Telomere biology in aging and cancer.
It is thought that a limited investment by the body in many types of maintenance and repair causes aging. Cell turnover is one mechanism of replacing damaged cells, and cell division thus contributes to good repair, but the number of times cells can divide is limited to form a barrier against cancer. Precancerous cells must divide many times to accumulate all of the mutations needed to become malignant. Limiting the number of times they can divide helps prevent cancer. The mechanism for counting cell divisions lies in structures at the ends of the chromosomes called telomeres that shorten with every division, eventually causing cell aging. This shortening can be prevented and cells immortalized using the enzyme telomerase, which can elongate telomeres. Immortalizing all of the cells in the body might increase repair but would remove the barrier to malignancy and would probably cause premature death from cancer in many cases, although the ability to immortalize cells opens up enormous opportunities for using normal cells for therapeutic purposes in localized areas. Eventually, once better controls and treatments for cancer are available, cellular rejuvenation by manipulating telomeres may reduce some of the physiological declines that accompany aging. Such treatments should increase health span, but because replicative aging represents only one of many processes that may contribute to overall human aging, modest increases in life span are expected at best.
Wright
Woodring E
WE
Department of Cell Biology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Building K2.206, MC 9039, Dallas, TX 75235, USA. woodring.wright@utsouthwestern.edu
Shay
Jerry W
JW
D000375:Aging / Q000235:genetics* / Q000502:physiology; D000818:Animals; D001695:Biology; D002455:Cell Division / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D008136:Longevity / Q000235:genetics; D009369:Neoplasms / Q000235:genetics*; D012060:Rejuvenation / Q000502:physiology; D019098:Telomerase / Q000502:physiology; D016615:Telomere / Q000235:genetics / Q000502:physiology*
D019098:Telomerase