From Marx to Heidegger: Oscar del Barco and the crisis of Marxism

This article traces the path from Marx to Heidegger along which the Argentine philosopher Oscar del Barco responded to the crisis of Marxism. Interrogating Heidegger’s own suggestion of a ‘fruitful dialogue’ with Marx’s thinking of history and alienation, Del Barco gradually moved to a critique of Marxism as being part and parcel of the twice millenarian tradition of Western metaphysics. If, in an earlier collection such as El otro Marx, he still believed in the possibility of retrieving the ‘other side’ of capitalist reason in the margins of Marx’s texts, starting in the collection El abandono de las palabras this hope gives way to a mystical or messianic expectation to welcome the sheer ‘there is’ of being through an attitude of non-doing that would be neither nihilist nor conformist. In this sense Del Barco’s itinerary can be considered paradigmatic of the way in which a whole school of radical theory and philosophy responded to the crisis of Marxism as part of a much vaster, epochal or civilisational crisis of reason and technology in the West.

The Nitrate-Nitrite-Nitric Oxide Pathway on Healthy Ageing: A Review of Pre-clinical and Clinical Data on the Impact of Dietary Nitrate in the Elderly

We are living longer. Are we living healthier? As we age, cellular and molecular damage reshape our physiological responses towards environmental and endogenous stimuli. The free radical theory of ageing has been proposed long before ageing has been considered a “scientific discipline” and, since then, has been discussed and upgraded as a major contributor to aberrant ageing. Assuming that ageing results merely from the accumulation of oxidative modifications of biomolecules is not only a simplistic and reductive view of such a complex and dynamic process, but also free radicals and related oxidants are now considered pivotal signalling molecules. The fine modulation of critical signalling pathways by redox compounds demands a novel approach to tackle the role of free radicals in ageing. Nitric oxide (⋅NO) is a paradigmatic example given its biological functions in cardiovascular, neurologic and immune systems. In addition to the canonical ⋅NO synthesis by a family of enzymes, nitrate from green leafy vegetables, is reduced to nitrite in the oral cavity which is further reduced to ⋅NO in the stomach. Boosting this nitrate-nitrite-NO pathway has been shown to improve gastrointestinal, cardiovascular, metabolic and cognitive performance both in humans and in animal models of disease. In the elderly, nitrate-derived ⋅NO has been shown improve several physiological functions that typically decline during ageing. In this paper, the role of nitrate and derived nitrogen oxides will be discussed while reviewing pre-clinical and clinical data on the cardiovascular, neuronal, musculoskeletal and metabolic effects of nitrate during healthy ageing.

TRANSDISCIPLINARY APPROACH IN FREE RADICAL THEORY OF AGING. CONTRIBUTION OF NIKOLAY M. EMANUEL AND HIS SCIENTIFIC SCHOOL TO GERONTOLOGY

Работа представляет собой обзор научных исследований влияния антиоксидантов-геропротекторов на старение экспериментальных животных и репликативное старение диплоидных клеток человека, выполненных в отделе кинетики химических и биологических процессов «ХИМБИО» Института химической физики АН СССР под руководством академика Николая Марковича Эмануэля в 1960- 1980- е гг. В работах Н.М. Эмануэля и сотрудников было установлено неизвестное ранее явление взаимодействия ингибиторов свободнорадикальных реакций в процессах окисления органических веществ, заключающееся в регенерации более эффективного ингибитора вследствие переноса атома водорода к его радикалу от молекулы менее эффективного ингибитора. Антиоксиданты поливалентны и могут влиять одновременно на многие процессы старения. Данные научной школы Н.М. Эмануэля по увеличению средней продолжительности жизни на 25,3 % и максимальной продолжительности мышей на 55,8 % под действием антиоксидантов, полученные в результате хорошо обоснованных экспериментальных и теоретических исследований, явились весомым аргументом в пользу свободнорадикальной теории старения. The work is aimed to review the results of scientific studies of the effect of antioxidants-geroprotectors on the aging of experimental animals and the replicative aging of human diploid cells, carried out in the Department of Kinetics of Chemical and Biological Processes «KHIMBIO» of the Institute of Chemical Physics of the USSR Academy of Sciences under the leadership of academician Nikolay Markovich Emanuel in the 1960-1980s after pioneer work by D. Harman. By N.M. Emanuel and colleagues, it was established a previously unknown phenomenon of radical interaction of inhibitors in the oxidation of organic substances, which consists in the regeneration of a more effective inhibitor due to the transfer of a hydrogen atom to its free radical from a molecule of a less effective inhibitor. Antioxidants are polyvalent and can simultaneously affect many stages of aging processes. Data from the N.M. Emanuel scientific school on the increase of the average lifespan of mice by 25,3 % and their maximum lifespan by 55,8 % using antioxidants, discovered at the Institute of Chemical Physics of the USSR Academy of Sciences as a result of well-founded experimental and theoretical studies, became a powerful argument in favor of the free radical theory of aging in 1970-ties. This was further promoted by approaches based on the theory of reliability, the damage theory, and as well as an approach based on oxidative activation of the Nrf2 signaling pathway, which maintains the «nucleophilic tone» of protective oxidoreductases.

