Nature Aging：武汉大学闫卫团队发现逆转肺纤维化和衰老的新靶点

Core Viewpoint - The study reveals that cancer cell-secreted DDAH1 protein accelerates lung aging by promoting the accumulation of citrulline, providing new insights for the treatment and diagnosis of tumors through the inhibition of aging lung fibroblasts [3][6]. Group 1: Research Findings - The research indicates that DDAH1 protein secreted by cancer cells induces the TGF-β1/Smad3 signaling pathway, leading to lung fibrosis and aging [3][6]. - The study identifies that increased levels of citrulline inhibit PAD4-mediated citrullination of TGF-β1, thereby activating the TGF-β1/Smad3 signaling pathway in lung fibroblasts [4][6]. - The use of DDAH1 inhibitors has been shown to effectively reduce lung fibrosis and delay lung aging [5][6]. Group 2: Methodology - The research utilized single-cell sequencing and gene knockout mouse experiments to confirm the mechanisms involved in the accumulation of citrulline and its effects on lung aging [4]. - The study highlights the role of vesicle sorting proteins in packaging DDAH1 into late endosomes [4]. Group 3: Implications - The findings suggest a potential therapeutic approach targeting DDAH1 to mitigate lung aging and fibrosis, which could lead to advancements in cancer treatment strategies [6].