O impacto do meio ambiente nas assinaturas da imunossenescência

Abstract

Climate change, driven by human activities such as deforestation, pollution, and unsustainable consumption, represents a growing threat to global health by intensifying exposure to pollutants and infectious agents and promoting chronic activation of the immune system, a process associated with premature immune aging, known as immunosenescence. This phenomenon is linked to reduced immune efficiency and increased vulnerability to infections, inflammation, and chronic diseases. Although individual factors are widely recognized, the influence of collective environmental factors remains underexplored, particularly in tropical and middle-income countries. The objective of this thesis was to investigate how different environmental exposures influence the pace and profile of immunosenescence in Brazilian populations. To this end, contrasting geographic contexts in Brazil were analyzed through the integration of epigenetic analyses of biological aging, cellular immunophenotyping, cytokine quantification, and the assessment of environmental and public health indicators. In an area endemic for infectious diseases (Governador Valadares), accelerated epigenetic aging was observed, accompanied by increased production of IL-12p70, IL-17A, and IL-9. In the comparison between São Paulo (SP) and Belo Horizonte (BH), residents of SP exhibited accelerated epigenetic aging associated with increased frequencies of memory B lymphocytes and CD4+ and CD8+ T lymphocytes with exhaustion and senescence profiles, as well as higher production of Th2-associated inflammatory cytokines (IL-4, IL-5, IL-15, CCL3, G-CSF), greater exposure to air pollutants, and a higher number of hospitalizations for respiratory diseases. In contrast, in BH a more balanced immunological profile predominated, characterized by the concurrent production of inflammatory and anti-inflammatory mediators (IL-6, IL-1β, TNF-α, IL-10). As an original contribution, this thesis demonstrates in an integrated manner that contrasting environmental contexts modulate immunological and epigenetic mechanisms of human aging in a tropical country, reinforcing the need for public policies aimed at mitigating adverse environmental impacts and promoting more sustainable lifestyles.