A Tale of Two Concepts: Harmonizing the Free Radical and Antagonistic Pleiotropy Theories of Aging

Golubev, A. G.; Hanson, Andrew D.; Gladyshev, Vadim N.

doi:10.1089/ars.2017.7105

Cited by 29 publications

(8 citation statements)

References 142 publications

(154 reference statements)

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“…The effects of the respective genes are both beneficial, as far as they are mediated by superoxide, and detrimental, as far as hydroxyl radicals are generated from superoxide via Haber-Weiss reaction. This provides reasons to regard the effects of these genes as antagonistically pleiotropic and thus points out another aspect of the relevance of the definition of aging suggested herein to the evolutionary theories of aging (Golubev et al 2017b;Golubev 2019b).…”

Section: The Real Definition Of Aging By Genesis Vs Manifestations Of Aging Used In Its Nominal Definitionsmentioning

confidence: 73%

“…It has been suggested earlier (Golubev 1996 , 2009 ; Golubev et al 2017a , b ) that the driving force of aging is, in other words aging is generated by, the chemical reactivity of the rapidly turning-over small metabolites applied to the slowly turning-over macromolecules implicated in metabolic control. Based on this proposal and by analogy with the above physical definition of work, aging may be defined as the product of the chemical interactions between the free metabolites and the metabolites incorporated in macromolecules.…”

Section: Physics As a Paragonmentioning

confidence: 99%

“…Interestingly, most of such non-enzymatic processes involve chemical reactions honored with proper names, such as Haber–Weiss reaction, Michael addition, Pictet–Spengler reaction, Schiff base formation, Amadori rearrangement, Mannich reaction, etc. (Golubev 1996 ; Golubev et al 2017a , b ), just because they are typical and realizable under even mild conditions when the respective reactant molecules collide.…”

Section: The Evolutionary Justification For Introducing Chemistry Into the Real Definition Of Agingmentioning

confidence: 99%

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An essay on the nominal vs. real definitions of aging

Golubev

2021

Biogerontology

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In the current literature, the definitions of aging range from relying on certain sets of distinctive features at the molecular, organismal, populational and/or even evolutional levels/scales to declaring it a treatable disease and, moreover, to treating aging as a mental construct rather than a natural phenomenon. One reason of such a mess may be that it is common in the natural sciences to disregard philosophy of science where several categories of definitions are recognized, among which the nominal are less, and the so-called real ones are more appropriate in scientific contexts. E.g., water is, by its nominal definition, a liquid having certain observable features and, by its real definition, a specific combination (or a product of interaction) of hydrogen and oxygen atoms. Noteworthy, the real definition is senseless for people ignorant of atoms. Likewise, the nominal definition of aging as a set of observable features should be supplemented, if not replaced, with its real definition. The latter is suggested here to imply that aging is the product of chemical interactions between the rapidly turning-over free metabolites and the slowly turning-over metabolites incorporated in macromolecules involved in metabolic control. The phenomenon defined in this way emerged concomitantly with metabolic pathways controlled by enzymes coded for by information-storing macromolecules and is inevitable wherever such conditions coincide. Aging research, thus, is concerned with the elucidation of the pathways and mechanisms that link aging defined as above to its hallmarks and manifestations, including those comprised by its nominal definitions. Esoteric as it may seem, defining aging is important for deciding whether aging is what should be declared as the target of interventions aimed at increasing human life and health spans.

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Section: The Real Definition Of Aging By Genesis Vs Manifestations Of Aging Used In Its Nominal Definitionsmentioning

confidence: 73%

Section: Physics As a Paragonmentioning

confidence: 99%

Section: The Evolutionary Justification For Introducing Chemistry Into the Real Definition Of Agingmentioning

confidence: 99%

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An essay on the nominal vs. real definitions of aging

Golubev

2021

Biogerontology

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“…These time-related variations are attributed to the aging procedure. The nature of the aging procedure has been the subject of considered theory (Golubev et al, 2018). According to (Omayma et al, 2020), oxidative chemicals result in alteration in nucleic acid repair system leading to excessive production of reactive oxygen species.…”

Section: Discussionmentioning

confidence: 99%

Neuromodulatory Influences of vitamin C on D-galactose Induced Neuronal Metabolic Dysfunction Model

