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Cellular senescence a double-edged sword
Date:12/3/2008

inflammation can also promote the development of further cancers later in life.

"Chemotherapy can cure cancer but our results suggest that this cure comes with a high cost and poses a risk that could come back to haunt the patient," Campisi said. "There is a great need for new biological therapies that more effectively exploit the specific differences between normal and cancer cells. Meanwhile, prevention remains the best treatment for cancer."

Evolutionary Implications

The findings by Campisi and her co-authors that cellular senescence can be beneficial to the young and deleterious to the old provide what may be the first molecular evidence in support of a major evolutionary theory on aging called "antagonistic pleiotropy." This theory holds that natural selection can favor a trait that contributes to early life fitness even if that trait is harmful in older individuals.

"The dynamic we have shown between the cancer prevention and aging effects of cellular senescence is an example of the trade-offs between early fitness and late life survival, exactly what is predicted by antagonistic pleiotropy," said Campisi. "The challenge now is to preserve the anti-cancer activity of cellular senescence while dampening its pro-aging effects. Although senescent cells exist for the good purpose of preventing cancer, we don't want them to hang around we want the body to be able to get rid of them."

To this end, Campisi and her colleagues are now developing mouse models through which they can determine whether there are molecular pathways by which senescent cells can either be safely expelled, or selectively destroyed.

"Senescent cells are extremely stable and do not die, therefore they accumulate in the body over time in multiple tissues," she said. "The true test as to whether cellular senescence is driving the pathologies associated with aging will come if we are able to get rid of senescent cells in our mouse mode
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Contact: Lynn Yarris
lcyarris@lbl.gov
510-486-5375
DOE/Lawrence Berkeley National Laboratory
Source:Eurekalert  

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