Ekaterina Mironova

Maintaining healthy longevity requires slowing down age-related changes and supporting the body's ability to recover function after stress. With age, the adaptive response becomes increasingly compromised: inflammation and metabolic mobilization persist, the reserve decreases, and allostatic load accumulates. This article reviews data on age-related changes through the concept of the redox code — the spatiotemporal organization of electron transfer, reduction fluxes, and reversible protein modifications. This approach enables us to correlate molecular mechanisms of aging with the disruption of effective feedback loops, mitochondrial maintenance, and cellular turnover. Based on advances in redox biology and the results of studying precursor drugs, we proposed a concept of the pharmacological modulation of the redox code in the context of adaptive response development — signal perception, matching needs with resources, and timely restoration of regulatory circuits. The proposed approach has been shown to complement risk mitigation, physical adaptation, interference with cellular renewal, and epigenetic reprogramming. Organ-specific ageotypes and the circadian phases determine the individual context of modulation. This approach distinguishes the reductive capacity as an independent level of healthy longevity pharmacology. Its practical results include the completion of adaptation, decreased residual chronic stress, and preserving readiness for subsequent impacts.

Redox (reduction–oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H₂O₂), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli—from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a “generator” of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization—from subcellular to systemic—are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms—from molecular and cellular to tissue, organ, and organismal levels—with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis.

Cognitive disorders present significant medical and social challenges nowadays, due to their high prevalence, progressive course and a lack of effective methods for treatment of neurodegenerative diseases and comorbid pathologies. An important area of research is the identification of molecular biomarkers that reflect early pathophysiological changes and facilitate a more accurate biological characterization of cognitive impairment. This study provides an overview of the most relevant signaling molecules for diagnosing cognitive disorders. It presents data on the effectiveness of using comprehensive panels of molecular biomarkers in clinical practice, including β-amyloid, CD34, claudin, DRP1, endothelin-1, NF-kB, PINK1, RAGE, S100, α-synuclein, and tau protein, in patients with Alzheimer’s disease (AD) and vascular dementia (VD). The study results demonstrate that cumulative changes in the expression of signaling molecules reflect various neurodegenerative and vascular-associated biological processes. The data obtained are comparative in nature and require further validation before potential clinical application.

Redox (reduction-oxidation) processes underlie all forms of life and are a universal regulatory mechanism that maintains homeostasis and adapts the organism to changes in the internal and external environments. From capturing solar energy in photosynthesis and oxygen generation to fine-tuning cellular metabolism, redox reactions are key determinants of life activity. Proteins containing sulfur- and selenium-containing amino acid residues play a crucial role in redox regulation. Their reversible oxidation by physiological oxidants, such as hydrogen peroxide (H₂O₂), plays the role of molecular switches that control enzymatic activity, protein structure, and signaling cascades. This enables rapid and flexible cellular responses to a wide range of stimuli—from growth factors and nutrient signals to toxins and stressors. Mitochondria, the main energy organelles and also the major sources of reactive oxygen species (ROS), play a special role in redox balance. On the one hand, mitochondrial ROS function as signaling molecules, regulating cellular processes, including proliferation, apoptosis, and immune response, while, on the other hand, their excessive accumulation leads to oxidative stress, damage to biomolecules, and the development of pathological processes. So, mitochondria act not only as a "generator" of redox signals but also as a central link in maintaining cellular and systemic redox homeostasis. Redox signaling forms a multi-layered cybernetic system, which includes signal perception, activation of signaling pathways, the initiation of physiological responses, and feedback regulatory mechanisms. At the molecular level, this is manifested by changes in the activity of redox-regulated proteins of which the redox proteome consists, thereby affecting the epigenetic landscape and gene expression. Physiological processes at all levels of biological organization—from subcellular to systemic—are controlled by redox mechanisms. Studying these processes opens a way to understanding the universal principles of life activity and identifying the biochemical mechanisms whose disruption causes the occurrence and development of pathological reactions. It is important to emphasize that new approaches to redox balance modulation are now actively developed, ranging from antioxidant therapy and targeted intervention on mitochondria to pharmacological and nutraceutical regulation of signaling pathways. This article analyzes the pivotal role of redox balance and its regulation at various levels of living organisms—from molecular and cellular to tissue, organ, and organismal levels—with a special emphasis on the role of mitochondria and modern strategies for influencing redox homeostasis.

Cognitive disorders present significant medical and social challenges nowadays, due to their high prevalence, progressive course and a lack of effective methods for treatment of neurodegenerative diseases and comorbid pathologies. An important path for solving this problem is the search for reliable biomarkers that allow for early and differential diagnosis, especially in view of the similarity between clinical manifestations of different forms of dementia. This study provides an overview of the most relevant signaling molecules for diagnosing cognitive disorders. It presents data on the effectiveness of using comprehensive panels of molecular biomarkers in clinical practice, including β-amyloid, CD34, claudin, DRP1, endothelin-1, NF-kB, PINK1, RAGE, S100, α-synuclein, and tau protein, in patients with Alzheimer's disease (AD) and vascular dementia (VD). The study results demonstrate a high diagnostic relevance of the combined use of signaling molecules as a biomarker panel for screening and differentiating neurodegenerative diseases.

