Published online 22 October 2001. doi:10.1083/jcb1553rr1
© The Rockefeller University Press,
0021-9525/2001/10/324 $5.00
The Journal of Cell Biology, Volume 155, Number 3, October 29, 2001 324-324
Old cells gone bad
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Epithelial cells (purple) grow on senescent (right) but not nonsenescent (left) cells.
Campisi/NAS
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The rising incidence of senescent cells during aging may promote cancer development, according to Judith Campisi (Lawrence Berkeley National Laboratory, Berkeley, CA) and colleagues. They propose that evolution may have selected a useful function for cellular senescence early in life—the switching-off of cells that are prone to becoming cancerous—without any consideration of how these cells might behave later on in life.It is not the senescent cells themselves that become cancerous, however. Rather, these fibroblast cells produce soluble factors, matrix, and perhaps cell-surface molecules that cause cocultured preneoplastic or neoplastic epithelial cells to proliferate and form tumors in nude mice. Cocultured primary epithelial cells are not affected.
The effect on proliferation may be an unwanted byproduct of the senescence expression program, which includes increased levels of an odd mixture of molecules. Only a few of these molecules are involved in cell cycle arrest, but a number may promote epithelial proliferation.
Campisi says that the expression mix may have arisen when evolution co-opted an existing program involved in wound healing to shut down the cell division of senescent fibroblasts. Wounding eventually blocks fibroblast division, as is required during senescence, but it also results in production of matrix remodeling enzymes (to clear up the mess), cytokines (to recruit macrophages), and epithelial growth factors (to close the wound). These same factors, produced in increasing amounts by increasing numbers of senescent cells, may promote the development of epithelial cancers, which constitute the vast majority of late-onset cancers in humans. 
Reference:
Krtolica, A., et al. 2001. Proc. Natl. Acad. Sci. USA. 98:12072–12077.[Abstract/Full Text]
William A. Wells
wellsw{at}rockefeller.edu
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