Vol 9, No 2 (2019)

Standard survival analysis involves consideration of the proportion of live individuals in the cohort at a specific time point. We propose to analyze the dependence of survival variance on cohort age. This approach allowed us to identify several age periods in the ontogenesis of Drosophila melanogaster. The first two are approximated by an exponential equation, and the later ones are approximated by a sigmoid curve. The parameters of these curves can be changed under short-term (11 days) and long-term (22 days) exposure to low temperature, as well as with the addition of Cytoflavin to the nutrient medium. The proposed approach, in our opinion, makes it possible to search for “age-associated” geroprotective effects.

The goal of the work is a comparative study of the effect of constant illumination depending on the time of onset of exposure (from one month to 14 months of age) on the development of a number of oncological and age-related diseases in male rats. The results of the study show that a decrease in the functional activity of the pineal gland under the influence of constant illumination from one month of age increases the incidence of inflammatory, nontumor, and tumor genesis and leads to the rapid development of age-related pathology. Conversely, rat maintenance in constant light mode from 14 months of age slows the development of age-related pathology and reduces the incidence and development of malignant tumors.

The review analyzes the results of modern studies that involve gene therapy methods for the correction of neurodegenerative diseases. Approaches based on gene-editing technologies and their prospective use in medicine are considered. There may be limitations to the use of the genome-editing tools in the treatment of these pathologies due to features of the pathogenesis of neurodegenerative diseases.

In research on the pathogenetic patterns of Parkinson’s disease, it is important to adequately assess the mechanisms of age-related involution and morphological changes that form in the brain during this process. The clinical symptoms detected in Parkinson’s disease (rigidity, hypokinesia, tremor) indicate the involvement of nigrostriatal brain structures in the pathological process due to the death of dopamine neurons in the compact part of the substantia nigra. At the same time, a loss of these neurons, as well as a change in the number of neuroglia cells in the substantia nigra of the brain, are detected not only in Parkinson’s disease but also in physiological aging. This review presents and compares data on the morphological changes in the compact part of the substantia nigra of the human brain in normal aging and Parkinson’s disease.

Metabolism disorders of L-kynurenine, which is an intermediate product of the decomposition of genetically encoded L-tryptophan amino acid, is a component in the development of a number of neuropathological processes. The effect of tryptophan and kynurenine on cell proliferation has been studied in the organotypic culture of cerebral cortex tissue in young and old rats. Tryptophan at an effective concentration (0.05 ng/mL) oppressed cell proliferation in the cerebral cortex in young and old rats by 35 and 18%, respectively. However, cell proliferation was stimulated under the action of kynurenine (1 ng/mL), and it was more pronounced in cerebral cortex explants in old rats (by 22% as compared with the control group). The obtained data on kynurenine properties for the stimulation of cell proliferation in the cerebral cortex in old animals is promising for the creation of new medicinal nootropic drugs in age-associated diseases of the nervous system.

This review examines the basic theories of aging, which show the irreversibility of this process that leads to the death of cells and the body. The hypotheses of phenoptosis and apoptosis are discussed, as well as the view that disadaptation initiates free radical oxidation reactions and violates the neurohumoral regulation of functions. The review briefly examines the mechanisms of the development of age-related diseases. The hypothesis that partial adaptation and disadaptation are transitional biological processes associated with aging is proposed. A regularity that manifests itself in a reduction of the functional activity of an organ and cell metabolism in the state of disadaptation and aging (the principle of the limitation of cellular metabolism) is described. The study shows that aging leads to the progression of homeostatic disorders and changes in DNA methylation processes. The problem of the use of antioxidants, endogenous peptides, telomerase, and ozone to prevent the negative effects of oxidative stress on biomolecules and cellular structures is considered. It was proposed that the biosynthesis of biogenic amines significantly decreases during disadaptation and aging, which entails a decrease in the regulatory control of biochemical reactions by the hypothalamic-pituitary system. It is proposed that biogenic amines and their derivatives be considered substances that minimize the dysregulatory processes that reduce disadaptive manifestations in the body, stimulate cellular metabolism, and slow the aging process.

