Regulation of cellular senescence by innate immunity

Abstract

During the COVID-19 pandemic, the interplay between the processes of immunity and senescence is drawing more and more intensive attention. SARS-CoV-2 infection induces senescence in lung cells, failure to clear infected cells and increased presence of inflammatory factors could lead to a cytokine storm and acute respiratory disease syndrome (ARDS), which together with aging and age-associated disease lead to 70% of COVID-19-related deaths. Studies on how senescence initiates upon viral infection and how to restrict excessive accumulation of senescent cells to avoid harmful inflammation are crucially important. Senescence can induce innate immune signaling, and innate immunity can engage cell senescence. Here, we mainly review the innate immune pathways, such as cGAS-STING, TLRs, NF-κB, and NLRP3 inflammasome, participating in the senescence process. In these pathways, IFN-I and inflammatory factors play key roles. At the end of the review, we propose the strategies by which we can improve the immune function and reduce inflammation based on these findings.

Graphical abstract

Keywords

IFN-I / NF-κB / cGAS-STING / TLRs / NLRP3 inflammasome / Cell senescence

Acknowledgements

This work was supported in part by grants from the Natural Science Foundation of China (82201935), the Natural Science Foundation of Shandong Province (ZR2022QH020), and the China Postdoctoral Science Foundation (2022M711901).

RIGHTS & PERMISSIONS

2023 The Author(s)