Alexey Golubev

• PhD
• Researcher at N.N. Petrov Research Institute of Oncology, Saint Petersburg, Russia

To check whether the reported waves of age-dependent changes in multiomics patterns in humans influence age-specific mortality, life-table aging rate (LAR) trajectories derived from Human Morality Database (HMD) data were modeled based on assumptions inherent in a generalized Gompertz-Makeham Law (gGML). The gGML implies that any changes in resista...

Female C57BL/J mice with pulmonary fibrosis induced by injections of bleomycin (20 mg/kg intraperitoneally, 8 times for 4 weeks) were treated with a lignin derivative-based composition BP-C3 (80 mg/kg, daily intragastric administrations for 4 weeks). Bleomycin treatment increased the severity of pulmonary fibrosis (Ashcroft score increased from 1.4...

Among scarce biological relations qualifiable as laws, the Gompertz-Makeham law (GML) stands out being directly related to life-and-death issues. GML may be written as: -[dn(t)/n(t)]/dt≡µ(t) = e^(-v + γt) + C = e^(-v)*e^(gt) + C = µ0*e^(gt) + C, where µ(t) is mortality rate (MR), v captures vitality (resistance to mortality), g captures aging-assoc...

The history of studies of melatonin effects on cancer in mice is outlined, the main lesson being that the systemic in vivo effects of melatonin on animals may overwhelm the in vitro effects found using tissue explants or cell cultures. In particular, the timing of melatonin administration is of crucial importance for using the drug, which is freely...

Much attention in biogerontology is paid to the deceleration of mortality rate increase with age by the end of a species-specific lifespan, e.g. after ca. 90 years in humans. Being analyzed based on the Gompertz law µ(t)=µ0e^γt with its inbuilt linearity of the dependency of lnµ on t, this is commonly assumed to reflect the heterogeneity of populat...

Background. The creation of new experimental models carrying various heterozygous inactivating mutations in DNA repair genes and their carcinogenesis studies could expand our understanding of the spectrum of possible neoplasms that patients with such mutations are at risk of development. The aim was to study the effect of NBS1 inactivating heterozy...

The late-life mortality kinetics in several species features the deceleration of mortality rate increase with age, which in humans starts at ca. 90 years. Being analyzed based on the Gompertz law µ ( t )= µ 0 *e^ gt with its inbuilt linearity of the dependency of ln µ ( t ) on t , this feature is interpreted as reflecting the heterogeneity of a pop...

We studied the state of the DNA repair system and apoptosis in young mice carrying heterozygous inactivating mutation in the NBS1 gene (c.1971insT, p.Arg658Stop). In the peripheral blood cells of 4-month-old NBS1insT males, the %DNA in the comet tail was higher by 10% than in wild-type mice (wt) (p<0.05). In hepatocytes of NBS1insT mice, the propor...

Human lifespan is known to correlate positively with education level. In the present paper, it is explored whether there are significant differences in lifespan among those whose education may be reasonably rated as the highest possible, i.e. among scholars referred to different scientific disciplines. The publications where the lifespans of schola...

Spontaneous reactions between metabolites are often neglected in favor of emphasizing enzyme-catalyzed chemistry because spontaneous reaction rates are assumed to be insignificant under physiological conditions. However, synthetic biology and engineering efforts can raise natural metabolites' levels or introduce unnatural ones, so that previously i...

The narrative review addresses the evidence that physical activity can improve the results of prevention and treatment and of the conditions that feature increased risks of their development with aging. The main attention is paid to cancer and problems arising because of physical activity limitations associated with COVID-19 pandemic. To promote ph...

Never before in history has population aging been a driving factor in epidemics to the same extent as with the current COVID-19 pandemic, with its dramatic shift in mortality towards older age groups. The paper presents the results of an analysis of the COVID-19-related mortality data for Spain, Italy, and Sweden, which show that within the 30- to...

Introduction: The effects of chemotherapy are known to depend on the time of administration. Circadian rhythms are disturbed in tumors and in tumor bearers. Agents involved in controlling the circadian rhythms (chronobiotics) potentially can modify the outcomes of chemotherapeutics administered at different times of the day. Pineal hormone melaton...

Never before in history, aging was such a significant factor for epidemics as it is now for the current COVID-19 pandemic, which features a drastic shift of mortality towards older ages. Our analysis of data on COVID-19-related mortality in Spain, Italy, and Sweden has shown that, in the range of 30 to 90 years of age, each dependency of the logari...

When mortality (μ), aging rate (γ) and age (t) are treated according to the Gompertz model μ(t) = μ0eγt (GM), any mean age corresponds to a manifold of paired reciprocally changing μ0 and γ. Therefore, any noisiness of data used to derive GM parameters makes them negatively correlated. Besides this artifactual factor of the Strehler–Mildvan correla...

