PATHOGENETIC SIGNIFICANCE AND BENEFITS OF MACROPHAGE TARGETING IN AGING-ASSOCIATED CHRONIC INFLAMMATION

Abstract

The review is devoted to the analysis of the pathogenetic significance of macrophages in the development of chronic inflammation associated with aging (inflammaging) and the substantiation of the prospects for targeting macrophages for the correction of age-associated diseases. The authors performed a non-systematic review of the scientific literature, including 176 sources from the international databases Lens, PubMed, Medline, Cochrane on the topic under consideration, with a search depth of 15 years (2010-2024). Macrophages play a key role in the pathogenesis of inflammation, interacting with senescent cells through the mechanisms of the secretory phenotype associated with aging (SASP). It was revealed that SASP components (IL-6, IL-10, TNF-α, TGF-β) modulate macrophage polarization via STAT3/NF-κB pathways, contributing to the formation of a functional continuum of macrophage phenotypes, including special senescence-associated phenotypes. It was established that senescent cells alter key functions of macrophages that ensure body homeostasis (phagocytosis, efferocytosis, autophagy) via expression of CD47, CD24 and activation of the JAK/STAT3 cascade, which forms a "vicious circle" of inflammaging. Promising therapeutic strategies for targeting macrophages have been identified: polarization modulation, cell therapy (autologous macrophage transplantation, CAR macrophages), effects on mitochondrial metabolism and redox signaling. Thus, participation in the regulation of inflammatory processes and high phenotypic plasticity of cells allow us to consider macrophages as a key pathogenetic target in inflammaging. Therapeutic approaches aimed at correcting impaired functions of macrophages open up new prospects for the prevention and treatment of age-associated diseases.