Cellular Aging: Telomeres

The observations discussed above clearly linked telomeres to the ability of cells to divide and proliferate. Simultaneously with these studies, and key to the development of the telomere hypothesis of cellular aging, the link between telomere stabilization and tumorigenesis was becoming clear. One feature of tumor cells is their unlimited cell-division potential, or immortality. It was first reported in 1990 that telomeres were shorter in tumors than in adjacent healthy tissue from the same individual. These observations prompted the suggestion that the cell divisions leading to tumor formation resulted in telomere loss. However, telomere length in tumor-derived cell lines remain stable over time in culture, despite continuing cell division. This observation indicated that cells that have transformed and become tumors have some means of overcoming the end-replication problem. The obvious candidate for achieving stabilization of telomeric DNA was telomerase. Studies in the early 1990s did, in fact, suggest that this enzyme was active in some tumors and immortal cell Lines. However, these studies were hampered by the lack of sensitivity of the assay used to detect telomerase.

A highly sensitive assay to detect telomerase activity was developed in 1994, and shortly thereafter, surveys of cell lines and tumors were begun to determine if telomerase activity was a common feature. The unambiguous results were that the majority (80–90 percent) of all human tumors, as well as the majority of immortal transformed cell lines, contain telomerase activity. One implication is that telomerase activation would stabilize telomere length and allow the cell to circumvent cellular senescence. However, the timing of telomerase activation during tumori-genesis is unclear, and some discussions suggest that this may occur after at least a transient abolition of telomere function (see below). These observations, together with the links between telomeres and cellular senescence, have provoked the suggestion that telomere length might act as a tumor suppressor mechanism by limiting the number of divisions any given cell might undergo.