Acid ceramidase promotes senescent cell survival
Rachel Munk, Carlos Anerillas, Martina Rossi, Dimitrios Tsitsipatis, Jennifer L. Martindale, Allison B. Herman, Jen‐Hao Yang, Jackson A. Roberts, Vijay R. Varma, Poonam R. Pandey, Madhav Thambisetty, Myriam Gorospe, Kotb Abdelmohsen
Abstract
mRNA and a robust increase in ASAH1 protein stability. Furthermore, silencing ASAH1 in pre-senescent fibroblasts decreased the levels of senescence proteins p16, p21, and p53, and reduced the activity of the senescence-associated β-galactosidase. Interestingly, depletion of ASAH1 in pre-senescent cells sensitized these cells to the senolytics Dasatinib and Quercetin (D+Q). Together, our study indicates that ASAH1 promotes senescence, protects senescent cells, and confers resistance against senolytic drugs. Given that inhibiting ASAH1 sensitizes cells towards senolysis, this enzyme represents an attractive therapeutic target in interventions aimed at eliminating senescent cells.