Lower red blood cell counts in middle-aged subjects with shorter peripheral blood leukocyte telomere length

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.