Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA; Department of Psychiatry and Neurosciences, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany; Berlin Institute of Health (BIH), Berlin, Germany.
Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, Department of Psychiatry and Biobehavioral Sciences, David Geffen School of Medicine, University of California Los Angeles (UCLA), Los Angeles, CA, USA.
Brain Behav Immun. 2022 Nov;106:67-75. doi: 10.1016/j.bbi.2022.08.004. Epub 2022 Aug 8.
Sleep disturbance, including poor subjective sleep quality and insomnia disorder, is common in older adults and associated with increases in age-related morbidity risk. Accumulating evidence implicates inflammation as an underlying mechanism. In two complementary studies, we examined whether sleep disturbance is associated with activation of cellular and transcriptional mechanisms of inflammation in older adults.
Study 1 examined whether healthy older adults with poor subjective sleep quality (n = 62), compared to those with good subjective sleep quality (n = 101), differed in monocytic production of interleukin (IL)-6 and/or tumor necrosis factor (TNF)-α following stimulation with lipopolysaccharide. Study 2 examined whether older adults with insomnia disorder (n = 17), compared to those without insomnia disorder (n = 25), differed in the regulation of transcription factors (TFs) related to immune activation (i.e., nuclear factor-κB/Rel family), sympathetic nervous system (SNS) activity (i.e., cAMP-response element-binding protein), hypothalamic-pituitary-adrenal (HPA) axis activity (i.e., glucocorticoid receptor) and anti-viral responses (i.e., interferon-regulatory factor/interferon-stimulated response element) assessed in peripheral blood mononuclear cells.
In Study 1, older adults with poor subjective sleep quality, compared to those with good subjective sleep quality, showed higher percentages of stimulated monocytes producing IL-6 only (25.4 ± 16.8 % vs 20.4 ± 13.9 %; p < 0.05, η = 0.03), producing TNF-α only (37.6 ± 13.1 % vs 31.2 ± 14.3 %; p < 0.01, η = 0.05), and co-producing IL-6/TNF-α simultaneously (17.8 ± 11.7 % vs 13.9 ± 9.6 %; p < 0.05, η = 0.03). In Study 2, older adults with insomnia disorder, compared to those without insomnia disorder, showed higher TF activity related to immune activation (p's < 0.05) and SNS function (p's < 0.001), along with lower TF activity related to HPA axis function (p's < 0.05).
In older adults, poor subjective sleep quality and insomnia diagnosis are associated with increases in monocytic cytokine production and changes in TF activity related to immune activation, SNS function, and HPA axis function. Activation of markers of cellular and transcriptional inflammation might contribute to the link between sleep disturbance and age-related morbidity risk.
睡眠障碍，包括主观睡眠质量差和失眠症，在老年人中很常见，并且与与年龄相关的发病风险增加有关。越来越多的证据表明炎症是一种潜在的机制。在两项互补的研究中，我们研究了睡眠障碍是否与老年人中细胞和转录炎症机制的激活有关。
研究 1 检查了与睡眠质量良好的老年人（n=101）相比，睡眠质量差的健康老年人（n=62）在经过脂多糖刺激后，单核细胞产生白细胞介素（IL）-6 和/或肿瘤坏死因子（TNF）-α 的情况是否不同。研究 2 检查了与没有失眠症的老年人（n=25）相比，患有失眠症的老年人（n=17）在与免疫激活（即核因子-κB/Rel 家族）、交感神经系统（SNS）活性（即 cAMP 反应元件结合蛋白）、下丘脑-垂体-肾上腺（HPA）轴活性（即糖皮质激素受体）和抗病毒反应（即干扰素调节因子/干扰素刺激反应元件）相关的转录因子（TF）的调节方面是否不同，这些在他们的外周血单核细胞中进行评估。
在研究 1 中，与睡眠质量良好的老年人相比，睡眠质量差的老年人产生 IL-6 的刺激单核细胞百分比更高（25.4±16.8% vs 20.4±13.9%；p<0.05，η=0.03），产生 TNF-α 的刺激单核细胞百分比更高（37.6±13.1% vs 31.2±14.3%；p<0.01，η=0.05），同时产生 IL-6/TNF-α 的刺激单核细胞百分比更高（17.8±11.7% vs 13.9±9.6%；p<0.05，η=0.03）。在研究 2 中，与没有失眠症的老年人相比，患有失眠症的老年人的免疫激活（p<0.05）和 SNS 功能（p<0.001）相关的 TF 活性更高，而与 HPA 轴功能相关的 TF 活性更低（p<0.05）。
在老年人中，主观睡眠质量差和失眠症诊断与单核细胞细胞因子产生增加以及与免疫激活、SNS 功能和 HPA 轴功能相关的 TF 活性变化有关。细胞和转录炎症标志物的激活可能是睡眠障碍与与年龄相关的发病风险之间的联系的原因之一。
