Targeting Sirtuin1 to treat aging-related tissue fibrosis: From prevention to therapy

Fibrosis, which is characterized by excessive extracellular matrix (ECM) deposition, is a wound-healing response to organ injury and may promote cancer and failure in various organs, such as the heart, liver, lung, and kidney. Aging associated with oxidative stress and inflammation exacerbates cellular dysfunction, tissue failure, and body function disorders, all of which are closely related to fibrosis. Sirtuin-1 (SIRT1) is a class III histone deacetylase that regulates growth, transcription, aging, and metabolism in various organs. This protein is downregulated in organ injury and fibrosis associated with aging. Its expression and distribution change with age in different organs and play critical roles in tissue oxidative stress and inflammation. This review first described the background on fibrosis and regulatory functions of SIRT1. Second, we summarized the relationships of SIRT1 with other proteins and its protective action during fibrosis in the heart, liver, lung and kidney. Third, the activation of SIRT1 in therapies of tissue fibrosis, especially in liver fibrosis and aging-related tissue injury, was analyzed. In conclusion, SIRT1 targeting may be a new therapeutic strategy in fibrosis.