Normal telomere erosion rates at the single cell level in Werner syndrome fibroblast cells

摘要

The aim of this study was to investigate whether the accelerated replicative senescence seen in Werner syndrome (WS) fibroblasts is due to accelerated telomere loss per cell division. Using single telomere length analysis (STELA) we show that the mean rate of telomere shortening in WS bulk cultures ranges between that of normal fibroblasts [99 bp/population doubling (PD)] and four times that of normal (355 bp/PD). The telomere erosion rate in the fastest eroding strain slows in the later stages of culture to that observed in normal fibroblasts, and appears to be correlated with a reduction in the heterogeneity of the telomere-length distributions. Telomere erosion rates in clones of WS cells are much reduced compared with bulk cultures, as are the variances of the telomere-length distributions. The overall lack of length heterogeneity and the normal erosion rates of the clonal populations are consistent with simple end-replication losses as the major contributor to telomere erosion in WS cells. We propose that telomere dynamics at the single cell level in WS fibroblasts are not significantly different from those in normal fibroblasts, and suggest that the accelerated replicative decline seen in WS fibroblasts does not result from accelerated telomere erosion.