613 Journals of Gerontology: Biological Sciences cite as: J Gerontol A Biol Sci Med Sci, 2020, Vol. 75, No. 4, 613–620 doi:10.1093/gerona/glz033 Advance Access publication February 11, 2019 © The Author(s) 2019. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. Original Article Redox Parameters as Markers of the Rate of Aging and Predictors of Life Span Irene Martínez de Toda, MSc, 1,2 Carmen Vida, PhD, 1,2 Antonio Garrido, PhD, 1,2, and Mónica De la Fuente, PhD, MD 1,2, * 1 Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, Madrid, Spain. 2 Institute of Investigation Hospital 12 Octubre, Madrid, Spain. *Address correspondence to: Mónica De la Fuente, PhD, MD, Department of Genetics, Physiology and Microbiology (Unit of Animal Physiology), Faculty of Biology, Complutense University, José Antonio Nováis 12, 28040 Madrid, Spain. E-mail: mondelaf@bio.ucm.es Received: October 25, 2018; Editorial Decision Date: January 24, 2019 Decision Editor: Rozalyn Anderson, PhD Abstract Oxidative stress has been reported to increase with aging, and although several age-related changes in redox parameters have been described, none of them have been verifed as markers of the rate of aging and life span. Therefore, antioxidant (catalase, glutathione peroxidase, reductase activities, and reduced glutathione) and oxidant (oxidized glutathione, basal superoxide anion, and malondialdehyde concentrations) parameters were studied in whole blood cells from humans divided into different age groups (adult, mature, older adult, nonagenarian, and centenarian) in a cross-sectional study. Moreover, the same parameters were investigated in peritoneal leukocytes of mice at the analogous human ages (adult, mature, old, very old, and long-lived) in a longitudinal study as well as in adult prematurely aging mice. The results reveal that the age-related alterations of these markers are similar in humans and mice, with decreased antioxidants and increased oxidants in old participants, whereas long-lived individuals show similar values to those in adults. In addition, adult prematurely aging mice showed similar values to those in chronologically old mice and had a shorter life span than nonprematurely aging mice. Thus, these parameters could be proposed as markers of the rate of aging and used to ascertain biological age in humans. Keywords: Antioxidants, Oxidants, Longevity, Biological age markers, Oxidative stress The free radical theory of aging was initially proposed by Harman (1) and then modifed and eventually merged with the “oxidative stress theory of aging,” which postulates that if free radicals cause a stress that cells can cope with, then damage will not occur because anti- oxidant defenses will overwhelm such stress. Age-associated damage will take place only when there is a shift in the pro-oxidant/antioxi- dant balance in favor of the former (2). Nowadays, this theory is highly controversial due to the appearance of studies showing that an increase in reactive oxygen species (ROS) generation, in some cases, increases longevity (3,4). Nevertheless, this outcome could be due to a hormetic response. Thus, a continued exposure to mild lev- els of ROS can activate stress response pathways that will increase expression of antioxidant enzymes, increasing metabolic health and life span, as has been previously suggested (5). Other evidence against the theory comes from epidemiological studies showing that antioxidant supplementation did not lower the incidence of many age-associated diseases but, in some cases, increased the risk of death, as reviewed in [6]. However, it has to be taken into account that a reductive stress can also lead to damage (7). Another explan- ation is that by giving powerful antioxidants, one may hamper the useful adaptations to oxidative stress (8). Nevertheless, higher oxi- dative stress markers have been reported in different tissues from old participants in several species (9,10) and humans (11,12). In addition, the participation of oxidative stress in several age-related diseases, including cardiovascular disease, atherosclerosis, arthritis, diabetes, neurodegenerative disorders, and cancer, has been observed (13,14). However, data from healthy humans along the aging pro- cess are scarce and sometimes inconsistent (15,16). Moreover, most of the research relies on cross-sectional data, given the diffculty of following-up humans during the whole aging process, and therefore, it cannot be concluded that the perceived changes are due to aging. In addition, there are not many studies that include long-lived indi- viduals. By their ability to surpass average life expectancy, naturally long-lived participants would be expected to have endured the ad- Downloaded from https://academic.oup.com/biomedgerontology/article/75/4/613/5315542 by guest on 14 June 2022