Upregulated FASN-mediated lipogenesis in senescent macrophages contributes to liver fibrosis progression

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Middle-aged mice exhibited more severe liver fibrosis and senescence compared to young mice after CCl4 treatment.
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Senescent macrophages showed increased expression of SASP components and promoted activation of hepatic stellate cells.
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Transcriptome sequencing revealed metabolic reprogramming in senescent macrophages, with upregulation of fatty acid synthesis genes.
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FASN protein in senescent macrophages underwent dual degradation via ubiquitin-proteasome and autophagy pathways.
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Pharmacological inhibition of FASN reduced the DNA damage response in senescent macrophages.

Frontiers In Immunology

by Hongliang Dong, Chuanfang Shu, Ran Liu, Mingpei Zhao, Kaiyue Zhang, Ziqun Qu, Lili Wang, Jing Fan, Wei Ye
July 14, 2026

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