TGFB1 and heart failure: Since Htra3 expression was downregulated in cardiac fibroblasts in the murine and human failing heart and Htra3 overexpression in the murine heart inhibited TGF-β signaling and ameliorated cardiac dysfunction as well as fibrosis (Fig. 5h–j), Htra3-mediated prevention of cardiac fibrosis and cardiomyocyte secretory phenotype would be a novel therapeutic strategy for heart failure, in addition to senolytic therapies18,45.