免疫细胞亚群与长寿的关联：心血管健康研究
Association of Immune Cell Subsets With Longevity: The Cardiovascular Health Study.
作者信息
Dobrota Lai Sylvie, Buzkova Petra, Delaney Joseph A, Olson Nels C, Psaty Bruce M, Huber Sally A, Doyle Margaret F, Tracy Russell P, Odden Michelle C
机构信息
Department of Epidemiology and Population Health, Stanford School of Medicine, Stanford, California, USA.
Department of Biostatistics, University of Washington, Seattle, Washington, USA.
出版信息
J Gerontol A Biol Sci Med Sci. 2025 Jun 10;80(7). doi: 10.1093/gerona/glaf094.
BACKGROUND
Changes in the immune system are a potential biological mechanism of aging. We investigated the association of circulating immune cell subsets with age at death and survival to age 90.
METHODS
Immune cell phenotypes were measured at baseline in 1 625 adults, aged 70-85 years, in the Cardiovascular Health Study. We selected 5 primary immune cell subsets: gamma-delta T-cells, natural killer cells, CD8+ T effector memory CD45RA expressing cells(TEMRA) cells, ratio of CD4+ to CD8+ cells, and ratio of naïve to memory CD8+ cells. We used linear regression and Poisson models, adjusting for demographics and clinical factors; and tested for effect modification by sex and race. In a secondary analysis, we investigated 23 additional immune cell subsets, using the Holm-Bonferroni method to adjust for multiple comparisons.
RESULTS
No primary immune cell subsets were significantly associated with longevity. Two secondary subsets were significantly associated with age at death. Each SD higher proportion of CD4+CD57+ cells was associated with a 0.64-year earlier death (95% CI: -0.99, -0.30) and each SD higher proportion of CD4+CD28-CD57+ cells was associated with a 0.54-year earlier death (95% CI: -0.87, -0.21). Several subsets had significant interactions with sex and race in the fully adjusted model of age at death. A higher proportion of CD4+CD57+ T-cells was significantly associated with lower likelihood of survival to age 90 (relative risk: 0.79) and 1.07-year earlier age at death in males, but not in females.
CONCLUSIONS
Our results suggest that CD4+CD57+ cells are associated with earlier death and this relationship was stronger in males than females.
背景
免疫系统的变化是衰老的一种潜在生物学机制。我们研究了循环免疫细胞亚群与死亡年龄以及活到90岁的生存率之间的关联。
方法
在心血管健康研究中，对1625名年龄在70 - 85岁的成年人进行了基线免疫细胞表型测量。我们选取了5种主要免疫细胞亚群：γδT细胞、自然杀伤细胞、表达CD45RA的CD8⁺T效应记忆细胞（TEMRA细胞）、CD4⁺与CD8⁺细胞的比例以及初始CD8⁺与记忆CD8⁺细胞的比例。我们使用线性回归和泊松模型，并对人口统计学和临床因素进行了调整；还检验了性别和种族对效应的修正作用。在一项二次分析中，我们研究了另外23种免疫细胞亚群，采用霍尔姆 - 邦费罗尼方法对多重比较进行调整。
结果
没有主要免疫细胞亚群与长寿显著相关。有两种次要亚群与死亡年龄显著相关。CD4⁺CD57⁺细胞比例每升高一个标准差，死亡时间提前0.64年（95%置信区间：-0.99，-0.30），CD4⁺CD28⁻CD57⁺细胞比例每升高一个标准差，死亡时间提前0.54年（95%置信区间：-0.87，-0.21）。在死亡年龄的完全调整模型中，有几个亚群与性别和种族存在显著的相互作用。较高比例的CD4⁺CD57⁺T细胞与男性活到90岁的可能性较低（相对风险：0.79）以及死亡年龄提前1.07年显著相关，但在女性中并非如此。
结论
我们的结果表明，CD4⁺CD57⁺细胞与较早死亡相关，且这种关系在男性中比在女性中更强。
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