Transplanting ANXA1- CD8+ Naive T cells Delay Aging Through Senolysis

Wu, Y., Guo, S., Zhang, F., Lou, F., Li, Y., Sun, Y., Shen, Q., Zhao, L., Cai, X., Wang, Z., Yang, Q., Zheng, X., Gao, M., Li, X., Deng, S., Xu, Z., Wang, H.

Precision Research Center for Refractory Diseases, Shanghai Jiao Tong University Pioneer Research Institute for Molecular and Cell Therapies, Shanghai General H · biorxiv

Paper

Abstract

Immunosenescence is a hallmark of aging, yet strategies using defined immune subsets to counteract it are largely unexplored. We performed paired scRNA/TCR-seq on CD45+ cells from human bone marrow (15 donors, 3-91 years). T cells were the most altered lineage, with CD8+ naive T cell contraction and functional impairment. We identified an expanding ANXA1+ CD8+ naive subset with senescence signatures and impaired function. ANXA1-deficient CD8+ T cells exhibited increased resting stemness and enhanced activation/cytotoxicity upon stimulation. ANXA1- cells showed senolytic activity in vitro and reduced senescence burden in vivo. Monthly transfer of syngeneic ANXA1- CD8+ naive T cells into aged mice extended median lifespan by >30 weeks, improving cardiac function, bone density, motor coordination, and marrow immune microenvironment. Our study identifies ANXA1 as critical in CD8+ naive T cell aging and establishes ANXA1- cell transfer as a strategy to counter immunosenescence and promote healthy aging.

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Research summary

The paper claims that transplanting ANXA1- CD8+ naive T cells can delay aging through senolysis. This research addresses immunosenescence, a fundamental aspect of aging, and proposes a novel strategy to counteract it, which is directly related to promoting healthy aging and lifespan extension.

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