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Revealing regulatory transcription factors of aging in the kidney and kidney through multi-omics analysis

ABSTRACT: Aging is accompanied by a gradual loss of systemic metabolic homeostasis, which is maintained by multiple-organs, especially the kidney and kidney. However, a systematic study of the regulatory networks and regulatory transcription factors (TFs) of aging in the kidney and kidney remains lacking. Here, we performed an integrated analysis of multi-omics datasets in the kidney and kidney from young and aged mice, including RNA-seq, reduced representation bisulfite sequencing (RRBS) and ATAC-seq datasets, which indicated that enhanced inflammation and dysregulated metabolism were conserved signatures in aged kidney and kidney in both the transcriptome and epigenome. Transcription factor and regulatory network analysis indicated that activation of AP-1 and SPI1 was responsible for enhanced inflammation, and down-regulation of HNFs and PPARs contributed to dysregulated metabolism in aged kidney and kidney. Importantly, we found that the activation of AP-1 was cellular autonomous in aged hepatic and renal cells. However, enhanced SPI1 was caused by elevated infiltration of macrophages. Importantly, inhibition of AP-1 with small molecule combination attenuated inflammation phenotypes of aging in vivo and in vitro. Taken together, our analysis revealed common signatures and regulatory TFs of aging in the kidney and kidney, providing novel targets for the development of anti-aging interventions.

ORGANISM(S): Mus musculus

PROVIDER: GSE181797 | GEO | 2021/10/01

REPOSITORIES: GEO

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