Potential Role of Inflammasomes in Aging

Abstract

The aging process is associated with the emergence of low-grade, sterile inflammation, called inflammaging, which can accelerate aging-related diseases, such as neurodegenerative, cardiovascular, and musculoskeletal diseases. Recent studies have focused on the novel concept that inflammasomes represent a key innate immune pathway, mechanistically participating in aging-induced stress recognition. This review summarizes the advancements in inflammasome research related to aging. Particular attention is given to the close relationship between aging and inflammasomes and how these processes impact the health of the elderly. Inflammaging has various causes, such as metabolic disorders, changes in the gut microbiota, and immunosenescence. Hence, the connection between inflammasomes and these causes must be explored. This paper describes inflammasomes as a significant contributing factor among the mechanisms that make individuals susceptible to aging-related diseases and discusses the potential role of inflammasome regulation in effectively counteracting aging.

Keywords: NLRP3; aging; immunosenescence; inflammaging; inflammasome.

Figure 1

Inflammasome activation pathway and aging. Molecular pathways of inflammasome activation which are critically involved in inflammaging and aging. Each inflammasome sensor responds to age-associated DAMPs. Upon activation, these inflammasome complexes recruit adaptor protein ASC and activate caspase-1. This leads to cleavage of pro-inflammatory cytokines IL-1β and IL-18 into their active forms and promotes gasdermin D-mediated membrane pore formation, resulting in pyroptotic cell death. Release of these cytokines and pyroptotic debris amplifies systemic inflammation and contributes to chronic low-grade inflammation observed in aging and age-related diseases. Black solid arrows indicate mechanisms that have been clearly elucidated, whereas blue dashed arrows denote mechanisms for which conclusive evidence has not yet been established.