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.
Show 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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