Role of the mtDNA Mutations and Mitophagy in Inflammaging

Ageing is an unavoidable multi-factorial process, characterised by a gradual decrease in physiological functionality and increasing vulnerability of the organism to environmental factors and pathogens, ending, eventually, in death. One of the most elaborated ageing theories implies a direct connection between ROS-mediated mtDNA damage and mutations. In this review, we focus on the role of mitochondrial metabolism, mitochondria generated ROS, mitochondrial dynamics and mitophagy in normal ageing and pathological conditions, such as inflammation. Also, a chronic form of inflammation, which could change the long-term status of the immune system in an age-dependent way, is discussed. Finally, the role of inflammaging in the most common neurodegenerative diseases, such as Alzheimer’s and Parkinson’s, is also discussed

The Role of KLF2 in the Regulation of Atherosclerosis Development and Potential Use of KLF2-Targeted Therapy

Kruppel like factor 2 (KLF2) is a mechanosensitive transcription factor participating in the regulation of vascular endothelial cells metabolism. Activating KLF2 in endothelial cells induces eNOS (endothelial nitric oxide synthase) expression, subsequent NO (nitric oxide) release, and vasodilatory effect. In addition, many KLF2-regulated genes participate in the anti-thrombotic, antioxidant, and anti-inflammatory activities, thereby preventing atherosclerosis development and progression. In this review, we summarise recent evidence suggesting that KLF2 plays a major role in regulating atheroprotective effects in endothelial cells. We also discuss several recently identified repurposed drugs and natural plant-based bioactive compounds with KLF2-mediated atheroprotective activities. Herein, we present a comprehensive overview of the role of KLF2 in atherosclerosis and as a pharmacological target for different drugs and natural compounds and highlight the potential application of these phytochemicals for the treatment of atherosclerosis

Heat Shock Protein 90 as Therapeutic Target for CVDs and Heart Ageing

Cardiovascular diseases (CVDs) are the leading cause of death globally, representing approximately 32% of all deaths worldwide. Molecular chaperones are involved in heart protection against stresses and age-mediated accumulation of toxic misfolded proteins by regulation of the protein synthesis/degradation balance and refolding of misfolded proteins, thus supporting the high metabolic demand of the heart cells. Heat shock protein 90 (HSP90) is one of the main cardioprotective chaperones, represented by cytosolic HSP90a and HSP90b, mitochondrial TRAP1 and ER-localised Grp94 isoforms. Currently, the main way to study the functional role of HSPs is the application of HSP inhibitors, which could have a different way of action. In this review, we discussed the recently investigated role of HSP90 proteins in cardioprotection, atherosclerosis, CVDs development and the involvements of HSP90 clients in the activation of different molecular pathways and signalling mechanisms, related to heart ageing

Role of Impaired Mitochondrial Dynamics Processes in the Pathogenesis of Alzheimer’s Disease

Mitochondrial dysfunction is now recognized as a contributing factor to neurodegenerative diseases, including Alzheimer’s disease (AD). Mitochondria are signaling organelles with a variety of functions ranging from energy production to the regulation of cellular metabolism, energy homeostasis, and response to stress. The successful functioning of these complex processes is critically dependent on the accuracy of mitochondrial dynamics, which includes the ability of mitochondria to change shape and position in the cell, which is necessary to maintain proper function and quality control, especially in polarized cells such as neurons. There has been much evidence to suggest that the disruption of mitochondrial dynamics may play a critical role in the pathogenesis of AD. This review highlights aspects of altered mitochondrial dynamics in AD that may contribute to the etiology of this debilitating condition. We also discuss therapeutic strategies to improve mitochondrial dynamics and function that may provide an alternative treatment approach

State-selective spectroscopy of water up to its first dissociation limit

A joint experimental and first-principles quantum chemical study of the vibration-rotation states of the water molecule up to its first dissociation limit is presented. Triple-resonance, quantum state selective spectroscopy is used to probe the entire ladder of water’s stretching vibrations up to 19 quanta of OH stretch, the last stretching state below dissociation. A new ground state potential energy surface of water is calculated using a large basis set and an all-electron, multireference configuration interaction procedure which is augmented by relativistic corrections and fitted to a flexible functional form appropriate for a dissociating system. Variational nuclear motion calculations on this surface are used to give vibrational assignments. A total of 44 new vibrational states and 366 rotation-vibration energy levels are characterized; these span the region from 35 508 to 41 126 cm-1 above the vibrational ground state

HORIZONS OF RESEARCH IN GEOGRAPHY OF THE WORLD ECONOMY

The advent of "world economic transition" and the formation of a multipolar world is closely linked, according to experts, with loss of globalization advances, which strengthens regionalism, increases diversification and fragmentation of the modern world, creating risks and threats to the world development. In this light studying the spatial organization of the global economy becomes more important, and at the same time that complicates the choice of priorities in the research activities of the Department of geography of the world economy, Faculty of Geography, Moscow State Lomonosov University in 2016-20, requiring a new research “ideology”. The article summarizes some ideas expressed by the department staff. It specifies that concept of territorial division of labor, as well as the defined set of key actors in the world economy and common assumptions regarding their contributions to its development needs a significant revision. The above firstly concerns giant developing countries, in particular rapidly growing China – a kind of locomotive entraining other developing states. Further, the impact of multinationals on the overall architecture and the territorial organization of the global economy becomes more and more tangible. This phenomenon requires the creation of a new scientific area of concern – the corporate geography as a tool to thoroughly investigate the transnational division of labor. Changes in the balance of acting forces are closely related to changes in industry composition and spatial organization of the global economy. The article raises the issues of development of such processes as tertiarization of the economy, reindustrialization and neoindustrialization, the latter being understood as an evolutionary transition to a knowledge-intensive, high-tech, mass labor-replacing and environmentally efficient industrial production. Basing on preliminary research from the standpoint of a relatively new methodological approach – formation of value chains – the vector of "geographical transition" " in their creation from developed to developing countries was designated. This means increasing complexity of the territorial structure of the world economy and an increase in the importance of semi-periphery. A spatial projection of globalization processes in the form of emerging “archipelago of cities”, which consolidates the international network of TNCs as the supporting node frame of the global economy requires close attention and analysis. The need of comprehending the study scope in the field of geography of the world economy in medium Atlas Information Systems (AIS), which in terms of functionality belong to the upper class of electronic atlases, is noted