De Meyer Tim, De Buyzere Marc L, Langlois Michel, Rietzschel Ernst R, Cassiman Peter, De Bacquer Dirk, Van Oostveldt Patrick, De Backer Guy G, Gillebert Thierry C, Van Criekinge Wim, Bekaert Sofie
Department of Molecular Biotechnology, Faculty of Bioscience Engineering, Ghent University, Coupure Links 653, Ghent, Belgium.
Aging Cell. 2008 Oct;7(5):700-5. doi: 10.1111/j.1474-9726.2008.00419.x. Epub 2008 Jul 28.
Although telomere biology was revealed to play an important role in several hematopoietic disorders, its impact on the age-dependent dynamics of regular hematopoiesis is poorly understood. In vitro results suggest that particularly the erythropoietic capacity might be limited by critically short telomere length (TL). However, it remains unclear whether TL also affects erythropoiesis in healthy individuals in vivo. Therefore, we analyzed the associations between relevant hematopoietic parameters and peripheral blood leukocyte TL in the apparently healthy Asklepios study population, aged approximately 35-55 years (N > 2500). Our data indicate a clear positive, age and paternal age at birth adjusted, correlation between TL and red blood cell count, both in men (p < 0.001) and women (p = 0.011). This association was particularly significant in the older segment of the population (> 45 years old, both sexes: p = 0.003) and in younger men (p = 0.013), but not in younger women (p = 0.521). Further adjustment for known determinants in a general linear model revealed that peripheral blood leukocyte TL is most probably an independent predictor of red blood cell count (p < 0.001), suggesting that critical telomere shortening might also limit erythropoiesis in vivo. While negligible in a middle-aged population, the clinical consequences might be important in the elderly (e.g. in anemia of chronic disease). Further studies are required to confirm the impact of our results.
尽管端粒生物学在多种造血系统疾病中发挥着重要作用,但其对正常造血随年龄变化动态的影响却知之甚少。体外研究结果表明,尤其是红细胞生成能力可能受到极短端粒长度(TL)的限制。然而,TL在健康个体体内是否也影响红细胞生成仍不清楚。因此,我们在年龄约为35 - 55岁(N > 2500)的看似健康的阿斯克勒庇俄斯研究人群中,分析了相关造血参数与外周血白细胞TL之间的关联。我们的数据表明,在调整年龄和出生时父亲年龄后,TL与红细胞计数之间存在明显的正相关,男性(p < 0.001)和女性(p = 0.011)均如此。这种关联在人群中年龄较大的部分(> 45岁,男女均有:p = 0.003)和较年轻的男性(p = 0.013)中尤为显著,但在较年轻的女性中不显著(p = 0.521)。在一般线性模型中对已知决定因素进行进一步调整后发现,外周血白细胞TL很可能是红细胞计数的独立预测因子(p < 0.001),这表明关键的端粒缩短在体内可能也会限制红细胞生成。虽然在中年人群中影响可忽略不计,但在老年人中(如在慢性病贫血中)临床后果可能很重要。需要进一步研究来证实我们结果的影响。