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.

doi:10.64898/2026.02.21.707223

bioRxiv · 10.64898/2026.02.21.707223

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.

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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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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.. 2026-02-23. Transplanting ANXA1- CD8+ Naive T cells Delay Aging Through Senolysis. https://doi.org/10.64898/2026.02.21.707223

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