In conclusion, the decline in autophagy during aging creates problems in cellular housekeeping functions which stimulate NF-κB signaling in order to directly or via inflammasomes trigger an age-related pro-inflammatory phenotype. Moreover, there are indications that inflammatory signaling can repress autophagy and thus induce this destructive interplay between autophagy and inflammasomes. For instance, tumor necrosis factor-α (TNF-α), an inflammatory cytokine, can induce or repress autophagy in an NF-κB-dependent manner [101]. In the presence of NF-κB signaling, TNF-α activates mTOR, a major autophagy inhibitor, whereas in cells lacking NF-κB activation, TNF-α treatment stimulates the expression of Beclin 1, an enhancer of autophagy. Both of these responses are dependent on the TNF-α-induced ROS production. Moreover, inflammaging can also enhance inflammasome activation without autophagy since e.g. glucocorticoids, known as anti-inflammatory compounds secreted with aging (see above), can strongly induce the expression of NLRP3 in macrophages [102]. Thus, it seems that the elevated cortisol level as an anti-inflammaging response could increase the priming state of inflammasomes and thus potentiate their response sensitivity during aging.
