加州大学Saul A. Villeda课题组近日取得一项新成果。经过不懈努力，他们提出了衰老循环中的CD8+ T细胞及其分泌因子驱动认知能力下降。2026年5月14日出版的《免疫学》发表了这项成果。

研究人员发现衰老循环中的CD8+ T细胞及其分泌因子驱动海马依赖性认知衰退。通过异慢性异种共生和转录组学分析，小组观察到外周CD8+ T细胞保持了其年龄固有的特性。年轻小鼠全身暴露于衰老的CD8+ T细胞会引起突触相关的海马变化和认知受损，抑制激活，但不抑制浸润，减轻其促衰老作用。相反，靶向老化循环的CD8+ T细胞恢复了年轻的特征并挽救了认知。在机制上，该研究团队发现颗粒酶K （GZMK）是血浆中分泌的促衰老CD8+ T细胞衍生因子，抑制GZMK可以拯救老年动物的认知能力。总之，他们的数据确定了活化的老年CD8+ T细胞衍生的循环因子作为挽救老年认知的潜在治疗靶点。

据介绍，外周CD8+ T细胞的变化是免疫衰老的标志。然而，老化的非浸润性CD8+ T细胞在脑老化中的作用仍有待完全确定。

附：英文原文

Title: Aged circulating CD8+ T cells and their secreted factors drive cognitive decline

Author: Juliana Sucharov, Gregor Bieri, Karishma J.B. Pratt, Amber R. Philp, Turan Aghayev, Shanan Sahota, Laura Remesal, Adam B. Schroer, Cedric E. Snethlage, Rebecca Chu, Zachary J. Holmes, Julien Couthouis, Saul A. Villeda

Issue&Volume: 2026-05-14

Abstract: Changes in peripheral CD8+ T cells are a hallmark of immune aging. However, the role of aged non-infiltrating CD8+ T cells in brain aging remains to be fully defined. Here, we showed that aged circulating CD8+ T cells and their secreted factors drove hippocampal-dependent cognitive decline. Using heterochronic parabiosis and transcriptomics analysis, we observed that peripheral CD8+ T cells maintained properties intrinsic to their age. Systemic exposure of young mice to aged CD8+ T cells elicited synaptic-related hippocampal changes and impaired cognition, and inhibiting activation, but not infiltration, mitigated their pro-aging effects. Conversely, targeting aged circulating CD8+ T cells restored youthful signatures and rescued cognition. Mechanistically, we identified granzyme K (GZMK) as a secreted pro-aging CD8+ T cell-derived factor in plasma, and GZMK inhibition rescued cognition in aged animals. Together, our data identified activated aged CD8+ T cell-derived circulating factors as potential therapeutic targets to rescue cognition in old age.

DOI: 10.1016/j.immuni.2026.04.014

Source: https://www.cell.com/immunity/abstract/S1074-7613(26)00176-7

期刊信息

Immunity：《免疫》，创刊于1994年。隶属于细胞出版社，最新IF：43.474

官方网址：https://www.cell.com/immunity/home

投稿链接：https://www.editorialmanager.com/immunity/default.aspx