Data-driven transcriptomics analysis identifies PCSK9 as a novel potential liver rejuvenation agent

Aging is an inevitable process in life that leads to numerous systemic effects on the human body. Here, we investigated systematically the effect of aging on the liver using a rat model of aging using data-driven approaches. We performed systems biology approaches to analyze genome-wide transcriptomics data from liver samples obtained from 3- and 19 months old rats. We observed significant alterations in multiple biological processes, including (1) disruption of mitochondrial functions and protein synthesis, and (2) activation of immune and inflammation pathways and lipid metabolism. We validated our results in two independent aging datasets. Finally, we demonstrated the power of the co-expression network to identify novel driver genes for liver aging and confirmed our findings in human aging subjects. Overall, we identified and validated a liver-specific gene, PCSK9, as a potential therapeutic target for attenuating the aging effect on the liver. Overall design: We generated transcriptomics data from liver tissue from a total of 12 F344 rats, with 6 rats from each young (3 months) and aged (19 months) group