engleski

The load of short telomeres, estimated by a new method, Universal STELA, correlates with number of senescent cells

Short telomeres are thought to trigger senescence, most likely through a single or a few critically shortened telomeres. Such short telomeres are thought to result from a combination of gradual linear shortening resulting from the end replication problem, reflecting the number of cell divisions, superimposed by a more stochastic mechanism, suddenly causing a significant shortening of a single telomere. Previously, studies that have tried to explore the role of critically shortened telomeres have been hampered by methodological problems. With the method presented here, Universal STELA, we have a tool that can directly investigate the relationship between senescence and the load of short telomeres. The method is a variant of the chromosome specific STELA method, but has the advantage that it can demonstrate short telomeres regardless of chromosome. With Universal STELA we find a strong correlation between the load of short telomeres and cellular senescence. We show that the load of short telomeres correlates strongly with the frequency of cells staining positive for β-Gal activity. Further we show that the load of short telomeres is higher in senescent cells compared to proliferating cells at the same passage, and that senescent cells in early passages harbor as many short telomeres as senescent cells in late passages, offering an explanation of premature cell senescence. This new method, Universal STELA, offers some advantages compared to existing methods and can be used to explore many of the unanswered questions in telomere biology including the role that telomeres play in cancer and aging.

Telomere ; aging ; cancer ; PCR ; senescence ; abrupt shortening

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