PTCHD4 Promotes Cellular Senescence and Age-Related Pathologies via AKT Signaling

This study investigates the role of the transmembrane protein PTCHD4 in cellular and organismal age-related processes. We demonstrate that PTCHD4 expression is significantly upregulated in various senescence models, including replicative and stress-induced senescence in human and mouse cells, and in multiple tissues of physiologically aged mice.

Functionally, PTCHD4 deficiency attenuated the progression of cellular senescence, whereas its overexpression was shown to accelerate it. At the organismal level, PTCHD4 deficiency extended median lifespan and improved age-related declines in motor function, cognitive performance and metabolic homeostasis. In a bleomycin-induced pulmonary fibrosis model, PTCHD4 deficiency reduced lung fibrosis and preserved pulmonary function.