Telomere shortening is proportional to the size of the G-rich telomeric 3 '-overhang

Most normal diploid human cells do not express telomerase activity and are unable to maintain telomere length with ongoing cell divisions. We show tha t the length of the single-stranded G-rich telomeric 3'-overhang is proport ional to the rate of shortening in four human cell types that exhibit diffe rent rates of telomere shortening in culture. These results provide direct evidence that the size of the G-rich overhang is not fixed but subject to r egulation. The potential ability to manipulate this rate has profound impli cations both for slowing the rate of replicative aging in normal cells and for accelerating the rate of telomere loss in cancer cells in combination w ith anti-telomerase therapies.