Blood tells old stem cells how to act young
Tuesday, February 02, 2010
Joslin scientists, led by Principal Investigator Amy J. Wagers, Ph.D., have uncovered exciting clues toward treating age-related conditions via the blood.
As you age, your blood ages, Dr. Wagers notes. Deep in your bone marrow, blood stem cells keep churning out your blood cells, but the mix of blood cell types goes awry, making you more prone to disease.
Researchers in her lab now have demonstrated that in old mice exposed to certain factors that are present in blood of young mice, old blood stem cells begin to act more like young ones—and this process is driven by signals from another type of cell nearby in the bone.
These results were published on January 28 in Nature, one of the world’s most prestigious journals of biomedical research.
Scientists already knew that the decline in blood stem cell function that comes with age is partly intrinsic to the cells themselves. However, these cells also are affected by signals from other cells nearby in the local bone marrow microenvironment or “niche”.
In an earlier study, Shane Mayack, Ph.D., a postdoctoral fellow in the Wagers lab, and co-workers, pinpointed bone-forming cells known as osteoblasts as key players in this signaling, with a critical role in blood stem cell maintenance and regeneration.
In their Nature paper, Dr. Mayack and her colleagues studied the blood stem cell aging process in young and old mice. The researchers found that as osteoblasts age, they change the signals that they send to stem cells, and this change makes those stem cells less able to produce the right mixture of blood cells.
More dramatically, in tests in which two mice shared a common blood circulation, the scientists revealed that this aging mechanism could be reversed. In old mice paired with young mice, the existing populations of osteoblasts showed signs of rejuvenation. Remarkably, so did the existing stem cells, so that aged mice began to exhibit much more “youthful” blood-forming abilities.
“What’s most exciting is that the changes that occur in blood stem cells during aging are reversible, through signals carried by the blood itself,” says Dr. Wagers. “This means that the blood system offers a potential therapeutic avenue for age-related stem cell dysfunction.”
While the work does not directly address diabetes mechanisms, she points out that “there’s more and more evidence of an overlap in the molecular pathways that are implicated in aging and in type 2 diabetes.”