Aging can increase cancer incidence because of accumulated mutations that initiate cancer and via compromised body control of premalignant lesions development into cancer. Relative contributions of these two factors are debated. Recent evidence suggests that the latter is rate limiting. In particular, hyperglycemia caused by compromised body contro...

Survival curves were approximated and analyzed based on experimental data on the effect of different polyphenolic compounds on mouse lifespan with the Gompertz model in its minimal variant, which excludes the parameters of sample heterogeneity and age-independent mortality. Vectors from the control data towards the experimental data were plotted on...

Melatonin is subcutaneously administered in a single dose of 1.2 μg to 129/Sv mice at days 3, 5, and 7 after birth, and the mice are observed until natural death. In adult males, a decrease in the body weight and a reduction of the contribution of lung lesions detected during postmortal autopsy to mortality are detected. In adult females, an increa...

IGF1 signaling is supposedly a key lifespan determinant in metazoans. However, controversial lifespan data were obtained with different means used to modify IGF1 or its receptor (IGF1R) expression in mice. The emerging puzzle lacks pieces of evidence needed to construct a coherent picture. We add to the available evidence by using the Gompertz mode...

World Bank and Russian Federal State Statistics Service data were used to analyze cross-country correlations between life expectancy (LE) and per capita gross domestic product (GDP). The trends detected upon comparisons across different countries (the Preston curve) or regions of the Russian Federation (RF) in 2015 were compared. In addition, the c...

The chemical properties of the compounds involved in metabolic processes, even the core ones, such as glycolysis and the Krebs cycle, are not confined to the properties utilized in enzymatic reactions; they include the ability to spontaneously form covalent bonds with other compounds, including macromolecule components. The effects of the gene that...

Clock genes (C G) are responsible for adapting body to diurnal changes in environmental conditions (circadian cycles, C C) . Discordances caused by changes in both environmental CC (shift work, excess light at night, or jet lag) and bodily C C, in particular due to changes in CG expression, increase the risk of cancer, the breast being the most vul...

To analyze experimental data on the effect of various polyphenolic compounds on lifespan of mice, we approximated survival curves with the Gompertz model in its minimal form, which does not account for the heterogeneity of samples and the age-independent mortality. The plots of regressions of log0 (logarithm of the initial mortality) on  (the rat...

Parametric models for survival data help to differentiate aging from other lifespan determinants. However, such inferences suffer from small sizes of experimental animal samples and variable animals handling by different labs. We analyzed control data from a single laboratory where interventions in murine lifespan were studied over decades. The min...

Imagine that in a research field, which flourishes on funds allocated for getting an answer to a pressing question, the answer is eventually found. There will be no need to support the field any further. Specialists who sacrificed their lives to developing it will be uncompetitive in other fields, which are being developed by other scholars. That i...

Significance: The two foremost concepts of aging are the mechanistic free radical theory (FRT) of how we age and the evolutionary antagonistic pleiotropy theory (APT) of why we age. Both date from the late 1950s. The FRT holds that reactive oxygen species (ROS) are the principal contributors to the lifelong cumulative damage suffered by cells, whe...

In many cases relevant to biomedicine, a variable time, which features a certain distribution, is required for objects of interest to pass from an initial to an intermediate state, out of which they exit at random to a final state. In such cases, the distribution of variable times between exiting the initial and entering the final state must confor...

The chemical potentialities of metabolites far exceed metabolic requirements. The required potentialities are realized mostly through enzymatic catalysis. The rest are realized spontaneously through organic reactions that (i) occur wherever appropriate reactants come together, (ii) are so typical that many have proper names (e.g. Michael addition,...

Clonal cells are known to display stochastically varying interdivision times (IMT) and stochastic choices of cell fates. These features are suggested in the present paper to stem from discrete transitions of genes between different modes of their engagement in transcription. These transitions are explained by stochastic events of assembly/disassemb...

Cell interdivision periods (IDP) in homogenous cell populations vary stochastically. Another aspect of probabilistic cell behavior is randomness in cell differentiation. These features are suggested to result from competing stochastic events of assembly/disassembly of the transcription pre-initiation complex (PIC) at gene promoters. The time needed...

Natural resources transformation by economic systems into increasing human life quality and expectancy (LE) is associated with by products, including greenhouse gases, mainly CO2. When different counties are compared, LE regression on annual per capita carbon emissions (CE) is steep when annual per capita gross domestic product (GDP) is below 7000...

Several recent experiments related to fundamental aspects of cell behaviour, such as passing of the restriction point of cell cycle, which are generally interpreted in accordance with the dynamic paradigm implying the use of differential equations operating with the concentrations of cellular components and rate constants of their interactions, are...

