STANFORD, Calif. -- As stem cells in the blood grow older, genetic mutations accumulate that could be at the root of blood diseases that strike people as they age, according to work done in mice by researchers at the Stanford University School of Medicine.

"This and our previous work points out why older people are more likely to get blood diseases, such as leukemia or anemia, and are less likely to make new antibodies that would protect against infections like the flu," said senior author Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative Medicine and of the Stanford Comprehensive Cancer Center. The work will be published in the June 6 issue of Nature.

In past studies, this group of researchers had shown that blood-forming stem cells in the bone marrow of mice became less able to divide and replenish the supply of blood cells as they aged. The question was why.

Researchers have put forward many theories about how cells age, said Derrick Rossi, PhD, postdoctoral scholar and co-first author of the paper. One of those theories has to do with cells accumulating genetic mutations. "The idea is that, over time, accumulated DNA damage progressively diminishes the cell's ability to perform its normal function," he said.

However, researchers had thought that mutations were unlikely to underlie aging in blood-forming stem cells because they very rarely divide, and most mutations crop up during division. The infrequent divisions were believed to protect the cells from acquiring new mutations.

Rossi, Weissman and the other first author, postdoctoral scholar David Bryder, PhD, tested that idea in two different sets of experiments. In the first, they studied the blood-forming stem cells of mice engineered to have single mutations that make them especially prone to accumulating additional genetic errors. In each o
'"/>

Contact: Amy Adams
amyadams@stanford.edu
650-723-3900
Stanford University Medical Center
6-Jun-2007