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      An essay on the nominal vs. real definitions of aging

      research-article
      Biogerontology
      Springer Netherlands
      Aging, Metabolism, Evolution, Philosophy of science

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          Abstract

          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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          Most cited references91

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          The Hallmarks of Aging

          Aging is characterized by a progressive loss of physiological integrity, leading to impaired function and increased vulnerability to death. This deterioration is the primary risk factor for major human pathologies, including cancer, diabetes, cardiovascular disorders, and neurodegenerative diseases. Aging research has experienced an unprecedented advance over recent years, particularly with the discovery that the rate of aging is controlled, at least to some extent, by genetic pathways and biochemical processes conserved in evolution. This Review enumerates nine tentative hallmarks that represent common denominators of aging in different organisms, with special emphasis on mammalian aging. These hallmarks are: genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, deregulated nutrient sensing, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. A major challenge is to dissect the interconnectedness between the candidate hallmarks and their relative contributions to aging, with the final goal of identifying pharmaceutical targets to improve human health during aging, with minimal side effects. Copyright © 2013 Elsevier Inc. All rights reserved.
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            Reactive oxygen species (ROS) as pleiotropic physiological signalling agents

            'Reactive oxygen species' (ROS) is an umbrella term for an array of derivatives of molecular oxygen that occur as a normal attribute of aerobic life. Elevated formation of the different ROS leads to molecular damage, denoted as 'oxidative distress'. Here we focus on ROS at physiological levels and their central role in redox signalling via different post-translational modifications, denoted as 'oxidative eustress'. Two species, hydrogen peroxide (H2O2) and the superoxide anion radical (O2·-), are key redox signalling agents generated under the control of growth factors and cytokines by more than 40 enzymes, prominently including NADPH oxidases and the mitochondrial electron transport chain. At the low physiological levels in the nanomolar range, H2O2 is the major agent signalling through specific protein targets, which engage in metabolic regulation and stress responses to support cellular adaptation to a changing environment and stress. In addition, several other reactive species are involved in redox signalling, for instance nitric oxide, hydrogen sulfide and oxidized lipids. Recent methodological advances permit the assessment of molecular interactions of specific ROS molecules with specific targets in redox signalling pathways. Accordingly, major advances have occurred in understanding the role of these oxidants in physiology and disease, including the nervous, cardiovascular and immune systems, skeletal muscle and metabolic regulation as well as ageing and cancer. In the past, unspecific elimination of ROS by use of low molecular mass antioxidant compounds was not successful in counteracting disease initiation and progression in clinical trials. However, controlling specific ROS-mediated signalling pathways by selective targeting offers a perspective for a future of more refined redox medicine. This includes enzymatic defence systems such as those controlled by the stress-response transcription factors NRF2 and nuclear factor-κB, the role of trace elements such as selenium, the use of redox drugs and the modulation of environmental factors collectively known as the exposome (for example, nutrition, lifestyle and irradiation).
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              Geroscience: linking aging to chronic disease.

              Mammalian aging can be delayed with genetic, dietary, and pharmacologic approaches. Given that the elderly population is dramatically increasing and that aging is the greatest risk factor for a majority of chronic diseases driving both morbidity and mortality, it is critical to expand geroscience research directed at extending human healthspan.
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                Author and article information

                Contributors
                lxglbv@rambler.ru
                Journal
                Biogerontology
                Biogerontology
                Biogerontology
                Springer Netherlands (Dordrecht )
                1389-5729
                1573-6768
                6 June 2021
                : 1-17
                Affiliations
                Department of Carcinogenesis and Oncogerontology, N.N. Petrov National Medical Research Center of Oncology, Saint Petersburg, Russia
                Author information
                http://orcid.org/0000-0002-2129-6205
                Article
                9926
                10.1007/s10522-021-09926-x
                8180187
                34091822
                1c4c41e6-e072-429d-a64b-2cbcdeb31d31
                © The Author(s), under exclusive licence to Springer Nature B.V. 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 8 April 2021
                : 31 May 2021
                Categories
                Opinion

                Geriatric medicine
                aging,metabolism,evolution,philosophy of science
                Geriatric medicine
                aging, metabolism, evolution, philosophy of science

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