Older stem cells less likely to prevent leukemia, infections
Study finds that younger bone marrow cells less susceptible to disease than those from older animals
Irving Weissman
BY AMY ADAMS
Older people are more prone to infections and have a higher risk of developing leukemia. Now researchers at the School of Medicine have one hint as to why: 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.
These 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," said Derrick Rossi, PhD, postdoctoral scholar and co-first author on the paper. "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." The other first author is 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.
Senior author Irving Weissman, MD, director of the Stanford Institute for Stem Cell Biology and Regenerative 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 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.