The role of aging in cancer is studied by cloning and characterizing genes involved in cellular aging. Unlike tumor cells, normal cells have a finite lifespan and enter a state of irreversible growth arrest, termed cellular senescence, at the end of their lifespan. We have shown that cellular senescence is genetically controlled and that multiple senescence genes are altered in immortal cancer cells. Only a few senescence genes have been idnetified and efforts to clone new genes are actively being pursued. Studies of the regulation of these genes by environmental factors may elucidate the causes of aging and cancer.
Oxidative stress is a major form of endogenous and exogenous damage to cells.
A better understanding of the molecular mechanism of signal transduction leading to cell sencescence or cell death through divergent pathways is required to understand cellular responses to environmental stresses, particularly oxidative damage. As cells progress to cancer, their responses to apoptotic signals change. Cancer cells die at a higher rate than normal cells, suggesting that environmental modulators of apoptosis can influence the rate of tumor growth. One example of this is dietary restriction of animals, which reduces cancer progression by stimulating apoptosis of precancerous cells. We have shown that this is in part due to modulation by dietary restricition of circulating IGF1 levels, which blocks apoptosis of cancer cells.