National Institute for Public Health and the Environment, Bilthoven, the Netherlands; Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, the Netherlands.
Department of Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, the Netherlands.
Exp Gerontol. 2019 Oct 1;125:110674. doi: 10.1016/j.exger.2019.110674. Epub 2019 Jul 20.
With aging, the human immune system undergoes several changes. The clinical relevance of these changes, however, is relatively unknown. We investigated immunological aspects of human aging in relation to frailty in the Doetinchem Cohort Study (DCS).
We calculated a frailty index score based on 36 health parameters for each individual in the DCS with data obtained in the period 2008-2016. The frailty index was used to define three health groups ('healthy', 'intermediate', and 'frail'), stratified by age and sex. In a subcohort (n = 289, 60-85 years, selected by balanced random sampling per frailty group), we collected blood samples between October 2016 and March 2017 to determine absolute numbers of leukocyte subsets. In addition, cytomegalovirus serostatus was assessed. C-reactive protein (CRP) levels were longitudinally assessed in four consecutive plasma samples per individual. These samples had been previously collected (1993-2013) as part of the DCS at regular time intervals and spanning a period of >15 years.
We observed higher numbers of myeloid derived neutrophils and monocytes in the frail group compared to the healthy group in both men and women, and, retrospectively, consistently higher CRP concentrations over a period of >15 years. An increase in CRP concentration with age was found in women, but not in men. Frailty was not associated with cytomegalovirus serostatus or with changes in lymphoid derived T-, B-, or NK-cell numbers.
Frail elderly, compared to their age- and sex-matched peers, endure a chronic and stable low-grade inflammation, which is associated with a myeloid cell lineage expansion. These findings could help to monitor clinically significant immunological decline in the elderly.
随着年龄的增长，人体免疫系统会发生多种变化。然而，这些变化的临床意义尚不清楚。我们在多庭特恩科赫特队列研究（DCS）中研究了与虚弱相关的人类衰老的免疫学方面。
我们根据 DCS 中 2008-2016 年获得的数据，为每个个体计算了一个基于 36 个健康参数的虚弱指数评分。虚弱指数用于根据年龄和性别定义三个健康组（“健康”、“中等”和“虚弱”）。在一个亚队列中（n=289，年龄在 60-85 岁之间，按每个虚弱组的平衡随机抽样选择），我们于 2016 年 10 月至 2017 年 3 月间采集血液样本，以确定白细胞亚群的绝对数量。此外，还评估了巨细胞病毒血清状态。对每位个体的四个连续血浆样本进行了 C 反应蛋白（CRP）水平的纵向评估。这些样本是作为 DCS 的一部分在定期时间间隔内采集的，从 1993 年至 2013 年跨越了 >15 年的时间。
我们观察到男性和女性中，虚弱组的髓系衍生中性粒细胞和单核细胞数量高于健康组，并且在 >15 年的时间里，回溯性地观察到 CRP 浓度始终较高。女性中 CRP 浓度随年龄增加而增加，但男性中没有。虚弱与巨细胞病毒血清状态或淋巴系衍生 T、B 或 NK 细胞数量的变化无关。
与年龄和性别匹配的同龄人相比，虚弱的老年人承受着慢性且稳定的低度炎症，这与髓系细胞系扩张有关。这些发现有助于监测老年人临床显著的免疫衰退。
