[[Cancer and aging--biological mechanisms]

Aging is the major risk factor for the development of cancer. An understanding of the molecular mechanisms that induce cancer formation during aging could help to develop cancer prevention strategies and improve cancer screening in the elderly. On the cellular level, it is of utmost importance to decipher molecular alterations leading to dysfunction and transformation of adult stem cells, since there is growing evidence that stem cells acquire the initial lesions that ultimately lead to cancer formation. On the molecular level, the accumulation of DNA damage and chromosomal instability represents a hallmark feature of cancer development in aged tissues. Different mechanisms can contribute to an accumulation of DNA damage and chromosomal instability during aging, including (i) telomere shortening, (ii) a reduction in DNA repair capacity, and (iii) the declining function of checkpoints (e. g. senescence, apoptosis). In addition, alterations in the cell environment can increase the selection of (pre-)malignant clones in aging tissues, involving (i) the loss of proliferative competition of non-transformed organ cells, (ii) the aberrant production of cytokines and growth factors, (iii) an impaired immune surveillance. In this review, we summarize experimental data on the functional role of these different mechanisms increasing the cancer risk during tissue aging.