The NLRP3 Inflammasome as a Critical Actor in the Inflammaging Process

Abstract

As a consequence of the considerable increase in the human lifespan over the last century, we are experiencing the appearance and impact of new age-related diseases. The causal relationships between aging and an enhanced susceptibility of suffering from a broad spectrum of diseases need to be better understood. However, one specific shared feature seems to be of capital relevance for most of these conditions: the low-grade chronic inflammatory state inherently associated with aging, i.e., inflammaging. Here, we review the molecular and cellular mechanisms that link aging and inflammaging, focusing on the role of the innate immunity and more concretely on the nucleotide-binding oligomerization domain (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, as well as how the chronic activation of this inflammasome has a detrimental effect on different age-related disorders.

Therapeutic regulation of the NLRP3 inflammasome in chronic inflammatory diseases

“…Accumulation of amyloid-β plaques in the cerebrum is the main characteristic of Alzheimer’s disease (Masters and Selkoe 2012 ). The NLRP3 inflammasome in microglia acts as an amyloid-β sensor after phagocytosis of amyloid-β accompanied by lysosomal damage and release of cathepsin B eventually culminating in IL-1β secretion (Halle et al 2008 ; Sebastian-Valverde and Pasinetti 2020 ). The levels of cleaved caspase-1 were increased in the brain of patients with Alzheimer’s disease and mild cognitive impairment (Heneka et al 2013 ).…”

Coronavirus infection: An immunologists' perspective

“…139,140 Cytokine storm appears to affect patients in severe conditions; lymphocytopenia and exhaustion or anergic responses are often reported in critical patients with COVID-19. 141 Patients who eventually enter the intensive care unit (ICU) have significantly higher plasma levels of IL-6, and IL-10, non-necessarily TNFα and fewer circulating CD4 + and CD8 + T lymphocytes, NK, and B lymphocytes. [141][142][143][144] CD8 and NK cells exhaustion markers indicate progression and prognosis of the viral infection, [142][143][144] and IL-6 appears to be the | 9 of 18 DE SANCTIS ET Al crucial cytokine in the inflammatory process.…”

“…141 Patients who eventually enter the intensive care unit (ICU) have significantly higher plasma levels of IL-6, and IL-10, non-necessarily TNFα and fewer circulating CD4 + and CD8 + T lymphocytes, NK, and B lymphocytes. [141][142][143][144] CD8 and NK cells exhaustion markers indicate progression and prognosis of the viral infection, [142][143][144] and IL-6 appears to be the | 9 of 18 DE SANCTIS ET Al crucial cytokine in the inflammatory process. 144 In animal studies, CS also impaired the development of adequate adaptive immunity against SARS-CoV infection.…”

Zapalenie starcze - mechanizmy i szlaki sygnałowe

“…inflamasomy, modulujące wydzielanie cytokin prozapalnych [20,21]. Najlepiej poznanym inflamasomem, w kontekście indukcji zapalenia starczego i chorób o podłożu zapalnym, jest inflamasom NLRP3 [33][34][35]. Aktywacja inflamasomu NLRP3 przebiega dwuetapowo.…”

“…Aktywacja DDR indukuje produkcję cytokin prozapalnych, które pobudzają sąsiadujące komórki do odpowiedzi zapalnej [9,60]. Uszkodzenia DNA na drodze pobudzania DDR mogą prowadzić do aktywacji NF-κB, a w następstwie do formowania inflamasomu NLRP3 [33].…”