Inflammaging in Endemic Areas for Infectious Diseases

Abstract

Immunosenescence is marked by a systemic process named inflammaging along with a series of defects in the immunological activity that results in poor responses to infectious agents and to vaccination. Inflammaging, a state of low-grade chronic inflammation, usually leads to chronic inflammatory diseases and frailty in the elderly. However, some elderly escape from frailty and reach advanced age free of the consequences of inflammaging. This process has been called immunological remodeling, and it is the hallmark of healthy aging as described in the studies of centenarians in Italy. The biological markers of healthy aging are still a matter of debate, and the studies on the topic have focused on inflammatory versus remodeling processes and molecules. The sub-clinical inflammatory status associated with aging might be a deleterious event for populations living in countries where chronic infectious diseases are not prevalent. Nevertheless, in other parts of the world where they are, two possibilities may occur. Inflammatory responses may have a protective effect against these infectious agents. At the same time, the long-term consequences of protective immune responses during chronic infections may result in accelerated immunosenescence in these individuals. Therefore, the biological markers of healthy aging can vary according to environmental, cultural, and geographical settings that reflect worldwide, and in a non-biased, non-westernized perspective, the changes that we experience regarding our contacts with microorganisms and the outcomes of such contacts.

The Frailty Puzzle: Searching for Immortality or for Knowledge Survival?

“…It is a partial view since the list of the age-associated clinical and biological parameters which have been used for frailty indices is, to date, almost endless ( Rivero-Segura et al, 2020 ; for a categorization and an analysis see Lohman et al, 2021 ). Among those not here considered, just to mention some markers that have been thoroughly investigated, are the age-associated changes in the immunological ( Fahy et al, 2019 ; Sayed et al, 2021 ) and in the inflammatory responses which are somewhat linked ( Batista et al, 2020 ), in oxidative stress/antioxidant reserves ( Kameda et al, 2020 ) or telomer length ( Vaiserman and Krasnienkov, 2021 ). Likely the future development of frailty and longevity indices, able to predict residual life expectancy and health, will rely on the composite use of several clinical and biological markers optimized using machine learning programs.…”

Physical Activity and Nutritional Influence on Immune Function: An Important Strategy to Improve Immunity and Health Status

“…Indeed, an imbalanced cytokine expression represents a hallmark of the aging process, as confirmed by an overall increase in c-reactive protein (CRP), impairment of transforming growth factor-beta (TGF β) pathway and other cytokines, such as IL-4 and IL-10 (Ferrucci and Fabbri, 2018;Kong et al, 2020). This contributes to a significant age-related reduction in inflammation, leading to a higher risk of mortality in the elderly population (Batista et al, 2020). Aging caused a decrease the production of IL-12, a fundamental interleukin required for T-cell immune response, decreases, resulting in an impairment of the antigen presentation process mediated by accessory cells such as dendritic and langerhans cells (Mbongue et al, 2014).…”

Oral tolerance as antigen-specific immunotherapy

“…Others have reported reduced production of secretory IgA in aged mice [ 164 ]. On the other hand, humans preserve their ability to produce CD4+CD25 +Foxp3+ iTreg during inflammatory and infectious diseases [ 165 ]. Interestingly, aged mice that are refractory to oral tolerance induction by gavage can be effectively rendered tolerant by continuous feeding of antigen confirming the robustness of this protocol of feeding [ 147 , 148 ].…”