Department of Psychiatry, University of California San Francisco, San Francisco, California, United States of America.
PLoS One. 2011;6(5):e19687. doi: 10.1371/journal.pone.0019687. Epub 2011 May 13.
Leukocyte telomere length (LTL) is an emerging marker of biological age. Chronic inflammatory activity is commonly proposed as a promoter of biological aging in general, and of leukocyte telomere shortening in particular. In addition, senescent cells with critically short telomeres produce pro-inflammatory factors. However, in spite of the proposed causal links between inflammatory activity and LTL, there is little clinical evidence in support of their covariation and interaction.
METHODOLOGY/PRINCIPAL FINDINGS: To address this issue, we examined if individuals with high levels of the systemic inflammatory markers interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP) had increased odds for short LTL. Our sample included 1,962 high-functioning adults who participated in the Health, Aging and Body Composition Study (age range: 70-79 years). Logistic regression analyses indicated that individuals with high levels of either IL-6 or TNF-α had significantly higher odds for short LTL. Furthermore, individuals with high levels of both IL-6 and TNF-α had significantly higher odds for short LTL compared with those who had neither high (OR = 0.52, CI = 0.37-0.72), only IL-6 high (OR = 0.57, CI = 0.39-0.83) or only TNF-α high (OR = 0.67, CI = 0.46-0.99), adjusting for a wide variety of established risk factors and potential confounds. In contrast, CRP was not associated with LTL.
CONCLUSIONS/SIGNIFICANCE: Results suggest that cumulative inflammatory load, as indexed by the combination of high levels of IL-6 and TNF-α, is associated with increased odds for short LTL. In contrast, high levels of CRP were not accompanied by short LTL in this cohort of older adults. These data provide the first large-scale demonstration of links between inflammatory markers and LTL in an older population.
白细胞端粒长度(LTL)是生物年龄的新兴标志物。慢性炎症活动通常被认为是生物衰老的促进因素,特别是白细胞端粒缩短。此外,端粒极短的衰老细胞会产生促炎因子。然而,尽管炎症活动与 LTL 之间存在因果关系的假设,但几乎没有临床证据支持它们的相关性和相互作用。
方法/主要发现:为了解决这个问题,我们研究了体内高水平的系统性炎症标志物白细胞介素 6(IL-6)、肿瘤坏死因子-α(TNF-α)和 C 反应蛋白(CRP)是否会增加端粒较短的可能性。我们的样本包括 1962 名参加健康、衰老和身体成分研究(年龄范围:70-79 岁)的高功能成年人。逻辑回归分析表明,高水平的 IL-6 或 TNF-α的个体,端粒较短的几率明显较高。此外,与既不高(OR=0.52,CI=0.37-0.72)、仅 IL-6 高(OR=0.57,CI=0.39-0.83)或仅 TNF-α高(OR=0.67,CI=0.46-0.99)的个体相比,高水平的 IL-6 和 TNF-α的个体,端粒较短的几率明显更高,调整了多种已确立的风险因素和潜在混杂因素。相比之下,CRP 与 LTL 无关。
结论/意义:结果表明,高水平的 IL-6 和 TNF-α联合作为炎症负荷的指标,与端粒较短的几率增加有关。相比之下,在这一老年人群中,高水平的 CRP 并没有伴随着端粒较短。这些数据首次大规模证明了炎症标志物与老年人 LTL 之间的联系。