GEROPROTECTIVE PROPERTIES OF POLYPHENOLIC COMPOUNDS OF FOOD PLANTS

People’s ageing causes economic and social problems all over the world. The article presents the results of the analysis of modern research on ways and means that can eliminate the causes of ageing, prolong the active longevity and working ability of the elderly. It has been established that human health and longevity depend on the specific features of a person’s nutrition and are affected by micronutrient deficiency in the body caused by unbalanced diet. Considering the free radical theory of ageing, which is based on the chemical nature and ubiquity of free radicals, it has been found that consumption of plant foods rich in antioxidants prevents oxidative damage to cellular structures, which is caused by reactive oxygen species. It has been demonstrated that well-known plant antioxidants, such as flavonoids and other polyphenolic compounds, have a protective effect. They modulate energy metabolism in a way conducive to well-being and longevity, and reduce the risk of chronic diseases and ageing. It has been established that the antioxidant effect of flavonoids involves scavenging of free lipoperoxide radicals, inhibition of nitric oxide production, inactivation of peroxynitrite and other oxidants, inhibition of xanthine oxidase and other radical-producing enzymes, chelation of metals. Neuroprotective and radioprotective properties of flavonoids have been revealed. Flavonoids can inhibit regulatory enzymes or transcription factors that are important for the control of inflammatory mediators, affect oxidative stress through DNA interactions, and enhance genomic stability. Combinations of polyphenols can exhibit synergistic or additive beneficial effects. It has been shown that the rational use of plant-based diets rich in polyphenolic compounds helps to reduce the total mortality rate and, in particular, mortality from coronary heart disease, to maintain sustainable weight management, to decrease the frequency and severity of high-risk conditions such as obesity, hyperglycaemia, hypertension, hyperlipidemia, and improve the general condition in cases of long-neglected cardiovascular diseases and diabetes.

Evidential Decision Theory

Evidential Decision Theory is a radical theory of rational decision-making. It recommends that instead of thinking about what your decisions *cause*, you should think about what they *reveal*. This Element explains in simple terms why thinking in this way makes a big difference, and argues that doing so makes for *better* decisions. An appendix gives an intuitive explanation of the measure-theoretic foundations of Evidential Decision Theory.

Grape seed flour (GSF) extends longevity by improving multi-organ dysfunction and age-associated oxidative stress and inflammation in healthy rat

According to the free radical theory of aging, accumulation of reactive oxygen species (ROS) within mitochondria throughout lifespan leads to impairment of the main biological macromolecules as DNA, lipids and proteins, which might be at the basis of premature aging. One way to test experimentally such a hypothesis consists in intervention studies using antioxidant nutrients aimed at limiting or inhibiting ROS production that should be able to reduce the aging rate and disease pathogenesis. Grape seed flour (GSF) contains high level of phytochemicals among which bioactive polyphenols exhibit numerous biological properties and beneficial health effects as antioxidant, anti-inflammatory, anti-carcinogenic, multi-organ (heart, liver, kidney, and brain among others) protective. The present study aimed at testing the ability of high dosing GSF (4 g/kg bw) used as a nutritional supplement to slow down aging and prolong lifespan of Wistar rats when administered from early life (one month-old animals) till their natural death. Data clearly show that high dose GSF extends organism longevity and healthspan by improving multi-organ damages, systemic fuelling metabolism declines, and alleviated oxidative stress and inflammation in aging rats. Our data support the extending longevity effect of grape polyphenols especially when used as high dosing nutritional supplement or as natural medicine whose appropriate galenic form as solid lipid nanoformulation, is currently under investigation.

Antiradical activity of novel 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives

The process of studying free radicals began in the middle of the last century (the free radical theory of aging in 1956). Multiple studies have revealed the effect of free radicals on the cells of the body and the development of various diseases, such as diabetes, autoimmune diseases, diseases of the nervous system, and others. As a result, the term antioxidant has emerged, compounds that reduce and prevent the effects of free radicals. Most of the newly synthesized substances are studied for their antiradical properties. 1,2,4-Triazole derivatives are no exception, which has already proven themselves as biologically active compounds. The aim of this work was the investigation antiradical activity among 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives. Materials and methods. Previously synthesized 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives were used as test compounds. The research of antiradical activity was based on the interaction between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives and 2,2-diphenyl-1-picrylhydrazyl (DPPH) in vitro. DPPH is a stable free radical. The color of its alcoholic solutions were intense purple (λmax = 517 nm). When DPPH interacted with compounds that were capable of scavenging free radicals, it produced products. These products are yellow in color and do not absorb light of the aforementioned wavelength. The study was carried out according to the method. Results. The antiradical activity of 10 new 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives was studied. Most of the test compounds show antiradical activity against DPPH. Compound 1 was the most active at a concentration of 1 × 10-3 M and the antiradical effect was close to ascorbic acid. Conclusions. The most active compound is 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol, which in a concentration of 1 × 10-3 M has an antiradical effect in 88.89 %. When reducing the concentration to 1 × 10-4 M, also reduces the antiradical activity to 53.78 %. Some conclusions are drawn regarding the “structure – effect” dependence between 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol derivatives: – the introduction of 4-fluorobenzylidene radical (compound 2) into the 4-amino-5-(thiophen-2-ylmethyl)-4H-1,2,4-triazole-3-thiol molecule results in a slight decrease in activity; – the introduction of 2-hydroxybenzylidene radical (compound 3) into initial molecule results a high antiradical effect, which hardly changes with decreasing concentration; – transformation to 2-((5-(thiophen-2-ylmethyl)-4-((R)amino)-4H-1,2,4-triazol-3-yl)thio)acetic acid has almost no effect on antiradical activity, except for compound 9 (the antiradical effect is reduse).