Cellular Aging: Telomeres
Telomeres, Aging, And Cancer
The experiments described here link telomeres to two sides of a single coin: cellular mortality and immortality—or aging and cancer. The salient points with respect to cellular aging, given the assumption that replicative senescence as observed in cultured cells contributes at some level to aging, are: (1) telomeres are shorter in somatic (body) cells than in the germ line (egg and sperm), (2) telomeres are shorter in older individuals than in younger individuals, and (3) telomeres get shorter with increased number of cellular divisions undergone in culture. On the flip side of the coin, most tumors have bypassed the telomere-length-dependent limitation on cellular proliferation, usually through the activation of telomerase. Finally, stabilization of telomere length by forced expression of telomerase is sufficient to confer an unlimited division potential, or cellular immorality, while inhibition of telomerase with concomitant telomere shortening causes growth arrest in immortal cells.
There is, however, an important caveat to the arguments discussed here. As noted above, telomere length acts as a type of clock in many human cell types. However, there are cell types that utilize some other clock mechanism to limit the number of divisions they undergo, including thyroid epithelial cells and breast epithelial cells. These cells enter replicative senescence while still having telomeres of sufficient length for many more divisions. Furthermore, simple expression of telomerase is not sufficient to confer immortality on these cell types. It is believed that even these cells, given circumvention of their primary clock, eventually become dependent on telomere length for continued division. The observation that most human tumors, including thyroid and breast tumors, have telomerase activity and stable telomeres would support this idea. Thus, the cumulative data indicate a key role for telomeres in the processes of cellular senescence and tumorigenesis.
DOMINIQUE BROCCOLI
See also CANCER BIOLOGY; DNA DAMAGE AND REPAIR; GENETICS: LONGEVITY ASSURANCE; THEORIES OF BIOLOGICAL AGING.
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Additional topics
Medicine EncyclopediaAging Healthy - Part 1Cellular Aging: Telomeres - Telomeres Are Chromosome Caps, Telomere Structure, Telomeres And Replication, Telomeres And Replicative Senescence, Telomeres And Premature Aging Syndromes