Aging, tumor suppression and cancer: high wire-act!

Evolutionary theory holds that aging is a consequence of the declining force of natural selection with age. We discuss here the evidence that among the causes of aging in complex multicellular organisms, such as mammals. is the antagonistically pleiotropic effects of the cellular responses that protect the organism from cancer. Cancer is relatively rare in young mammals, owing in large measure to the activity of minor suppressor rnechanisms. These mechanisms either protect the genome from damage and/or mutations. or they elicit cellular responses-apoptosis or senescence-that eliminate or prevent the proliferation of somatic cells at risk for neoplastic transformation. We focus here on die senescence response. reviewing its causes, regulation and effects. In addition, we describe recent data that support the idea that both senescence and apoptosis may indeed be the double-edged swords predicted by the evolutionary hypothesis of antagonistic pleiotropy- protecting organisms from cancer early in life, but promoting aging phenotypes, including late life cancer. in older organisms. (C) 2004 Elsevier Ireland Ltd. All rights reserved.