Telomere

The search for the molecular counting mechanism ended when Calvin Harley and Carol Greider discovered that the telomeres of cultured normal human fibroblasts become shorter each time the cells divide. When telomeres reach a specific short length, they signal the cell to stop dividing. Therefore, cellular aging, as marked by telomere shortening, is not based on the passage of time. Instead, telomere loss measures rounds of DNA replication. For this reason, Hayflick has coined the term "replicometer" for this mechanism.

An accumulation of evidence suggests that while telomere attrition explains the loss of replicative capacity in normal cells, the process may not be as simple as first believed. There are several essential DNA-binding proteins (for example, TRF1 and TRF2) associated with telomeres, and the role that they play in capping and uncapping the telomere ends undoubtedly will be found to complicate the oversimplified explanation given above.