JAK-STAT signaling
DEJAK-STAT-Signalweg
The JAK-STAT pathway is a fast signaling relay from your cell surface to its nucleus. (JAK = Janus kinase; STAT = signal transducer and activator of transcription.) Many cytokines and growth factors use it, including interferons, interleukins, and erythropoietin. Here is the relay. A signal binds its receptor, making the receptor pair up and switch on attached JAKs (JAK1, JAK2, JAK3, TYK2). Those JAKs then tag STATs (STAT1 through STAT6), which pair up, move into the nucleus, and switch on target genes. In aging, this gets dysregulated. Chronically elevated JAK-STAT signaling, driven by the SASP and inflammaging cytokines (especially the IL-6/JAK/STAT3 axis), coexists with a weaker response to actual cytokine signals. That combination feeds chronic tissue dysfunction. JAK1/2 inhibitors like ruxolitinib reduce the SASP and improve healthspan measures in aged mice, and clinical trials are underway.
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Sources
- Darnell JE Jr, Kerr IM, Stark GR. (1994). Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. *Science*doi:10.1126/science.8197455
- Shen-Orr SS, Furman D, Kidd BA, et al.. (2016). Defective signaling in the JAK-STAT pathway tracks with chronic inflammation and cardiovascular risk in aging humans. *Cell Systems*doi:10.1016/j.cels.2016.09.009