与年龄相关的免疫衰老的特征是免疫细胞亚群的变化，并且与死亡率相关。然而，由于免疫衰老与其他并发的年龄相关变化（例如炎症和多器官功能障碍）相关，因此尚不清楚年龄相关的免疫衰老与死亡率之间的关联是否独立于其他并发的年龄相关变化。为了解决这些局限性，我们在调整年龄相关炎症和生物年龄后评估了免疫细胞亚群与死亡率之间的独立关联。本研究的数据来自 2016 年健康与退休研究 (N=6802) 的采访。使用 Cox 比例风险回归模型来估计 25 个免疫细胞亚群（11 个 T 细胞亚群、4 个 B 细胞亚群、3 个单核细胞亚群、3 个自然杀伤细胞亚群、3 个树突状细胞亚群和中性粒细胞）和 4-年死亡率调整协变量，例如 Klemera-Doubal 算法生物年龄、实足年龄、性别、人种/民族、BMI、吸烟状况、合并症指数、CMV 血清阳性以及包含 C 反应蛋白和 4 种细胞因子（白细胞介素）的炎症潜变量-10、白细胞介素 1 受体拮抗剂、白细胞介素 6 和可溶性肿瘤坏死因子）。研究期间有 476 名参与者死亡，总体中位随访时间为 2.5 年。控制协变量并调整样本权重后，总 T 细胞 [HR：0.86，p=0.004]、NK CD56LO 细胞 [HR：0.88，p=0.005] 和中性粒细胞 [HR：1.22，p=0.004] 显着增加这些发现支持这样的观点，即衰老的免疫系统与短期死亡率相关，与年龄相关的炎症或其他与年龄相关的生理功能障碍指标无关。如果在其他外部队列中复制，这些发现可以确定监测和干预的新目标，以降低与年龄相关的死亡率。版权所有 © 2023 Seshadri、Vivek、Prizment、Crimmins、Klopack、Faul、Guan、Meier 和 Thyagarajan。

Age-related immunosenescence is characterized by changes in immune cell subsets and is associated with mortality. However, since immunosenescence is associated with other concurrent age-related changes such as inflammation and multi-organ dysfunction, it is unclear whether the association between age-related immunosenescence and mortality is independent of other concurrent age-related changes. To address these limitations, we evaluated the independent association between immune cell subsets and mortality after adjustment for age-related inflammation and biologic age.Data for this study was obtained from the 2016 interview of the Health and Retirement Study (N=6802). Cox proportional hazards regression models were used to estimate the association between 25 immune cell subsets (11 T-cell subsets, 4 B-cell subsets, 3 monocyte subsets, 3 natural killer cell subsets, 3 dendritic cell subsets, and neutrophils) and 4-year mortality adjusting for covariates such as the Klemera-Doubal algorithm biological age, chronological age, gender, race/ethnicity, BMI, smoking status, comorbidity index, CMV seropositivity, and inflammatory latent variable comprising C-reactive protein, and 4 cytokines (interleukin-10, interleukin-1 receptor antagonist, interleukin-6, and soluble tumor necrosis factor).Four hundred and seventy-six participants died during the study period with an overall median follow up time of 2.5 years. After controlling for covariates and adjustment for sample-weights, total T cells [HR: 0.86, p=0.004], NK CD56LO cells [HR: 0.88, p=0.005], and neutrophils [HR: 1.22, p=0.004] were significantly associated with mortality.These findings support the idea that an aging immune system is associated with short-term mortality independent of age-related inflammation or other age-related measures of physiological dysfunction. If replicated in other external cohorts, these findings could identify novel targets for both monitoring and intervention to reduce the age-related mortality.Copyright © 2023 Seshadri, Vivek, Prizment, Crimmins, Klopack, Faul, Guan, Meier and Thyagarajan.