The Individual Blood Cell Telomere Attrition Rate Is Telomere Length Dependent

Abstract

Age-associated telomere shortening is a well documented feature of peripheral blood cells in human population studies, but it is not known to what extent these data can be transferred to the individual level. Telomere length (TL) in two blood samples taken at ∼10 years interval from 959 individuals was investigated using real-time PCR. TL was also measured in 13 families from a multigenerational cohort. As expected, we found an age-related decline in TL over time (r = –0.164, PPPin vivo, providing protection of short telomeres as previously demonstrated in vitro. Our findings might challenge the hypothesis that individual TL can predict possible life span or later tumor development. An age-dependent telomere shortening has been frequently observed in cross-sectional studies on human blood cells. Telomerase is an enzyme capable of lengthening telomeres, and it is activated in most tumor cells in order for them to become immortalized. This is one of the first longitudinal studies on telomere length, investigated in human blood samples taken at two occasions with approximately 10 years between them. An interesting finding was that the individual telomere length in the first blood sample was highly correlated with telomere attrition rate. Thus, individuals displaying the longest telomeres at baseline showed the most rapid telomere shortening over time and vice versa. This was also observed at the family level when exploring a multigenerational cohort. These results are in concordance with the fact that telomerase seems to preferentially act on the shortest telomeres in cultivated cells and provide fundamental knowledge for general telomere and cell biology. Because one part of the cohort developed tumors after the second blood draw, we had the opportunity to examine whether telomere attrition rate differed in tumor patients compared with controls, but no such indication was observed. However, for prostate cancer, short telomere length ≥9 years before diagnosis seemed to predict death.