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Biomedical subjects

A G Golubev

Publications and source records attributed to A G Golubev.

17 recordsLinked to original sources

[Numerical modeling of ideal cohorts of aging organisms obeying the Gompertz-Makeham law in association with the Strehler-Mildwan correlation].

The Gompertz-Makeham law (-dn/dt x l/n(t)=C+lambdae(gammat)) so as other genuine laws of Nature is strictly applicable only to ideal objects (populations and cohorts) analogously to laws of mechanics or thermodynamics, which are exactly true only for such physical abstractions as mass points or ideal gases. Therefore, a biologically meaningful interpretation of the parameters of this law is likely to be more important for understanding the aging process than devising of alternative analytical descriptions of biodemographic processes for the sake of a better fit only. Numerical modeling of ideal cohorts of aging organisms obeying the Gompertz-Makeha law makes it possible to differentiate possible real and apparent changes in mortality patterns that occur in human history and in evolution and are observed in gerontological experiments and to demonstratively show such effects as the dependency of longevity upon population size, the evolutionarily important possibility of reciprocal changes in the mean and maximal longevity, or detection of apparent changes in negatively correlated aging rate and vitality when the Makeham term is ignored, which is usual in demography. The basic difference between the Makeham term Cand Gompertz term lambdae(gammat) is suggested to be not that the former is constant, whereas the latter is age-dependent, but that the former comprises the contributions of inherently irresistible stresses to mortality, whereas the latter comprises the contributions of resistible stresses to mortality and shows how changes in the ability to resist them is translated into changes in mortality.

Aging↗

[Understanding aging].

The essay reviews specific features of medical, biological, and biotechnological approaches to studying and understanding of biological phenomena exemplified with aging.

Aged↗

[Biochemistry of lifespan extension].

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 geroprotector effects of antioxidants, melatonin, and antidiabetic biguanides is the mitochondrial respiratory chain. In biological species that evolved through r-selection (nematodes, fruit flies, mice, and rats), the balance between anabolic/reproductive and self-maintenance/protective functions is the most significant modifiable factor of longevity and ageing. At the molecular level, the pivot of this balance is formed by the forkhead-type transfactors, whereas at the physiological level the balance is determined by dietary calories and physical activity via mechanism in which the central role is played by insuline-like peptides and, also, growth hormone and leptin or their functional analogs. In biological species that evolved through K-selection (higher primates, particularly humans), the latter balance is less important, and the biochemical factors of aging are more refracted through the higher regulatory systems, of which the most significant are catecholaminergic mechanisms of regulation of neuroendocrine-immune interrelationships and the circulatory system. This results in a decreased geroprotector potential of calory restriction and in an increased importance of the optimal physical activity. When these conclusions are compared with demographic data, it comes out that virtually all advances in gerontology may be reduced to maxims of healthy ageing known from extreme antiquity. Under optimal socioeconomic conditions, the chances to approach the documented world record of human longevity (122 years) may be increased by (not to mention getting rid of smoking and other abuses) high physical activity, adequate nutrition enriched in fresh fruits, optimism, and timely treatment of specific diseases. The most important bottleneck in the realization of these reserves is currently the public consciousness rather than the science.

Aging↗

[Aging of the pineal gland].

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 melatonin peaks occurs in old rhesus monkeys treated with a synthetic peptide Ala-Glu-Asp-Gly (Epithalon) designed basing on the amino acid content of a pineal peptide extract Epithalamin. Other effects of Epithalon markedly overlap with melatonin effects. Besides life extension in mice and fruit flies, Epithalon effects include the postponing vision loss in Campbell rats with hereditary pigmental dystrophy. A uniting aspect of such a range of activities might be the participation of transcription factors, since they are often highly conservative in evolution and, on the other hand, may be strictly tissue-specific. The targets of Epithalon may include transfactors that in mammals are specific for the pineal gland and retina and exhibit impaired functions in the aged pineal gland.

Aging↗

[The natural history of telomeres].

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 proliferative potential of somatic cells achieved when telomere length, which diminishes over successive cell generations, becomes critically short. However, telomeres are known to be highly heterogenous with regard to their length even in cloned cell populations. In this review data on telomer length distribution and changes in characteristics of these distributions observed over time are considered along with hypotheses about the nature of these phenomena. The following conclusions are drawn: causes of the known features of telomere length distribution are not limited to mere scattering and measurement error, and so any concepts concerning the relationships between telomere length and cell fate should take characteristics of telomere heterogeneity in consideration; the ratio of the initial telomere length and the rate of telomere shortening does not determine the proliferative potential of non-transformed cell populations and does not limit the lifespans of multicellular organisms; telomerase functions in non-germinal cells are either unnecessary or unknown; telomere heterogeneity may result from the stochastic nature of events committing cells to terminal differentiation and/or the loss of cell capacity to proliferate.

