Bekaert Sofie, De Meyer Tim, Rietzschel Ernst R, De Buyzere Marc L, De Bacquer Dirk, Langlois Michel, Segers Patrick, Cooman Luc, Van Damme Piet, Cassiman Peter, Van Criekinge Wim, Verdonck Pascal, De Backer Guy G, Gillebert Thierry C, Van Oostveldt Patrick
Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium.
Aging Cell. 2007 Oct;6(5):639-47. doi: 10.1111/j.1474-9726.2007.00321.x.
Evidence assembled over the last decade shows that average telomere length (TL) acts as a biomarker for biological aging and cardiovascular disease (CVD) in particular. Although essential for a more profound understanding of the underlying mechanisms, little reference information is available on TL. We therefore sought to provide baseline TL information and assess the association of prevalent CVD risk factors with TL in subjects free of overt CVD within a small age range. We measured mean telomere restriction fragment length of peripheral blood leukocytes in a large, representative Asklepios study cohort of 2509 community-dwelling, Caucasian female and male volunteers aged approximately 35-55 years and free of overt CVD. We found a manifest age-dependent telomere attrition, at a significantly faster rate in men as compared to women. No significant associations were established with classical CVD risk factors such as cholesterol status and blood pressure, yet shorter TL was associated with increased levels of several inflammation and oxidative stress markers. Importantly, shorter telomere length was associated with an increasingly unhealthy lifestyle, particularly in men. All findings were age and gender adjusted where appropriate. With these cross-sectional results we show that TL of peripheral blood leukocytes primarily reflects the burden of increased oxidative stress and inflammation, whether or not determined by an increasingly unhealthy lifestyle, while the association with classical CVD risk factors is limited. This further clarifies the added value of TL as a biomarker for biological aging and might improve our understanding of how TL is associated with CVD.
过去十年收集的证据表明,平均端粒长度(TL)可作为生物衰老尤其是心血管疾病(CVD)的生物标志物。尽管对于更深入理解潜在机制至关重要,但关于端粒长度的参考信息却很少。因此,我们试图在一个较小年龄范围内,为无明显心血管疾病的受试者提供基线端粒长度信息,并评估常见心血管疾病危险因素与端粒长度之间的关联。我们在一项大型、具有代表性的阿斯克勒庇俄斯研究队列中,测量了2509名年龄约35 - 55岁、无明显心血管疾病的社区居住白种女性和男性志愿者外周血白细胞的平均端粒限制性片段长度。我们发现端粒损耗明显与年龄相关,男性的损耗速度明显快于女性。未发现与胆固醇水平和血压等经典心血管疾病危险因素有显著关联,但较短的端粒长度与多种炎症和氧化应激标志物水平升高有关。重要的是,较短的端粒长度与越来越不健康的生活方式有关,尤其是在男性中。所有结果在适当情况下均进行了年龄和性别调整。通过这些横断面研究结果,我们表明外周血白细胞的端粒长度主要反映了氧化应激和炎症增加的负担,无论是否由日益不健康的生活方式所决定,而与经典心血管疾病危险因素的关联有限。这进一步阐明了端粒长度作为生物衰老生物标志物的附加价值,并可能增进我们对端粒长度与心血管疾病之间关联的理解。