Cognitive impairment screening is an important issue in modern biomedicine. Neuropsychological tests have their limitations and, in some cases, fail to ensure an objective assessment of the dementia presence in individuals, especially in early stages of the disease development. In this study, we have investigated the expression of signaling molecules in the buccal epithelium, which are involved in the biochemical mechanisms of cognitive impairment caused by neurovascular pathology, in order to develop a diagnostic panel of molecular markers for dementia. Buccal epithelial samples from 146 participants, including 100 patients with vascular dementia (VD) and 46 healthy volunteers, were analyzed using immunocytochemistry. Based on the obtained results, a diagnostic panel for vascular dementia screening was developed, including such markers as β-amyloid, NF-κB, tau protein, claudin, and S100 protein. The buccal epithelium has been found to provide a convenient source of biomaterial for non-invasive diagnosis of cognitive disorders caused by neurovascular pathologies.

Sirtuins (SIRT1–SIRT7) are NAD⁺-dependent deacetylases that link cellular energy status to chromatin maintenance, mitochondrial function and inflammatory signaling. While modulation of SIRT1, SIRT3 and SIRT6 extends lifespan in model organisms, evidence in extreme-age humans is scarce. We quantified protein and mRNA levels, and protein-to-mRNA ratios for SIRT1, SIRT3 and SIRT6 in buccal epithelial cells obtained from healthy young adults, middle/late-aged individuals and nonagenarians/centenarians residing in a longevity-enriched region of south-eastern Azerbaijan. The cohort comprised 23 participants, stratified by sex and cardiovascular disease (CVD) status (5 per sex/CVD subgroup). This design allows us to: (1) define a baseline “sirtuin profile” of healthy longevity, (2) evaluate the impact of CVD as a prevalent age-related pathology, and (3) explore potential sex-specific modulation. These findings establish an initial human framework linking sirtuin translational control to healthy ageing and cardiovascular health.

Онкологические заболевания стабильно занимают позицию наиболее распространенных в мире с высокой смертностью. Неэффективность применяемых средств лекарственной терапии обусловлена множественной лекарственной устойчивостью (МЛУ) — способностью злокачественных клеток сохранять жизнеспособность в ответ на воздействие химиотерапии. Многие исследования доказывают, что важную роль в прогрессировании опухоли и развитии МЛУ играет кальций-связывающий белок сорцин, способный регулировать многие опухолевые процессы. Сорцин сверхэкспрессируется в раковых клетках и способствует их выживаемости. Снижение экспрессии сорцина может привести к усилению химиотерапевтического эффекта при воздействии на опухоль. В связи с этим актуален поиск регуляторов, лигандов сорцина, в частности малых молекул, среди которых можно выделить дигидромирицетин, ондансетрон, тетрандрин, PH II-7, кальцитриол, триптолид и др. Таким образом, сорцин является потенциальной молекулой-мишенью для разработки новых методов, направленных на диагностику и таргетную терапию онкологических заболеваний. В обзоре рассмотрены структура и функции сорцина, его роль в развитии лекарственной устойчивости и онкогенезе, а также потенциальные регуляторы — малые молекулы, ингибирующие экспрессию сорцина.

Research in the field of mitochondrial biomarkers plays an important role in understanding the processes of cellular aging. Mitochondria are not only the energy centers of the cell, but also key regulators of signaling within the cell. They significantly affect the life and function of the cell. The aging process of cells is associated with various factors, including DNA damage, disruption of the cell cycle, changes in mitochondria, and problems with signal transmission. Mitochondrial dysfunction is a major contributor to cellular and organismal aging. As we age, there is an accumulation of dysfunctional mitochondria, leading to decreased efficiency of oxidative phosphorylation and increased production of reactive oxygen species. This review focuses on the main mitochondrial markers involved in the mechanisms of cell aging: DRP1, Prohibitin, Parkin, PINK1, MFF, VDAC, TOM. These signaling molecules are involved in mitochondrial fission and the mechanisms of mitochondria-dependent apoptosis, in the regulation of mitochondrial respiratory activity, ensuring the stability of the organization and copying of mitochondrial DNA, protecting cells from oxidative stress, in the process of autophagy of damaged mitochondria, in protective mechanisms during stress-induced mitochondrial dysfunction. Analysis of mitochondrial markers can provide valuable information about the state of cells and their functional significance at various stages of aging, which could promote our understanding of cellular aging mechanisms and developing corrective methods. These insights highlight mitochondrial proteins as potential therapeutic targets to combat age-related diseases.

Alzheimer's disease (AD) remains one of the most significant medical and social problems nowadays, which is due to its high prevalence, progressive course and a lack of effective treatment methods. The most important path for solving this issue is the search for reliable biomarkers which allow for the early and differential diagnosis of AD, especially in the context of similarity of its clinical manifestations to other forms of dementia, such as vascular dementia, for example. This study provides a comparative analysis of the expression of certain biomarkers involved in the neurodegeneration such as β-amyloid, CD34, claudin, DRP1, endothelin-1, NF-kB, PINK1, RAGE, S100, α-synuclein, and tau protein in buccal epithelium samples from patients with AD, vascular dementia, and from healthy persons. The obtained results made it possible to form a panel of molecular markers, including α-synuclein, RAGE, PINK1, and phosphorylated tau protein for the differential diagnosis of AD.