Positively skewed distributions common in biology are often approximated with lognormal or gamma functions. It is shown here that for some classes of phenomena, including intermitotic time and protein expression variabilities, exponentially modified Gaussian (EMG) may provide better fit. EMG is generated by processes involving normally distributed...

In line with the origin of life from the chemical world, biological mortality kinetics is suggested to originate from chemical decomposition kinetics described by the Arrhenius equation k = A*exp(-E/RT). Another chemical legacy of living bodies is that, by using the appropriate properties of their constituent molecules, they incorporate all their p...

Analysis of demographic data on human mortality and lifespan carried out according to the complete Gompertz-Makeham model μ = C + λeγxt shows that, over the last 100 years, the life expectancy increased almost exclusively because the Makeham parameter C decreased. The observed changes in the demographic aging rate γ and in the initial vitality, whi...

Life on Earth has evolved from the chemical world, so nothing of chemistry has disappeared in biology even though of might become unapparent being obscured or counteracted by some other chemistry according to the biological design. Living bodies incorporate molecules involved in biological functions with all their potencies, not only those implicat...

Numerical modeling was used to explore the behavior of ideal cohorts obeying the Gompertz—Makeham (GM) law of mortality (−dn/dt· 1/n(t)=C+λeγt ) supplemented with the Strehler—Mildvan (SM) correlation (ln λ=A−Bγ) and to show how changes in the age-independent parameter C will produce an apparent SM correlation if C is ignored in mortality data trea...

Unlabelled: In telomerase-negative cell populations the mean telomere length (TL) decreases with increasing population doubling number (PD). A critically small TL is believed to stop cell proliferation at a cell-, age- and species-specific PD thus defining the Hayflick limit. However, positively skewed TL distributions are broad compared to differ...

A review of biochemical mechanisms underlying the known approaches to extension of lifespan and/or slowing down of ageing suggests that they all modify balances between generation of active oxygen and carbonyl species and the mechanisms that protect from their damaging effects or repair their consequences. A likely common target of the geroprotecto...

The age-related changes in the pineal gland are functional rather than organic, which makes their correction or prevention more tenable. The amelioration or inhibition of some age-related impairments of the pineal gland were observed with dietary restriction and the use of S-adenosylmethionine or MAO-A inhibitors. A threefold increase in nocturnal...

Telomeres are end chromosome structures, which may shorten because of DNA end replication problem and non-reparability of free-radical damage to telomeric DNA. Telomerase is an enzyme serving to maintain telomere length at a species-specific level. The absence of telomerase in somatic cells is widely believed to be the cause of the limited prolifer...

Since the discovery of enzymic fermentation by Louis Paster, the idea had been widely spread in biochemistry that all molecular interconversions and interactions in living systems are provided by the enzymes. However, recent advances in sensitivity and accuracy of analytical methods lead to isolation and identification of a variety of products that...

Analysis of recent data on telomeres and telomerases, limitations of proliferative potential of untransformed cells (Hayflick's limit), kinetics and molecular mechanism of cell proliferation and differentiation, and factors that determine the longevity of multicellular organisms suggests that: (i) chromosome end shortening during consecutive divisi...

Since the discovery of enzymic fermentation by Louis Pasteur, the idea has been widespread in biochemistry that molecular interconversions and interactions in living systems are mediated by enzymes. However, recent advances in sensitivity and separation power of analytical methods has led to isolation and identification of a variety of products tha...

Review of recent achievements in the investigation of transcription initiation mechanisms reveals that random commitment of cells to differentiation is an essential consequence of the complexity of these mechanisms. In multicellular organisms, this is not only a problem but the basis for generation of the required variety of cells.

Comparison of recent results in studies of telomeres and telomerases, limitation of the proliferative potential of untransformed cell populations ("Hayflick limit"), kinetics and molecular mechanism of cell proliferation and differentiation, and factors determining life span of multicellular organisms leads to the following conclusions: 1) chromoso...

This chapter discusses the neuroendocrine––ontogenetic model of aging and the ways of its realization. The work on the theories of aging should ultimately be aimed at the elimination of the diseases coupled with the mechanism of aging, to slowing down of the aging process, and broadening of the human lifespan. There are two tendencies in treating t...

An approach to cell proliferation and differentiation as to stochastic processes is described. The rate constants of cell population transitions to subsequent epigenetic states are interpreted as indicating instability of initial states. The duration of embryogenesis, the rate of loss of the ability to proliferation (a result of final differentiati...

The study group included 684 cases: 258 patients with breast carcinoma, 113 males with lung cancer, 42 patients with rectal tumours, 42 patients with stomach tumours, 59 patients with fibroadenomatosis, and 170 healthy subjects of varying age (male and female). A relatively high blood triglyceride level was found in patients with breast, lung, rect...