DNA Damage, Cancer, and Aging

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A short open access paper: "Defects in the DNA damage response often lead to an increased susceptibility to cancer, and so the DDR presents an interesting set of novel therapeutic targets. The maintenance of genomic integrity by the DDR has also been found to be involved in the process of organismal ageing. While the removal of cells containing damaged DNA can be beneficial in the prevention of cancer, it may contribute to both normal and pathological ageing. ... Given the frequency at which DNA lesions occur (approximately 10^4 per cell per day), a complex system of damage detection and repair is required in order to preserve the integrity of the genome. This system is termed the DNA damage response (DDR), and encompasses: the recognition of DNA damage; the transduction of signals through appropriate pathways; and the activation of cellular responses ranging from DNA repair and chromatin remodeling to the activation of cell death if the damage is irreparable. ... The maintenance of the DDR is essential for faithful replication of the genome, and so is critical for cellular survival. The loss of certain DDR components can lead to an increased susceptibility to cancer due to the ensuing genomic instability and the subsequent mutation to genes required for cellular replication and division. The DDR is also involved in the induction of senescence and apoptosis when the damage cannot be repaired. While this can prolong longevity during early stages of life due to the suppression of tumorigenesis, it may become detrimental in ageing due to the loss of stem and progenitor cells for renewal. This is a phenomenon referred to as antagonistic pleiotropy, and it highlights the importance of carefully balanced cell signaling cascades and regulatory systems in the maintenance of survival. Further studies of the roles of DDR-associated proteins, along with the discovery of new ones, will therefore not only enhance our understanding of cancer and mechanisms to treat it, but will also enhance our understanding of the ageing process. This may uncover ways to treat premature ageing or other age-related pathologies, such as the decline of the immune system in the elderly."

Link: http://www.impactaging.com/papers/v2/n12/full/100248.html