Telomeres shortening during proliferation of many cell lines can not be explained completely by the mechanism of the end replication problem. Under 40% oxygen partical pressure, cell proliferation is blocked and the rate of telomere shortening is increased. Blocked cells present senescent characteristics and accumulated single-strand breaks in telomeres. It might be speculated that accumulation of single-strand breaks and resultant loss of distal single-stranded fragments during replication could be a major cause of telomere shortening under the condition of senescence or oxidative stress. The precise mechanism of the positive or negative regulation on the telomere length by telomerase and reactive oxygen species still remains unclear.