Aging↗

[The other side of metabolism].

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 cannot be mapped to a specific biochemical pathway. These products appear in the organism because the chemical characteristics of biomolecules are not limited to the needs of living systems realized through enzyme-catalyzed processes. This review for the first time attempts to summarize such nonenzymic interactions: (i) products of biogenic amine adduct formation to carbonyl-containing compounds in Pictet-Spengler reaction (endogenous neurotoxins which alter mitochondrial functions thus evidently participating in development of age-related cerebral aberrations, i.e., parkinsonism); (ii) products of Schiff base formation with subsequent Amadori rearrangement (nonenzymic glycation of proteins involved in age-related diabetic disorders and atherosclerosis); (iii) products of Michael addition of methylglyoxal, 4-hydroxynonenal, and other products of nonenzymic conversions of carbohydrates and lipids; (iv) products of biomolecule modification with nitrogen- and oxygen-derived free radicals which contribute to cancer and aging. Some applications of these problems in evolutionary and medical biology are reviewed.

Animals↗

[Biochemistry of space and time (telomeres, telomerases, and longevity of cell populations and multicellular organisms].

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 divisions of cells that lack telomerase limits cell proliferation beyond Hayflick's limit; (ii) Hayflick's limit can be a manifestation of mechanisms that determine the size of the living organism (it correlates with longevity) but not the longevity of multicellular organisms.

Animals↗

[A rotational floating viscosimeter for hemorheological studies].

The authors describe a modified Zimm-Krothers viscosimeter fit for hemorheological studies. The device is easy to make; it permits work within the range of shear rates from 1 to 100 sec-1 using but 1.5 ml of blood, plasma, or red cell suspension. The error of a single measurement is under 5 percent.

Blood Viscosity↗

[Carcinogenesis, embryogenesis and aging from the view point of the assessment of cell proliferation and differentiation as a stochastic process].

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 differentiation) by the initial cell cultures, the error accumulation rate in the genetic cell apparatus (including both the genome itself and its interactions with the chromatin components) which determines the rate of ageing and the rate of the tumour incidence rise in particular, are all connected via the level of instability of the epigenetic states of cells. It is supposed that the differentiation mechanism of multicellular organisms originated from mechanisms of intragenome recombinational rearrangements of unicellular ones. A hypothetic scheme for basic processes occurring during cell differentiation is proposed accounting for the dual character of oncogenes necessary for differentiation but able to block it under definite conditions.

Aging↗

Peculiarities of hyperlipidaemia in tumour patients.

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, rectal (females), and stomach (female) tumours. The blood concentration of high-density lipoprotein-cholesterol in patients with breast, lung, and stomach (female) tumours was relatively low. The elimination of tumour (breast carcinoma) did not lead to significant changes in lipid metabolism. There was no correlation between degree of lipidaemia and stage of tumour progression except in the cases of rectal cancer. Preliminary results are presented on the tentative classification of hyperlipoproteinaemia in tumour patients, using the lipid concentration threshold values advocated by Carlson et al. (1977); an increased frequency of Type IV hyperlipoproteinaemia proved to be the most characteristic feature of tumour patients. The results are discussed in terms of the concept of the importance of lipid metabolic disturbances, primarily those due to ageing, in the genesis of the syndrome of "cancerophilia" (predisposition to cancer).

Adult↗

[Change in the activity of NAD- and NADP-specific malate dehyrdogenases in oxygen deficiency in different tissues].

NAD-dependent malate dehydrogenase (1.1.1.37) activity was markedly decreased under hypoxia in rat brain and liver mitochondria and cytoplasm; most significant decrease was observed in brain cortex mitochondria. NADP-dependent malate dehydrogenase (1.1.1.40) activity was also reduced under these conditions and the most considerable changes were found in liver mitochondria and cytoplasm. Distribution of activities of these enzymes between subcellular fractions of brain and liver did not change under hypoxia. The oxaloacetate level rised by 20% in brain and decreased by 20-25% in liver under hypoxia.

Animals↗