Our previous study showed that the essential caveolar component PTRF was up‐regulated and promoted caveolae formation in senescent cells. Additionally, we found that overexpression of PTRF increased the number of caveolae and induced cellular senescence. Unresponsiveness to growth factor is one of the fundamental characteristics of senescent cells, although normal levels of receptors and downstream signaling molecules are present in senescent cells. We investigated the role of PTRF in the regulation of growth factor PDGF signaling in young and senescent cells. We first confirmed that PTRF was up‐regulated in senescent human fibroblasts and aged mouse tissues. We then examined the activation of ERK kinases in young and senescent cells after PDGF stimulation. Our results showed that expression of PDGFRs was not altered during cellular senescence. Interestingly, phosphorylation of ERK1/2 was induced upon PDGF stimulation in young, replicating cells but not in senescent cells. Induction of ERK1/2 phosphorylation was impaired in senescent cells and PTRF‐over‐expressed, pre‐senescent cells. Furthermore, our results showed that PTRF interacted with PDGFRs, and this interaction was increased in senescent cells. These results suggest that the unresponsiveness of senescent fibroblasts to PDGF stimulation may be due to increased levels of PTRF and the formation of caveolae, which in turn sequester growth receptors such as the PDGFR and its signaling molecules. This article is protected by copyright. All rights reserved.