PQB - 4 What mechanisms of aging, beyond the accumulation of mutations, promote or protect against cancer development? Background: The incidence of most common adult cancers increases with age; however, beyond the accumulation of mutations and changes in telomere length in dividing cells, we know little about how aging affects cancer development. While it is generally true that cancer is a disease of aging, this simple statement hides many complicating features. Tumor incidence at most sites shows a peak at particular stages of life; some cancers have highest rates in early adulthood, while others have rates that continue to rise until the seventies or eighties but then decrease with advanced age. The stochastic accumulation of mutations or the shortening of telomeres seems unlikely to account for these differences over time or between tissues. This question seeks thoughtful approaches and new concepts about how changes in aging contribute to increases and decreases in cancer rates at specific sites and over time. Feasibility: Some of the basic biological processes that control aging have been described, and our knowledge of the molecular drivers of aging continues to improve. To consider causal events that alter cancer incidence rates, it seems likely that mouse or other genetic models that show these changes might provide useful systems to study aging. Similarly, physiological comparisons of tissues undergoing various stages of aging may give clues as to underlying differences in tissues, or the changing microenvironments that support tumor development might be linked to changing rates of cancer incidence. Likewise, molecular profiles of related tumors that occur at characteristically different life stages may show distinct patterns that could point to some of the variables that control how tumor incidence can be linked to the properties of aging tissues. Implications of success: Understanding which features of aging alter the rate of tumor incidence promises to identify potential biological processes that could be targets for prevention and therapy. Deeper knowledge of the molecular links between aging and cancer incidence can also identify new markers for early diagnostic tests and risk assessment. |
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