A View of Stochastic DNA Damage in Aging
Cancer is thought to be a disease of aging because we accumulate randomly distributed damage to nuclear DNA as we age. The older you are the more of this damage you have. Sooner or later the right combination of mutations occur in a cell that slips past the monitoring of the immune system and other defensive systems, which themselves decline with age due to other forms of damage, and it runs amok to grow a cancer. It remains an open question as to whether this nuclear DNA damage in aging is significant in any other way besides cancer over the present length of a human life span, though it is the default assumption in the research community that this is the case.
There is no good evidence, however, to show that DNA damage and only DNA damage is the cause of other meaningful changes in cellular metabolism characteristic of aging. You can of course correlate damage with progress in aging, and show that calorie restriction - to pick one example - slows the accumulation of nuclear DNA damage along with other measures of aging, but aging is a global phenomenon: these correlations don't even come close to implying direct causation. Finding a more definitive connection is an experiment that lies somewhere in the near future, enabled by more capable biotechnologies and a novel study setup devised by clever researchers.
In any case, this recent research is one narrow example of a way in which random nuclear DNA damage causes cancer - or rather more cancer in this case:
For a small percentage of cancer patients, treatment aimed at curing the disease leads to a form of leukemia with a poor prognosis. Conventional thinking goes that chemotherapy and radiation therapy induce a barrage of damaging genetic mutations that kill cancer cells yet inadvertently spur the development of acute myeloid leukemia (AML), a blood cancer. But a new [study] challenges the view that cancer treatment in itself is a direct cause of what is known as therapy-related AML. Rather, the research suggests, mutations in a well-known cancer gene, P53, can accumulate in blood stem cells as a person ages, years before a cancer diagnosis. If and when cancer develops, these mutated cells are more resistant to treatment and multiply at an accelerated pace after exposure to chemotherapy or radiation therapy, which then can lead to AML, the study indicates.The researchers initially sequenced the genomes of 22 cases of therapy-related AML, finding that those patients had similar numbers and types of genetic mutations in their leukemia cells as other patients who developed AML without exposure to chemotherapy or radiation therapy, an indication that cancer treatment does not cause widespread DNA damage. "This is contrary to what physicians and scientists have long accepted as fact. It led us to consider a novel hypothesis: P53 mutations accumulate randomly as part of the aging process and are present in blood stem cells long before a patient is diagnosed with therapy-related AML."
Researchers have known that patients with therapy-related AML are more likely than other AML patients to have a high rate of P53 mutations in their blood cells. The gene is a tumor suppressor and normally works to keep cell division in check and maintain the structure of chromosomes inside cells. But when both copies of the gene are disabled by mutations, cancer can develop. Surprisingly, when the researchers analyzed blood samples from 19 healthy people ages 68-89 with no history of cancer or chemotherapy, they found that nearly 50 percent had mutations in one copy of P53, an indicator that many people acquire mutations in this gene as they age.