Perfil de quimiocinas e citocinas séricas e padrões fenotípicos de linfócitos T e B de memória ao longo do envelhecimento humano

Abstract

Population aging represents one of the most significant contemporary demographic transformations, driven by increased life expectancy and declining fertility rates, with direct implications for the organization and functionality of the immune system. In this context, this PhD thesis is derived from the integration of three complementary studies investigating immune remodeling across the life course from an immunobiographical perspective. The first study, conducted in older adults, demonstrated a rhythmic increase in circulating inflammatory mediators during aging, particularly CXCL9, CXCL10, IL-1β, IL-6, and TNF, accompanied by a reduction in global connectivity among mediators and a reorganization of inflammatory networks, with increased functional centrality of these molecules. The second study, focused on childhood and adolescence, identified a bimodal pattern in memory cell dynamics, with an initial predominance of naïve cells around 2 years of age, followed by a more pronounced expansion of memory phenotypes between 8–10 years, alongside a progressive increase in connectivity among cellular subsets, especially during adolescence. The third study, encompassing healthy individuals aged 9 months to 65 years, demonstrated that T- and B-cell memory remodeling occurs in discrete, sex-dependent waves, with the most pronounced changes observed at 5–6 years, 10–19 years, and 20–29 years; women exhibited an earlier onset of these changes, whereas men showed greater variability and expansion of differentiated subsets, including effector and interferon-mediated phenotypes. Collectively, these findings indicate that immune remodeling across the lifespan follows dynamic and interconnected patterns involving both cellular compartments and soluble mediators, reflecting cumulative processes shaped by immunobiography. These trajectories, likely modulated by antigenic exposures, environmental factors, and physiological transitions, influence the balance between trained immunity and inflammatory differentiation, ultimately contributing to interindividual variability in immune resilience and susceptibility to chronic inflammatory conditions during aging.