The interspecies differences in the mean lifespan and the composition of transposon sequences, the tissue- and stage-specific activation of which plays a role in the management of the cell differentiation process, allows the assumption that the regular processes that underlie aging are determined by the dysfunction of species-specific mobile elements. The presented literature data confirm this assumption and the key role of transposons in the regulation of gene expression during ontogenesis. The silencing mechanisms of mobile elements (which are depleted) are activated in terminally differentiated cells. This leads to dysfunction of the gene regulatory networks controlled by transposons, aging, and the development of age-associated pathologies. Transposons are capable of translocating into strictly defined loci of the genome, where they are transcribed into functional RNAs that are translated into peptides. It is assumed that the identification of activity changes associated with the aging of specific mobile elements via analysis of the noncoding RNA of transposon origin may be the basis for the development of ways to increase life expectancy and for targeted therapy of age-associated pathologies, including malignant neoplasms. In this regard, the study of peptides that affect the expression of specific transposons and noncoding RNAs may be a promising direction.

The pineal gland (PG), or epiphysis, is involved in the organization of biological rhythms and adaptive reactions of the organism by the hormone melatonin. It is shown that various factors can influence the morphology and functional activity of the gland. Calcified concretions (corpora arenacea, brain sand) are unique biomineral structures of the PG; the causes of their formation and their possible functional significance have been unclear until now. To date, concrements have been found in four species of birds and 21 mammalian species, as well as in humans; they are absent in fish, amphibians, and reptiles. In this review, we have collected the available literature data on the composition, mechanisms of formation, and possible factors affecting the accumulation of concretions in the epiphysis. Although the generally accepted point of view is that the accumulation of pineal calcium deposits is age-dependent, the available data on PG mineralization lead to the conclusion that there is most likely a multifactorial mechanism of concrement formation. In addition, the nature and crystallinity of the inorganic tissue of the pineal concretions suggest that corpora arenacea, is a regulated and physiological type of petrification rather than a pathological type. The existence of contradictory data on the connection between the formation of brain sand and the change in the functional activity of the PG during seasonal endocrine changes and in the aging process requires the study of deposits and in-depth investigation.

Sympathetic innervation of the stomach is carried out by the prevertebral ganglia of the solar plexus. The localization and neurochemical composition of neurons innervating the stomach in the postnatal ontogenesis of rats have been studied by the method of retrograde axon transport of Fast Blue. In all animals, the celiac ganglia had more labeled neurons than the superior mesenteric ganglion. The number of labeled neurons increased in the first ten days of life and then did not change until senescence. All labeled neurons innervating the stomach contain tyrosine hydroxylase, the catecholamine synthesis enzyme. The proportion of labeled neuropeptide Y-immunopositive neurons did not change during ontogeny; the percentage of labeled calbindin-immunoreactive neurons decreased in the first month of life.

Cardiovascular diseases caused by atherosclerosis are one of the most important social and economic problems in many countries of the world due to the high morbidity and mortality rate of the working population. An immunological theory of atherosclerosis and coronary heart disease (CHD) has been actively developed of late, and markers of inflammation characterizing immuno- and atherogenesis have been sought. The buccal epithelium (BE) can be used as biological material for in vivo molecular-cellular studies, allowing CHD diagnosis via inflammation markers. The purpose of the work was a comparative study of the expression of IL-1β, IL-6, IL-10, MCP-1, and GDF-15 in BE in patients of different ages with CHD and without cardiovascular disease. The BE material in healthy donors and patients with second-stage CHD was divided into groups according to the age classification of the WHO: the first group included middle-aged people (45–59 years), and the second included elderly people (60–74 years). Control material was obtained from people of middle and old age without cardiovascular disease. According to the immunocytochemical study, the area of IL-1β expression in BE is three times higher in middle-aged CHD patients and 4.4 times higher in elderly people as compared to healthy individuals of the same age group. The area of IL-6 expression in middle-aged and elderly CHD patients was 7.9 and 7.4 times higher, respectively, than in the control group. In middle-aged and elderly CHD patients, the IL-10 expression was 1.6 and 2.8 times higher, respectively, as compared to healthy donors of the same age group. The MCP-1 expression in the BE of middle-aged and elderly people with and without ischemic heart disease did not differ. GDF-15 expression is 6.8 and 6.6 times higher in middle-aged and elderly CHD patients than in healthy people of the same age. The findings showed that the expression of the cytokines IL-1β, IL-6, IL-10, and GDF-15 increase in the BE of patients with CHD in middle-aged and elderly people as compared with persons of the same age group without cardiovascular disease. Thus, the BE can serve as an informative material for noninvasive molecular diagnosis of CHD in people of different ages.