Fig. 9.

Proposed mechanism by which DSS induces colitis and fisetin mediates restoration of colon health. DSS insult results in the accumulation of senescent cells which release SASP factors that propagate inflammation and influence neighboring cells. DSS insult also triggers inflammation which causes senescence. As a result, the biomolecular landscape is altered with changes in key mRNAs involved with senescent and inflammatory processes alongside colitis inducing miRNA signatures. Microbial dysbiosis further produces a pro-inflammatory microenvironment. Fisetin inhibits senescence and inflammation and colitis inducing miRNA signatures. Restoration of the microbiota by Fisetin treatment particularly results in increased abundance of Akkermansia mucinphila, a bacteria that is negatively correlated with senescence and inflammation. Created with BioRender.com