Lustig Ana, Liu Hans B, Metter E Jeffrey, An Yang, Swaby Melissa A, Elango Palchamy, Ferrucci Luigi, Hodes Richard J, Weng Nan-Ping
Laboratory of Molecular Biology and Immunology, National Institute on Aging, National Institutes of Health, Baltimore, MD, United States.
Department of Neurology, University of Tennessee Health Science Center, Memphis, TN, United States.
Front Immunol. 2017 Aug 24;8:1027. doi: 10.3389/fimmu.2017.01027. eCollection 2017.
A number of biological parameters have been cited as hallmarks of immune aging. However, it is not clear whether these multiple biological changes are the result of common underlying aging processes and follow correlated trajectories, or whether the patterns of change for multiple parameters vary across individuals and reflect heterogeneity in the aging process. Here, we have studied parameters of immune system aging through longitudinal analysis of telomere length, inflammatory cytokines, and antibody titer to cytomegalovirus (CMV) in 465 subjects ranging in age from 21 to 88 years at the first visit, with an average of 13 years (7-19 years) follow-up. We observed a highly variable rate of change in telomere length of PBMCs with a relatively slow average rate of telomere shortening (-16 bp/year). Similarly, there were significant increases with age in three inflammation-related cytokines (interferon gamma, IL-6, and IL-10) and in anti-CMV IgG titer, which varied widely across individuals as well. We further observed positive correlative changes among different inflammatory cytokines. However, we did not find significant correlations among the rate of changes in telomere length, inflammatory cytokines, and anti-CMV IgG titers. Our findings thus reveal that age-related trajectories of telomere attrition, elevated circulating inflammatory cytokines, and anti-CMV IgG are independent and that aging individuals do not show a uniform pattern of change in these variables. Immune aging processes are complex and vary across individuals, and the use of multiple biomarkers is essential to evaluation of biological aging of the immune system.
许多生物学参数已被视为免疫衰老的标志。然而,尚不清楚这些多种生物学变化是常见潜在衰老过程的结果并遵循相关轨迹,还是多个参数的变化模式在个体间存在差异并反映了衰老过程中的异质性。在此,我们通过对465名受试者进行纵向分析,研究了免疫系统衰老的参数,这些受试者首次就诊时年龄在21至88岁之间,平均随访13年(7至19年)。我们观察到外周血单核细胞(PBMC)端粒长度的变化率高度可变,平均端粒缩短速率相对较慢(-16 bp/年)。同样,三种与炎症相关的细胞因子(干扰素γ、白细胞介素-6和白细胞介素-10)以及抗巨细胞病毒(CMV)IgG滴度也随年龄显著增加,个体间差异也很大。我们进一步观察到不同炎症细胞因子之间存在正相关变化。然而,我们未发现端粒长度变化率、炎症细胞因子和抗CMV IgG滴度之间存在显著相关性。因此,我们的研究结果表明,端粒损耗、循环炎症细胞因子升高和抗CMV IgG的年龄相关轨迹是独立的,衰老个体在这些变量上并未表现出统一的变化模式。免疫衰老过程复杂且个体间存在差异,使用多种生物标志物对于评估免疫系统的生物衰老至关重要。