The NLRP3 Inflammasome as a Critical Actor in the Inflammaging Process

Maria Sebastian-Valverde, Giulio M Pasinetti, Maria Sebastian-Valverde, Giulio M Pasinetti

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.

Keywords: NLRP3; age-related diseases; inflammaging; innate immunity.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Age-related modifications in the cells from the innate immune system.
Figure 2
Figure 2
Mechanisms involved in inflammaging. (A) Molecular and cellular mechanisms that lead to low-grade chronic inflammation, or inflammaging. (B) Priming and activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome by danger molecules generated through mechanisms involved in inflammaging. All the mechanisms interact among them, establishing an inflammatory vicious cycle. Molecules that act as danger-associated molecular patterns (DAMPs) and trigger the transcriptional priming of the inflammasome are indicated with *, and molecules that serve as second stimuli for NLRP3 activation are highlighted in red.

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