Cancer as “Rejuvenescence”

A bstract : Comparative analysis of malignant and senescent cells shows that their phenotypic features are in many instances contrary. Cancer cells do not “age”; their metabolic and growth characteristics are opposite to those observed with cellular aging (both replicative and functional). In many such characteristics, cancer cells resemble embryonic cells. One can say that cancer manifests itself as a local uncontrolled “rejuvenation” in an organism. Available evidence from human and animal studies suggests that the opposite phenotypic features of aging and cancer arise from the opposite regulation of common genes, such as those participating in apoptosis/growth arrest or in growth signal transduction pathways in the cell. For instance, in aging cells and organisms, proto‐oncogenes are often downregulated, while tumor suppressors are permanently expressed. In cancer cells the situation is just the opposite: the proto‐oncogenes are commonly overexpressed, while tumor suppressors are downregulated. This fact may have various applications for the development of new antiaging and anticancer treatments. First, genes that are oppositely regulated in cancer and aging could be candidate targets for antiaging interventions. Their “cancerlike” regulation, if strictly controlled, might help to rejuvenate the aging organism. Recent evidence from human and animal studies in support of this view is discussed. Second, the fact that cancer cells do not “age” implies that these cells may have a survival advantage in the surrounding of senescent cells. This could be a partial reason for an increase in the risk of cancer with age, because the proportion of senescent cells increases in an organism with age, too. In such a situation, the rejuvenation of normal cells surrounding the tumor might be a perspective anticancer treatment. For instance, a controlled activation of oncogenes in normal host cells or the grafting of young proliferating cells (such as embryonic stem cells) in the area near a malignant tumor might help to supplant cancer cells rather than to kill them.