전지혜 (Duke University)

한빛사논문

조회542

전지혜Ji Hye Jun

Duke University

CV File 188 kb

Nature Aging, Volume 4 Issue 7, July 2024 | https://doi.org/10.1038/s43587-024-00652-w Aging promotes metabolic dysfunction-associated steatotic liver disease by inducing ferroptotic stress

Kuo Du^1,3, Liuyang Wang^2,3, Ji Hye Jun^1,3, Rajesh K. Dutta¹, Raquel Maeso-Díaz¹, Seh Hoon Oh¹, Dennis C. Ko² & Anna Mae Diehl¹

¹Department of Medicine, Duke University, Durham, NC, USA.

²Department of Molecular Genetics and Microbiology, Duke University, Durham, NC, USA.

³These authors contributed equally: Kuo Du, Liuyang Wang, Ji Hye Jun.

Corresponding author

Correspondence to Anna Mae Diehl.

Abstract

Susceptibility to the biological consequences of aging varies among organs and individuals. We analyzed hepatocyte transcriptomes of healthy young and aged male mice to generate an aging hepatocyte gene signature, used it to deconvolute transcriptomic data from humans and mice with metabolic dysfunction-associated liver disease, validated findings with functional studies in mice and applied the signature to transcriptomic data from other organs to determine whether aging-sensitive degenerative mechanisms are conserved. We discovered that the signature enriches in diseased livers in parallel with degeneration. It is also enriched in failing human hearts, diseased kidneys and pancreatic islets from individuals with diabetes. The signature includes genes that control ferroptosis. Aged mice develop more hepatocyte ferroptosis and liver degeneration than young mice when fed diets that induce metabolic stress. Inhibiting ferroptosis shifts the liver transcriptome of old mice toward that of young mice and reverses aging-exacerbated liver damage, identifying ferroptosis as a tractable, conserved mechanism for aging-related tissue degeneration.

논문정보

형식Research article
게재일2024년 07월 (BRIC 등록일 2024-07-23)
연구진국외 연구진
분야 생명과학 > 세포생물학

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