Chromatin: a molecular interface between cancer and aging

To prevent cancer, mammals have evolved potent tumor suppression mechanisms, including senescence and apoptosis. These processes depend on regulation of chromatin. Chromatin-dependent tumor suppressor pathways are activated in premalignant cells and tissues harboring cancer-causing genetic alterations, and also in normal aged tissue, the latter likely due to accumulation of genetic and cellular damage. Paradoxically, however, disruption of chromatin structure may also promote cancer. Apparent defects in chromatin structure accumulate with age, the biggest single risk factor for cancer. Evidence suggests that these age-associated perturbations in chromatin structure contribute to the age-associated increase in incidence of cancer. Thus, alterations in chromatin structure can both suppress and promote the onset of cancer, and both activities are inextricably linked to aging.