Vol 83, No 12-13 (2018)

This is an overview of the biography and scientific accomplishments of Dr. Juri Vasiliev, an outstanding Russian cell biologist. Ju. M. Vasiliev published seminal papers on carcinogenesis and cytoskeleton of normal and cancer cells. He founded a scientific school and mentored many students that are now occupying leading positions in different laboratories throughout the world.

Recent advances in the technology of “aging clocks” based on DNA methylation suggest that it may soon be possible to measure changes in the rate of human aging over periods as short as a year or two. If this potential is realized, the testing of putative anti–aging interventions will become radically cheaper and faster. This should prompt a re–appraisal of the entire spectrum of methods for evaluating anti–aging technologies in humans and in model systems. In the body of this article, I will argue that (1) testing, not development, is the bottleneck in the flow of knowledge about human anti–aging; (2) single interventions are unlikely to afford major increments in life expectancy in humans; (3) interactions among combinations of known anti–aging interventions are the most important unknown in the field; (4) the daunting number of combinations may be tamed by enrolling large numbers of early adopters who are already using diverse combinations of strategies; (5) the newest methylation clock, called “DNAm PhenoAge” (Levine, M., et al. (2018) Aging (Albany), 10, 573–591) has the potential to tell us which of these people are best succeeding in their quest to slow the aging clock; (6) further optimization of this clock, specialized to the proposed application, is feasible; and (7) multivariate statistics can be used to efficiently identify the best combinations of known interventions that are already being deployed by members of the community which actively seeks to enhance their long–term health. The integration of these ideas leads to a proposal for a human trial crowd–funded largely by the subjects, organized around a web site, as well as standardization of individual record–keeping and an open–source database of methylation results before and after.

Capsid proteins (CPs) of (+)RNA–containing plant viruses are multifunctional proteins involved in many stages of viral infection cycle, in addition to their main function of virus capsid formation. For example, the tobamoviral CP ensures virus systemic transport in plants and defines the virus–host interactions, thereby influencing the virus host range, virus infectivity, pathogenicity, and manifestation of infection symptoms. Hordeiviruses and tobamoviruses belong to the Virgaviridae family and have rod–shaped virions with a helical symmetry; their CPs are similar in structure. However, no non–structural functions of hordeiviral CPs have been described so far. In this study, we assayed possible non–structural functions of CP from the barley stripe mosaic virus (BSMV) (hordeivirus). To do this, the genome of turnip vein clearing virus (TVCV) (tobamovirus) was modified by substituting the TVCV CP gene with the BSMV CP gene or its mutants. We found that BSMV CP efficiently replaced TVCV CP at all stages of viral infection. In particular, BSMV CP performed the role of tobamoviral CP in the long–distance transport of the chimeric virus, acted as a hypersensitive response elicitor, and served as a pathogenicity determinant that influenced the symptoms of the viral infection. The chimeric tobamovirus coding for the C–terminally truncated BSMV CP displayed an increased infectivity and was transported in plants in a form of atypical virions (ribonucleoprotein complexes).

Atherosclerosis underlies the development of many cardiovascular diseases that continue to hold a leading place among the causes of death in developed countries. The role of activated immune cells in atherosclerosis progression has been convincingly demonstrated, but the mechanism of their action remains poorly investigated. Since atherosclerosis is associated with chronic inflammatory response, involvement of viral and bacterial infections in atherogenesis has been examined. A special place among the infectious agents is held by human herpesviruses as the most common persistent viruses in human population coupled to chronic inflammation during atherosclerosis. We found that activation of cytomegalovirus (CMV, human herpesvirus 5) infection is associated with the emergence of acute coronary syndrome, which is in a good agreement with the data on productive CMV infection published elsewhere. In this review, we discuss the data obtained by us and other researchers regarding the role of cytomegalovirus infection and related potential mechanisms resulting in the expansion of atherosclerotic plaques during ischemic heart disease and stroke, including virus transfer to immune and endothelial cells via extracellular vesicles. In particular, the data presented in the review demonstrate that virus spreading in the vascular wall triggers immune system activation in atherosclerotic plaques and causes endothelial dysfunction. Moreover, productive CMV infection in patients with acute myocardial infarction correlates with the extent of endothelial dysfunction. The mechanisms described by us and other researchers may explain the role of CMV infection in atherosclerosis and development of ischemic heart disease.