Mohammed

Moawed

zaid

et al. 2021

Benha Veterinary Medical Journal

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Aging is a physiological, non-pathological process that occurs mostly as passive, gradual and slow procedure affected by interplay of frequent environmental and genetic influences. Different ways have been tried to postponement aging and extent life span in animals; dietary antioxidants are one of them. Depending on the metabolic and free radical theories of aging, this work was carried out to evaluate the use of vitamin C in male rats, we used tree groups, control which received no treatment, experimental group which received the aging promoter agent and then subdivided into two groups one of which received Vitamin C while the other left. This study was carried out shedding the light on aging mechanisms underlying the antiaging variations on both the molecular and the physiological level. Aging was enhanced by injecting rats subcutaneously with D galactose in a dose of 100 mg for 8 weeks brain tissues were subjected to analysis determining the level of serotonin, dopamine and nor epinephrine. D galactose caused down regulation of both serotonin, dopamine and BCL2, while nor epinephrine and BAX went up, histopathological, d-galactose caused severe damage in brain tissues such alteration has been resisted in rats administrated vitamin C. Thus, we can conclude that antioxidants could prevent the age-related brain deterioration.

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“…The relevance of the excessive chemical potencies of glucose and other metabolites to the theories of the evolutionary origin and development of aging is discussed elsewhere ( Golubev, 2009 ; Golubev et al, 2017a , b ; Golubev, 2019 ). As to COVID-19 pathophysiology, reduced glucose tolerance is a hallmark of poor metabolic fitness manifested in obesity and hyperlipidemia.…”

Section: Pathophysiological Implicationsmentioning

confidence: 99%

COVID-19: A Challenge to Physiology of Aging

Golubev

2020

Front. Physiol.

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The death toll of the current COVID-19 pandemic is strongly biased toward the elderly. COVID-19 case fatality rate (CFR) increases with age exponentially, its doubling time being about 7 years, irrespective of countries and epidemic stages. The same age-dependent mortality pattern known as the Gompertz law is featured by the total mortality and its main constituents attributed to cardiovascular, metabolic, neurological, and oncological diseases. Among patients dying of COVID-19, most have at least one of these conditions, whereas none is found in most of those who pass it successfully. Thus, gerontology is indispensable in dealing with the pandemic, which becomes a benchmark for validating the gerontological concepts and advances. The two basic alternative gerontological concepts imply that either aging results from the accumulation of stochastic damage, or is programmed. Based on these different grounds, several putative anti-aging drugs have been proposed as adjuvant means for COVID-19 prevention and/or treatment. These proposals are reviewed in the context of attributing the molecular targets of these drugs to the signaling pathways between the sensors of resource availability and the molecular mechanisms that allocate resources to storage, growth and reproduction or to self-maintenance and repair. Each of the drugs appears to reproduce only a part of the physiological responses to reduced resource availability caused by either dietary calories restriction or physical activity promotion, which are the most robust means of mitigating the adverse manifestations of aging. In the pathophysiological terms, the conditions of the endothelium, which worsen as age increases and may be significantly improved by the physical activity, is a common limiting factor for the abilities to withstand both physical stresses and challenges imposed by COVID-19. However, the current anti-epidemic measures promote sedentary indoor lifestyles, at odds with the most efficient behavioral interventions known to decrease the vulnerability to both the severe forms of COVID-19 and the prevalent aging-associated diseases. To achieve a proper balance in public health approaches to COVID-19, gerontologists should be involved in crosstalk between virologists, therapists, epidemiologists, and policy makers. The present publication suggests a conceptual background for that.

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A Tale of Two Concepts: Harmonizing the Free Radical and Antagonistic Pleiotropy Theories of Aging

Abstract: The manifestations of ROS-mediated cumulative chemical damage at the population level may include the often-observed negative correlation between fitness and the rate of its decline with increasing age, further linking FRT and APT. Antioxid. Redox Signal. 29, 1003-1017.

Cited by 29 publications

References 142 publications

An essay on the nominal vs. real definitions of aging

An essay on the nominal vs. real definitions of aging

Neuromodulatory Influences of vitamin C on D-galactose Induced Neuronal Metabolic Dysfunction Model

COVID-19: A Challenge to Physiology of Aging

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