Immunology of Aging: the Birth of Inflammaging

Abstract

The inflammaging concept was introduced in 2000 by Prof. Franceschi. This was an evolutionary or rather a revolutionary conceptualization of the immune changes in response to a lifelong stress. This conceptualization permitted to consider the lifelong proinflammatory process as an adaptation which could eventually lead to either beneficial or detrimental consequences. This dichotomy is influenced by both the genetics and the environment. Depending on which way prevails in an individual, the outcome may be healthy longevity or pathological aging burdened with aging-related diseases. The concept of inflammaging has also revealed the complex, systemic nature of aging. Thus, this conceptualization opens the way to consider age-related processes in their complexity, meaning that not only the process but also all counter-processes should be considered. It has also opened the way to add new concepts to the original one, leading to better understanding of the nature of inflammaging and of aging itself. Finally, it showed the way towards potential multimodal interventions involving a holistic approach to optimize the aging process towards a healthy longevity.

Immunosenescence and COVID-19

“…The accumulation of senescent cells in the ageing tissues is currently suggested to be one of the important causes of inflammaging ( Fulop et al, 2016 , Fulop et al, 2017a , Fulop et al, 2017b ; Fulop et al, 2020; Fulop et al, 2021 ; Pawelec et al, 2020 ; Salminen, 2021) ( Fulop et al, 2016 , Fulop et al, 2017a , Fulop et al, 2017b , Fulop et al, 2020a , Fulop et al, 2021 , Pawelec et al, 2020 , Salminen, 2021a ). However, this by no means is the sole reason for inflammaging.…”

“…Also, individuals (at any age) with paucisymptomatic chronic inflammatory diseases, sometimes not even diagnosed, would secrete more proinflammatory cytokines defining their (sometimes early) inflammaging. This process, defined as increasing the amounts of proinflammatory cytokines (as well as multiple chemokines) in the plasma of elderly without overt manifestation of inflammatory disease has broad implications for the proinflammatory and immunosuppressive state of an organism in which it develops ( Franceschi et al, 2000 , Franceschi and Campisi, 2014 , Franceschi et al, 2007 , Fulop et al, 2021 ). Clear manifestations of the latter might be the increase of numbers of the myeloid-derived suppressor cells (MDSCs) in the blood of elderly people and mice ( Flores et al, 2017 , Grizzle et al, 2007 , Verschoor et al, 2013 ).…”

CD8+ T Cell Senescence: Lights and Shadows in Viral Infections, Autoimmune Disorders and Cancer

“…The chronic inflammation observed in several autoimmune diseases may also overlap with the low-grade inflammation found in elderly people [ 62 ]. In particular, IL-6, a pro-inflammatory cytokine implicated in the cytokine storm occurring in severe COVID-19, is upregulated in both inflammaging and Rheumatoid Arthritis (RA), a chronic autoimmune rheumatic disease [ 62 , 63 , 64 , 65 , 66 ].…”

“…The chronic inflammation observed in several autoimmune diseases may also overlap with the low-grade inflammation found in elderly people [ 62 ]. In particular, IL-6, a pro-inflammatory cytokine implicated in the cytokine storm occurring in severe COVID-19, is upregulated in both inflammaging and Rheumatoid Arthritis (RA), a chronic autoimmune rheumatic disease [ 62 , 63 , 64 , 65 , 66 ]. In addition, the cartilage tissue-invasive CD4 + T cells from patients with RA showed a significant telomere frailty, a senescence hallmark, due to a low expression of the double-strand-break repair nuclease Meiotic Recombination 11 Homolog A (MRE11A) [ 67 ].…”

Guidelines for the management of acquired hemophilia A in elderly patients

“…Arthritis is also most common in people over 60. Age-related immune dysfunctions are responsible for the aging process due to impaired response to pro-inflammatory factors (inflammaging), but may also induce autoagressive diseases, including AHA [9]. Thymic involution is considered the main cause of the decreased number of naive T-cell, which favors the development of neoplastic diseases and a lower response to vaccines.…”