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Liver aging

Aging breaks liver vascular ‘zone defense’

Nature Aging volume 3, pages 242–243 (2023)Cite this article

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Wang Lin and his colleagues explore how aging reprograms spatially unique pathways in liver endothelial cells to cause fibrosis. They find that loss of KIT in liver endothelial cells close to the central vein upregulates the chemokine receptor CXCR4 to stimulate inflammation, enhance fibrosis and increase lipid accumulation in aged liver.

The liver vascular system has a unique architecture, with the portal vein collecting blood from the gastrointestinal system and the hepatic artery delivering blood from systemic circulation. Both circulations distribute blood into the liver sinusoids to exchange components with adjacent hepatocytes, which drain to a central vein in the liver. In addition to its metabolic function, the liver also has a remarkable capacity to regenerate lost mass and function. In this regeneration process, liver sinusoid endothelial cells (LSECs) supply paracrine (angiocrine) factors to orchestrate hepatocyte propagation6,7,8. Nevertheless, in aging or in metabolic disorders such as NASH, LSECs have a divergent role in releasing profibrotic factors to promote the regeneration-to-fibrotic transition, resulting in liver fibrosis9,10,11,12. Depending on their distance from the portal and central veins, LSECs can be categorized into different zones (such as pericentral LSECs or periportal LSECs) and exhibit zone-specific molecular signatures. Therefore, defining the phenotypes and functions of spatially heterogenous liver endothelial cells is important in understanding how the vascular niche balances organ regeneration and fibrosis.

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Fig. 1: Aging suppresses the spatially specific marker KIT in LSECs to induce CXCR4.

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Acknowledgements

We are grateful to Y. Ren and X. Huang for their helpful discussion and input. The authors are supported by National Natural Science Foundation of China (82125002, 81925005, 92268201, U21A20333).

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Authors and Affiliations

  1. Key Laboratory of Birth Defects and Related Diseases of Women and Children of MOE, State Key Laboratory of Biotherapy, NHC Key Laboratory of Chronobiology, Development and Related Diseases of Women and Children, Key Laboratory of Sichuan Province, West China Second University Hospital, Sichuan University, Chengdu, China

    Zhongwei Cao & Bi-Sen Ding

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  1. Zhongwei Cao
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  2. Bi-Sen Ding
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Correspondence to Zhongwei Cao or Bi-Sen Ding.

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Cao, Z., Ding, BS. Aging breaks liver vascular ‘zone defense’. Nat Aging 3, 242–243 (2023). https://doi.org/10.1038/s43587-023-00371-8

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