IRF9 and Werner syndrome: Recent studies showed JAK-independent activation of STAT-signaling pathway in premature aging cells: The transcription factor ISGF3 (interferon stimulated gene factor 3), consisting of STAT1, STAT2, and IRF9 can induce ISG expression independently of IFN secretion in an unphosphorylated state: In aged cells and cells of patients with Werner syndrome, ISG expression was significantly upregulated compared to wild type (89, 90).