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Fox Chase Cancer Center scientists discover key proteins linked to aging and cancer

Fox Chase Cancer Center researchers have made new discoveries that shed new light on the mystery of why human tissues, such as skin, age. The findings focus on the composition and assembly of key chromosomal protein complexes involved in shutting down reproduction of aging cells. The report by molecular and cell biologist Peter D. Adams, Ph.D. and his colleagues appears in the January 2005 issue of Developmental Cell.

"In the lab, aging cells are called senescent cells. Senescent cells are no longer able to divide but remain metabolically active," Adams explained. "Accumulation of senescent cells over time appears to contribute to changes in tissue form and function commonly associated with aging, like the skin changes that occur between childhood and old age."

Most normal human cells undergo a limited number of cell divisions but are eventually arrested, either through final differentiation or senescence. Differentiation is the process whereby a proliferating cell stops growing and develops into a cell with a specific function, such as a liver cell or a neuron. Senescence is an irreversible stage in a cell's life cycle and may underlie the human aging process and have an impact on diseases of aging, such as adult cancers.

"Most importantly, the failure of cells to stop growing through differentiation or senescence can lead to the uncontrolled growth of cancer," Adams emphasized. Both senescence and differentiation involve reorganization of chromatin structure --the complex of DNA, RNA and proteins, called histones, in the cell nucleus.

Previous research has shown that as cells reach senescence, a change in chromatin structure, called SAHF (senescence-associated heterochromatin foci), silences the genes that promote the cells' growth. Adams' discovery reveals the mechanism of SAHF formation. SAHF are domains of densely packed chromatin that repress activity of the genes that normally drive cell proliferation. Adams and coworkers have i
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Contact: Karen C. Mallet
karen.mallet@fccc.edu
215-728-2700
Fox Chase Cancer Center
3-Jan-2005


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