June 28, 2005
Bone Marrow Stem Cell Aging Increases Leukemia And Infection Risks

When bone marrow stem cells age they divide more slowly and express some of the genes which are seen turned on in leukemia.

STANFORD, Calif. – Older people are more prone to infections and have a higher risk of developing leukemia, and now researchers at Stanford University School of Medicine have one hint as to why that may be. The group found that in mice, the bone marrow stem cells responsible for churning out new blood cells slow down in their ability to produce immune cells, leaving older mice with fewer defenses against infection.

This result is not the least bit surprising. The decrease in the ability to divide probably happens in every stem cell type in the body as animals and humans age.

These new findings, published in the June 20 online issue of Proceedings of the National Academy of Sciences, add to mounting evidence that many pitfalls of aging result from either older stem cells or stem cells responding to their older environment.

“Aging results in a diminished capacity of the body to maintain tissue and organ function. Since we know the cells mediating this maintenance are stem cells, it doesn’t take a great leap of faith to think that stem cells are at the heart of that failure,” said Derrick Rossi, PhD, postdoctoral scholar and co-first author on the paper with postdoctoral scholar David Bryder, PhD.

In addition to producing fewer immune cells, the older blood-forming stem cells were actively using genes known to be involved in leukemia, a group of cancers that affect blood cells. This could be one reason why older people are more prone to developing certain forms of leukemia.

The role of stem cells in cancer formation is suspected in a number of cancer types. Stem cells divide a lot and cell division is an error-prone process. As compared to cell types that divide less often stem cells are at greater risk of accumulating errors in genetic and epigenetic information. Those errors increase the risk of cancer as we age.

Senior author Irv Weissman, MD, director of the Stanford Institute for Cancer and Stem Cell Biology and Medicine, said one surprise came when the group transplanted older stem cells into younger mice. Those cells continued to behave like old stem cells, producing fewer immune cells and turning on cancer-causing genes. From previous work in mouse muscle cells, he said he expected the blood-forming stem cells to resume a more youthful life once transplanted into younger mice.

This work could eventually lead to new ways of improving immune function in older people or of preventing leukemia. As one example, Weissman said that by understanding the difference between older and younger stem cells it may be possible to prompt old cells to act young again, reviving their ability to produce immune cells.

What we really need is the ability to replace aged stem cells with younger and less defective stem cells. If we could replace old stem cells we'd gain many benefits including better repair capabilities, reduced risk of cancer, and better function in systems such as the immune system that require new cells to be made to respond to constantly changing threats and conditions.

Whether rejuvenation of existing aged stem cells will turn out to be practical depends on what is causing them to act aged in the first place. If a fairly small number of types of mutations or changes in epigenetic information are causing stem cells to age then perhaps gene therapies could eventually be developed to go in and fix the mutations. But if the accumulated problematic damage involves a wider range of locations in the genome then gene therapies aimed at doing repair to individual cells would need to repair too many places and the size of the genetic programming delivered by the gene therapies might end up too large to fit in any gene therapy delivery package.

My guess: For most aged stem cell types delivery of youthful replacement stem cells will likely win out over gene therapies for stem cell rejuvenation.

Share |      Randall Parker, 2005 June 28 10:46 PM  Aging Studies

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