主观压力与临床正常成年人中单核细胞/巨噬细胞衰老轨迹加速相关。
Perceived Stress is Associated with Accelerated Monocyte/Macrophage Aging Trajectories in Clinically Normal Adults.
机构信息
Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA.
Memory and Aging Center, Department of Neurology, University of California, San Francisco, CA.
出版信息
Am J Geriatr Psychiatry. 2018 Sep;26(9):952-963. doi: 10.1016/j.jagp.2018.05.004. Epub 2018 Jun 18.
OBJECTIVES
Chronic stress is associated with poorer age-related cognition, but the mechanisms of this relationship are not well understood. Aging increases expression of activated macrophages, leading to exacerbated immune responses to stressors. We examined the impact of stress and aging on macrophage-related inflammation and cognition in clinically normal adults.
METHODS
Three hundred eighty clinically normal adults were followed longitudinally (age M = 73 years; visit range: 1-8; M = 2.5 visits). Participants completed the Perceived Stress Scale, a neuropsychological battery, and blood draws. Plasma was analyzed for cytokines related to macrophage function (interleukin 6, tumor necrosis factor alpha, macrophage inflammatory protein-1 alpha, macrophage inflammatory protein-1 beta). Linear mixed-effects examined the effects of age, baseline stress, and their interaction predicting macrophage cytokines, adjusting for sex, education, and depressive symptoms. Latent growth curve models assessed the mediating role of macrophage cytokines in the relationship between age and cognition in high or low stress.
RESULTS
Baseline perceived stress interacted with age to predict macrophage cytokines longitudinally. Specifically, high-stress adults demonstrated accelerated age-related elevations in macrophage cytokines across time. Macrophage cytokines negatively tracked with executive functioning longitudinally. Macrophage cytokines mediated 19% of the relationship between age and executive function in high-stress, but not low-stress, adults.
CONCLUSIONS
Our data provide evidence of accelerated immune aging among individuals with high stress. Elevated macrophage cytokine trajectories mediated the effect of age on executive function only in individuals with high stress, suggesting these constructs may be more tightly linked in elevated stress contexts. Stress interventions are warranted to optimize immune aging, with possible downstream cognitive benefits among even clinically normal adults.
目的
慢性压力与较差的与年龄相关的认知有关，但这种关系的机制尚不清楚。衰老会增加激活的巨噬细胞的表达，导致对压力源的免疫反应加剧。我们研究了压力和衰老对临床正常成年人中与巨噬细胞相关的炎症和认知的影响。
方法
380 名临床正常成年人进行了纵向随访（年龄 M=73 岁；随访范围：1-8；M=2.5 次随访）。参与者完成了感知压力量表、神经心理学测试和血液采集。对与巨噬细胞功能相关的细胞因子（白细胞介素 6、肿瘤坏死因子 alpha、巨噬细胞炎性蛋白-1 alpha、巨噬细胞炎性蛋白-1 beta）进行了血浆分析。线性混合效应检验了年龄、基线压力及其交互作用对巨噬细胞细胞因子的影响，同时调整了性别、教育程度和抑郁症状。潜在增长曲线模型评估了巨噬细胞细胞因子在高或低压力下年龄与认知之间关系中的中介作用。
结果
基线感知压力与年龄相互作用，预测巨噬细胞细胞因子的纵向变化。具体来说，高压力组的巨噬细胞细胞因子在整个时间内呈现加速的与年龄相关的升高。巨噬细胞细胞因子与执行功能呈负相关。在高压力而非低压力的成年人中，巨噬细胞细胞因子解释了年龄与执行功能之间 19%的关系。
结论
我们的数据提供了证据，表明高压力个体的免疫衰老加速。在高压力个体中，升高的巨噬细胞细胞因子轨迹仅介导了年龄对执行功能的影响，这表明这些结构在压力升高的情况下可能更为紧密地联系在一起。需要进行压力干预以优化免疫衰老，即使在临床正常成年人中也可能带来认知上的好处。
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