Targeting p53-mediated cellular senescence alleviates the progression of synucleinopathy in the brain

We found that classic senolytics, dasatinib and quercetin (D+Q) could eliminate p53-induced senescent cells in vitro and reduce senescent cells without killing senescent-like neurons in aged mice. Similar results were also observed in PFF-induced PD mice, as D+Q rescued the behavioral and pathological deficits without reducing the number of neurons in different brain regions. Collectively, our results indicated that PFF could induce both glial and neuronal senescence in multiple brain regions and senolytics D+Q could ameliorate the pathologies and behavioral deficits in PFF-induced PD mice without eliminating senescent-like neurons that may still be functioning in some way.