Various forms of cell motility critically depend on pushing, pulling, and resistance forces generated by the actin cytoskeleton. Whereas pushing forces largely depend on actin polymerization, pulling forces responsible for cell contractility and resistance forces maintaining the cell shape require interaction of actin filaments with the multivalent molecular motor myosin II. In contrast to muscle–specific myosin II paralogs, nonmuscle myosin II (NMII) functions in virtually all mammalian cells, where it executes numerous mechanical tasks. NMII is expressed in mammalian cells as a tissue–specific combination of three paralogs, NMIIA, NMIIB, and NMIIC. Despite overall similarity, these paralogs differ in their molecular properties, which allow them to play both unique and common roles. Importantly, the three paralogs can also cooperate with each other by mixing and matching their unique capabilities. Through specialization and cooperation, NMII paralogs together execute a great variety of tasks in many different cell types. Here, we focus on mammalian NMII paralogs and review novel aspects of their kinetics, regulation, and functions in cells from the perspective of how distinct features of the three myosin II paralogs adapt them to perform specialized and joint tasks in the cells.

Cell senescence is an artificially reversible condition activated by various factors and characterized by replicative senescence and typical general alteration of cell functions, including extra–cellular secretion. The number of senescent cells increases with age and contributes strongly to the manifestations of aging. For these reasons, research is under way to obtain “senolytic” compounds, defined as drugs that eliminate senescent cells and therefore reduce aging–associated decay, as already shown in some experiments on animal models. This objective is analyzed in the context of the programmed aging paradigm, as described by the mechanisms of the subtelomere–telomere theory. In this regard, positive effects of the elimination of senescent cells and limits of this method are discussed. For comparison, positive effects and limits of telomerase activation are also analyzed, as well of the combined action of the two methods and the possible association of opportune gene modifications. Ethical issues associated with the use of these methods are outlined.

Aging diminishes individual fitness, and aging could never evolve as an adaptive program according to the most prevalent model of evolutionary theory. On the other hand, some mechanisms of aging have been found to be conserved since the Cambrian explosion, and the physiology of aging sometimes looks like programmed self–destruction. Biostatisticians find evidence of an epigenetic aging clock, extending the clock that controls the growth and development into a realm of inexorably increasing mortality. These and other observations have suggested to some biologists that our understanding of aging is being constrained by restrictive evolutionary paradigms. Several computational models have been proposed; but evolution of an aging program requires group selection on a scale that goes beyond the theory of multilevel selection, a perspective that is already controversial. So, the question whether plausible models exist that can account for aging as a group–selected adaptation is central to our understanding of what aging is, where it comes from and, importantly, how anti–aging medicine might most propitiously be pursued. In a 2016 Aging Cell article, Kowald and Kirkwood reviewed computational models that evolve aging as an adaptation. They find fault with each of these models in turn, based on theory alone, and on this basis, they endorse the standing convention that aging must be understood in terms of trade–off models. But consideration of the corpus of experimental evidence creates a picture that stands in counterpoint to the conclusions of that review. Presented herein is a broad summary of that evidence, together with a description of one model that Kowald and Kirkwood omitted, the demographic theory of aging, which may be the most conservative, and therefore most plausible of the alternative evolutionary theories, and which is the subject of a book by the present author, published contemporaneously with Kowald and Kirkwood.

Visual system is at high risk of iatrogenic damage. Laser ocular surgery, the use of powerful illumination devices in diagnostics and surgical treatment of eye diseases, as well as long surgeries under general anesthesia provoke the development of chronic degenerative changes in eye tissues, primarily in the cornea and the retina. Despite the existence of approaches for prevention and treatment of these complications, the efficacy of these approaches is often limited. Here, we review the mechanisms of iatrogenic damage to eye tissues at the cellular and biochemical levels. It is well recognized that oxidative stress is one of the main factors hindering regeneration of eye tissues after injuries and, thereby, aggravating iatrogenic eye disorders. It is accompanied by the downregulation of low–molecular–weight antioxidants and antioxidant enzymes, as well as changes in the expression and redox status of proteins in the damaged tissue. In this regard, antioxidant therapy, in particular, the use of highly effective mitochondria–targeted antioxidants such as SkQ1, is considered as a promising approach to the prevention of iatrogenesis. Recent findings indicate that the most efficient protection of eye tissues from the iatrogenic injury is achieved by preventive use of these antioxidants. In addition to preventing corneal and retinal cell death induced by oxidative stress, SkQ1 contributes to the restoration of innate antioxidant defense of these tissues and suppresses local inflammatory response. Since the timing of routine medical manipulations is usually known in advance, iatrogenic damage to the ocular tissues can be successfully prevented using mitochondria–targeted therapy.