normal or were in unfavorable conditions. According to the author, the lack of serious success in the development of effective geroprotectors or drugs for the prevention/treatment of AD is due to the ignorance by most specialists of the principles of classical gerontology, in particular, the definitions of aging and age-related diseases, as well as correct approaches to the selection of control objects for their studies. It is emphasized that humans, unfortunately, cannot use the freshwater hydra method to combat aging and age-related diseases. Under certain conditions, it continuously renews all cells (including nerve cells) of its body and thereby ensures its “immortality.” In humans, replacing “old” neurons can lead to loss of personality/individuality, and “repairing” these cells seems impossible today. In this regard, the author considers it advisable to conduct studies of the aging of postmitotic cells in experiments on stationary cell cultures, which can accelerate, in particular, elucidation of the mechanisms of accumulation of beta-amyloid and senile pigments, such as lipofuscin, in neurons. The need to conduct clinical studies of AD as complementary to experimental work is noted, although the former are much more expensive and time-consuming. Only confirmation in human studies of the effectiveness of drugs developed in experiments on model animals will allow them to be recommended for clinical use.

Bu Y., Chen S., Ruan M., Wu L., Wang H., Li N., Zhao X., Yu X., Liu Z.

Circadian disorder and high-fat diet (HFD) can disturb lipid metabolism homeostasis and may promote the development of various metabolic diseases. The relationship between them is of great concern. This study aimed to explore the effects of Per1/Per2 double knockout (DKO) on hepatic lipid metabolism in mice under HFD and HFD with docosahexaenoic acid (DHA) substitution. Both wild type (WT) and DKO male C57BL/6 mice were fed with normal chow diet (CON), HFD, or HFD with DHA substitution (AO) for 15 weeks. At the end of the experiment, mice were sacrificed at zeitgeber time (ZT) 0 (7:00 am) or ZT12 (7:00 pm). Pathological indicators were determined using histological and biochemical methods. Hepatic transcriptome sequencing analysis showed that DKO mice exhibited multiple dysfunctions in diurnal rhythm, drug metabolism, cell cycle, cancer pathways, and lipid metabolism. HFD had greater effects on fatty acid oxidation and cholesterol synthesis and metabolism in Per1-/-Per2-/- mice, which was improved by DHA substitution. Per1/Per2 played an important role in the circadian regulation of hepatic lipid metabolism, and DKO mice were more sensitive to HFD. DHA can improve circadian-related lipid metabolism disruption induced by HFD in mice.

Power H., Valtchev P., Dehghani F., Schindeler A.

AbstractSenolytics are a category of drugs that reduce the impact of cellular senescence, an effect associated with a range of chronic and age‐related diseases. Since the discovery of the first senolytics in 2015, the number of known senolytic agents has grown dramatically. This review discusses the broad categories of known senolytics—kinase inhibitors, Bcl‐2 family protein inhibitors, naturally occurring polyphenols, heat shock protein inhibitors, BET family protein inhibitors, P53 stabilizers, repurposed anti‐cancer drugs, cardiac steroids, PPAR‐alpha agonists, and antibiotics. The approaches used to screen for new senolytics are articulated including a range of methods to induce senescence, different target cell types, various senolytic assays, and markers. The choice of methods can greatly influence the outcomes of a screen, with high‐quality screens featuring robust systems, adequate controls, and extensive validation in alternate assays. Recent advances in single‐cell analysis and computational methods for senolytic identification are also discussed. There is significant potential for further drug discovery, but this will require additional research into drug targets and mechanisms of actions and their subsequent rigorous evaluation in pre‐clinical models and human trials.