Telomeres and Cell Division

Certain types of cells can be removed from the body and grown in nutrient solutions (outside the body, or in vitro). Under these artificial conditions, the potential longevity of different cell lines can be studied. For unknown reasons, normal connective tissue cells (called fibroblasts) stop dividing in vitro after a certain number of population doublings. Cells from a newborn will divide 80 to 90 times, while those from a 70-year-old will stop after 20 to 30 divisions. The decreased ability to divide is thus an indicator of senescence (aging). Cells that become transformed into cancer, however, apparently do not age and continue dividing indefinitely in culture.

This senescent decrease in the ability of cells to replicate may be related to a loss of DNA sequences at the ends of chromosomes, in regions called telomeres (from the Greek telos = end). The telomeres serve as caps on the ends of DNA, preventing enzymes from mistaking the normal ends for broken DNA and doing damage by trying to "repair" them.

The DNA polymerase enzyme does not fully copy the DNA at the end-regions. Each time a chromosome replicates, it loses 50 to 100 base pairs in its telomeres. Cell division may ultimately stop when there is too much loss of DNA in the telo-meres, and the cell dies because of damage it sustains in the

Telomere And Dolly Sheep

Cell Structure and Genetic Control 75

course of aging. Interestingly, Dolly (the famous cloned sheep) had short telomeres, because her DNA was older than she was. For reasons not presently clear, however, cloned cattle seem to have long telomeres, despite the short telomeres of the donors. Will Dolly's life be shorter and the cloned cattle's longer because of this? It is too soon to tell.

Germinal cells that give rise to gametes (sperm cells and ova) can continue to divide indefinitely, perhaps because they produce an enzyme called telomerase, which duplicates the telomere DNA. Telomerase is also found in hematopoietic stem cells (those in bone marrow that produce blood cells) and other stem cells that must divide continuously. Similarly, telomerase is produced by most cancer cells, and there is evidence to suggest that telomerase may be responsible for their ability to divide indefinitely.

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