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Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging

Author

Listed:
  • Xu Feng

    (Xiangya Hospital of Central South University)

  • Liwen Wang

    (Xiangya Hospital of Central South University)

  • Ruoyu Zhou

    (Xiangya Hospital of Central South University)

  • Rui Zhou

    (Xiangya Hospital of Central South University)

  • Linyun Chen

    (Xiangya Hospital of Central South University)

  • Hui Peng

    (Xiangya Hospital of Central South University)

  • Yan Huang

    (Xiangya Hospital of Central South University)

  • Qi Guo

    (Xiangya Hospital of Central South University)

  • Xianghang Luo

    (Xiangya Hospital of Central South University
    Xiangya Hospital
    Aging and Regenerative Medicine of Hunan Province)

  • Haiyan Zhou

    (Xiangya Hospital of Central South University
    Xiangya Hospital)

Abstract

Brown adipose tissue (BAT)-mediated thermogenesis declines with age. However, the underlying mechanism remains unclear. Here we reveal that bone marrow-derived pro-inflammatory and senescent S100A8+ immune cells, mainly T cells and neutrophils, invade the BAT of male rats and mice during aging. These S100A8+ immune cells, coupled with adipocytes and sympathetic nerves, compromise axonal networks. Mechanistically, these senescent immune cells secrete abundant S100A8 to inhibit adipose RNA-binding motif protein 3 expression. This downregulation results in the dysregulation of axon guidance-related genes, leading to impaired sympathetic innervation and thermogenic function. Xenotransplantation experiments show that human S100A8+ immune cells infiltrate mice BAT and are sufficient to induce aging-like BAT dysfunction. Notably, treatment with S100A8 inhibitor paquinimod rejuvenates BAT axon networks and thermogenic function in aged male mice. Our study suggests that targeting the bone marrow-derived senescent immune cells presents an avenue to improve BAT aging and related metabolic disorders.

Suggested Citation

  • Xu Feng & Liwen Wang & Ruoyu Zhou & Rui Zhou & Linyun Chen & Hui Peng & Yan Huang & Qi Guo & Xianghang Luo & Haiyan Zhou, 2023. "Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-38842-6
    DOI: 10.1038/s41467-023-38842-6
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