Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging

Xu Feng, Liwen Wang, Ruoyu Zhou, Rui Zhou, Linyun Chen, Hui Peng, Yan Huang, Qi Guo, Xianghang Luo and Haiyan Zhou ()
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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
Haiyan Zhou: Xiangya Hospital of Central South University

Nature Communications, 2023, vol. 14, issue 1, 1-17

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-38842-6

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