Adding More Data to the Role of Nuclear DNA Damage in Aging

We accumulate random nuclear DNA damage - mutations - as we age. This is understood to increase the risk of cancer, as the more mutations that occur the greater the chance that one will be of the rare type that can spawn a cancer, but there is some debate over the degree to which nuclear DNA damage contributes to aging itself. Here researchers add some more data to the picture: "Hundreds of mutations exist in leukemia cells at the time of diagnosis, but nearly all occur randomly as a part of normal aging and are not related to cancer, new research shows. [Researchers] have found that even in healthy people, stem cells in the blood routinely accumulate new mutations over the course of a person's lifetime. And their research shows that in many cases only two or three additional genetic changes are required to transform a normal blood cell already dotted with mutations into acute myeloid leukemia (AML). ... The study is the first to investigate how often mutations typically develop in healthy stem cells in the blood. ... In recent years, [researchers] have sequenced the genomes of 200 patients with AML to try to understand the mutations at the root of the disease. Without fail, each patient's leukemia cells held hundreds of mutations, posing a conundrum for scientists, who have long believed that all the mutations in a cancer cell are likely to be important for the disease to progress. ... But we knew all of these mutations couldn't be important. It didn't make any sense to us that so many mutations were present in all the cells in the tumor. ... Every person has about 10,000 blood stem cells in their bone marrow, and the researchers found that each stem cell acquires about 10 mutations over the course of a year. By age 50, a person has accumulated nearly 500 mutations in every blood stem cell. ... Mutations are known to develop in cells as we age, but no one had any idea how many mutations occur in blood stem cells and how frequently they develop. These random, background mutations occur during cell division and are unrelated to cancer. Our DNA can tolerate a huge number of these hits without any negative consequences. But if a cancer-initiating event occurs in one of these stem cells, it captures the genetic history of that cell, including the earlier mutations, and drives leukemia to develop. ... scientists were surprised to see that the total number of mutations varied by age, not by whether a patient had leukemia. Thus, a healthy person in his 40s had just about the same number of mutations in his blood stem cells as a leukemia patient of the same age had in his cancer cells."

Link: http://www.sciencedaily.com/releases/2012/07/120719132606.htm

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