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Third Public Conference: Cellular Aging
and Apoptosis Cancer, Aging and the Double-edged Sword of Cellular Senescence Speaker The conventional wisdom holds that cancer cells are dangerous because they refuse to become senescent and die on schedule, and that normal cells are good because they turn senescent when they should and don't hang around to become malignant. As sensible as this sounds, there is mounting evidence that too much senescence may be as bad as too little in terms of promoting tumor growth. Dr. Campisi and her colleagues study the pros and cons of senescence at the Lawrence Berkeley National Laboratory in California, where she is Senior Scientist and Head of the Center for Research and Education in Aging. Earlier, she was on the faculty of the Boston University Medical School. Dr. Campisi received her Ph.D. from the State University of New York at Stony Brook and conducted her postdoctoral research with Arthur Pardee at Harvard Medical School. She has received a number of awards for her work on the relationship between aging and cancer. Topic Epidemiologists and practicing physicians have long noted that cancer rates soar in people over 50, an observation usually attributed to the build-up of deleterious genetic mutations with age. But Dr. Campisi puts at least part of the blame on the accumulation of cells with a senescent phenotype, which hang around in certain tissues long after they've undergone changes in morphology, behavior and function. They secrete many different molecules, some of which appear to have a "field effect" that promotes malignant changes in nearby cells. Support for this idea comes from a series of experiments in which preneoplastic epithelial cells were grown either on a lawn of presenescent stromal cells or one where 10-15% of cells were senescent. Dr. Campisi and her colleagues saw significantly more premalignant changes in cells exposed to senescent neighbors. The investigators obtained similar results in nude mice, where they observed a direct relationship between exposure to senescent cells and the size and number of tumors that developed. In mice, a neoplastic mutation was needed as a starting point for oncogenesis; after that, senescence appeared to drive tumor development. Dr. Campisi speculates that cellular senescence evolved as a cancer
suppression mechanism at a time when the life expectancy for humans
was far shorter than it is today. Now that people live so much longer,
senescence may be an example of antagonistic pleiotropy: a trait selected
to optimize fitness early in life turns out to have unselected deleterious
effects later on. Although this may sound like depressing news, Dr.
Campisi sees it differently. She believes that additional research will
discover small molecules that can counteract damaging secretions from
old cells that have overstayed their welcome.
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