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Role of macrophages in age-related oxidative stress and lipofuscin accumulation in mice

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Vida, Carmen and Martínez de Toda Cabeza, Irene and Cruces, Julia and Garrido Tarrio, Antonio and González Sánchez, Mónica and Fuente del Rey, Mónica de la (2017) Role of macrophages in age-related oxidative stress and lipofuscin accumulation in mice. Redox Biology, 12 . pp. 423-437. ISSN 2213-2317

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Official URL: https://www.journals.elsevier.com/redox-biology/



Abstract

The age-related changes in the immune functions (immunosenescence) may be mediated by an increase of oxidative stress and damage affecting leukocytes. Although the “oxidation-inflammation” theory of aging proposes that phagocytes are the main immune cells contributing to “oxi-inflamm-aging”, this idea has not been corroborated. The aim of this work was to characterize the age-related changes in several parameters of oxidative stress and immune function, as well as in lipofuscin accumulation (“a hallmark of aging”), in both total peritoneal leukocyte population and isolated peritoneal macrophages. Adult, mature, old and long-lived mice (7, 13, 18 and 30 months of age, respectively) were used. The xanthine oxidase (XO) activity-expression, basal levels of superoxide anion and ROS, catalase activity, oxidized (GSSG) and reduced (GSH) glutathione content and lipofuscin levels, as well as both phagocytosis and digestion capacity were evaluated. The results showed an age-related increase of oxidative stress and lipofuscin accumulation in murine peritoneal leukocytes, but especially in macrophages. Macrophages from old mice showed lower antioxidant defenses (catalase activity and GSH levels), higher oxidizing compounds (XO activity/expression and superoxide, ROS and GSSG levels) and lipofuscin levels, together with an impaired macrophage functions, in comparison to adults. In contrast, long-lived mice showed in their peritoneal leukocytes, and especially in macrophages, a well-preserved redox state and maintenance of their immune functions, all which could account for their high longevity. Interestingly, macrophages showed higher XO activity and lipofuscin accumulation than lymphocytes in all the ages analyzed. Our results support that macrophages play a central role in the chronic oxidative stress associated with aging, and the fact that phagocytes are key cells contributing to immunosenescence and “oxi-inflamm-aging”. Moreover, the determination of oxidative stress and immune function parameters, together with the lipofuscin quantification, in macrophages, can be used as useful markers of the rate of aging and longevity.


Item Type:Article
Uncontrolled Keywords:Aging; Immune functions; Lipofuscin; Longevity; Macrophages; Oxidative stress
Subjects:Medical sciences > Biology > Animal physiology
Medical sciences > Biology > Genetics
ID Code:43966
Deposited On:19 Jul 2017 07:13
Last Modified:10 Dec 2018 15:30

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