Characteristics of the Immunoresponse in Elderly People and Autoimmunity
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acteristics of the Immunoresponse in Elderly People and Autoimmunity O. V. Moskalec* Vladimirskii Moscow Regional Research Clinical Institute, Moscow, 129110 Russia *e-mail: [email protected] Received July 19, 2019; revised January 17, 2020; accepted January 21, 2020
Abstract—Aging is a highly complex process that results in the dysregulation of all systems in the human organism. The most important changes in the immune system, which are collectively known as immunosenescence, include lower levels of immunoresponse to infections, increased levels of proinflammatory mediators, and weakened control over self-reactive clones. In elderly people, immunoscenescence is usually observed along with low-grade, aseptic inflammation (inflammaging) which is considered to be associated with a higher incidence of chronic, noninfectious, age-related diseases. This paper discusses the main changes in the innate and adaptive immunity in aging and their impact on the induction of autoimmune processes and provides data on the frequency of autoantibody detection in elderly people and the clinical patterns of certain autoimmune diseases that manifest first at this age. Keywords: immunosenescence, inflammaging, autoimmunity, autoantibodies, elderly people DOI: 10.1134/S2079057020040153
INTRODUCTION Aging is an insufficiently explored phenomenon that is associated with significant morphological and physiological changes in the organism, including the immune system. Complex rearrangement and remodeling processes take place in all of its parts. The key points are a weakened immunoresponse to pathogens and an increase in oxidative stress on a proinflammatory background, which is the result of an impaired balance between proinflammatory and anti-inflammatory factors, as well as an increase in the production of autoantibodies [16, 52]. These processes fall under various terms, including immunosenescence, immune dysregulation, and immunopause. Immune biomarkers of longevity that would make it possible to estimate the biological age and predict life expectancy are sought, and specific features of immune responsiveness in long-livers are studied [17]. It is believed that many aging cells, including immune system cells, acquire the senescence-associated secretory phenotype (SASP), which is characterized by the predominant production of proinflammatory cytokines and chemokines and is associated with the development of the chronic weak aseptic inflammation in surrounding tissues, “inflammaging” [15, 32]. Although they remain metabolically active, these cells lose the ability to divide, are less prone to apoptosis, and remain rather stable when cultured for a long period of time [19]. This phenomenon is primarily associated with different epigenetic changes that occur and accumu-
late during the life span (shortening of telomeres and a decrease in their activity, the effects of the microRNA and DNA methylation rate on gene expression, and chromatin remodeling) [32, 40, 46]. Surprisingly, centerians demonstrate a high efficiency of DNA-repair mechanism
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