Somatic cells from humans and other multicellular animals divide a variable but limited number of times when cultured and then enter senescence, a state in which they are alive but no longer dividings

    Some animal cells, most notably germline cells and most cancer cells can replicate indefinitely without entering senescence and so are said to be immortal. Experiments performed by Howard Cooke in 1986 indicated that germline cells have longer telomeres than somatic cells. Cooke speculated that telomerase might not be active in normal somatic human cells. Subsequent studies confirmed Cooke's theory. Somatic cells such as fibroblasts and retinal pigment epithelial cells do not have detectable telomerase activity because they do not express the reverse transcriptase component.

    Studies by Andrea G. Bodnar and coworkers have shown that when vectors bearing genes for the telomerase reverse-transcriptase subunit are introduced into human fibroblasts or retinal pigment epithelial cells, the cells have elongated telomeres, continue to divide well beyond their normal lifespan with-out entering senescence, and appear normal when viewed under the microscope. These results establish a causal relationship between telomere shortening and cellular senescence, suggesting the existence of a “mitotic clock" that regulates telomere size. Similar conclusions have been reached by studying yeast cells, which normally have active telomerase and so do not enter a senescent state. However yeast mutants that lack either telomerase RNA or telomerase reverse transcriptase become senescent.

    As indicated above, most cancer cells have telomerase activity, which raises the possibility that telomerase may be a target for chemotherapeutic agents. However, there is also reason to suspect that telomerase will not prove to be an effective target. Maria Blascoand coworkers have used recombinant DNA techniques to construct a strain of mice that lack the telomerase RNA gene. Remarkably, mice that are homologous for the missing gene appear to be normal and fertile. Continuous inbreeding has produced six generations of the mutant mice. Moreover, somatic cells from mutant mice are readily converted to tumor cells. One must be cautious in applying the information obtained with mice to humans because mouse telomere are on average 5 to 10 times longer than human telomeres. The mutant mouse experiments raise the possibility of alternative mechanisms for maintaining telomeres such as genetic recombination.