AP-1 is a regulatory transcription factor of inflammaging in the murine kidney and liver

Aging is characterized by a chronic low-grade inflammation in multiple tissues, also termed as “inflammaging”, which represents a significant risk factor for many aging-related chronic diseases. However, the mechanisms and regulatory networks behind inflammaging across different tissues have not been fully elucidated. Here, by profiling transcriptomes and epigenomes of the kidney and liver from young and aged mice, we found that activation of inflammatory response was the conserved signature across tissues. Through integrative analysis, we revealed links between transcriptome change and chromatin dynamics, and identified AP-1 and ETS family transcription factors (TFs) were potential regulators of inflammaging. Further in-situ validation showed AP-1 was mainly activated in aged hepatic and renal cells, while enhanced ETS was almost caused by elevated infiltration of macrophages, indicating these TFs had different mechanisms in inflammaging. Functional data showed genetic knockdown of Fos, a major member of AP-1, significantly attenuated inflammatory response in aged kidneys and livers. Taken together, our analysis revealed conserved signatures and regulatory TFs of inflammaging in the kidney and liver, providing novel targets for the development of anti-aging interventions. Overall design: Comparative gene expression profiling analysis of RNA-seq data for kidneys and livers from aged mice treated with shNT and shFOS.