Senescent immune cells accumulation promotes brown adipose tissue dysfunction during aging

  • Nat Commun. 2023 Jun 2;14(1):3208. doi: 10.1038/s41467-023-38842-6.
Xu Feng  1 ,  Liwen Wang  1 ,  Ruoyu Zhou  1 ,  Rui Zhou  1 ,  Linyun Chen  1 ,  Hui Peng  1 ,  Yan Huang  1 ,  Qi Guo  1 ,  Xianghang Luo  1  2  3 ,  Haiyan Zhou  4  5
Affiliations
  • 1. Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, 410008, Changsha, Hunan, China.
  • 2. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 410008, Changsha, Hunan, China.
  • 3. Key Laboratory of Organ Injury, Aging and Regenerative Medicine of Hunan Province, 410008, Changsha, Hunan, China.
  • 4. Department of Endocrinology, Endocrinology Research Center, Xiangya Hospital of Central South University, 410008, Changsha, Hunan, China. [email protected].
  • 5. National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, 410008, Changsha, Hunan, China. [email protected].
PMID: 37268694 DOI: 10.1038/s41467-023-38842-6
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.

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