Stem cells don't get wrinkles, but when they're old, it shows. Precursors to blood cells—called hematopoietic stem cells (HSCs)—become sloppy at their job as they age. The result is poorer immune function, increased risk of blood cancers, and an imbalance among the types of blood cells produced. Research has suggested that some of this aging is due to HSCs’ intrinsic factors, such as DNA damage that accumulates over time. But HHMI early career scientist Amy Wagers suspected that external factors might also cause the cells to grow old, coordinating aging among organs.
“Different types of stem cells throughout the body all age together, so there could be some kind of global aging signal,” says Wagers. “Since blood has access to all organs, it made sense to look there first.”
To test whether blood could turn back the clock on stem cell function, Wagers’ lab group at Harvard Medical School turned to mice. The researchers joined the circulations of old and young mice and observed the effects on HSCs. The results were dramatic: after 4 weeks of having young blood coursing through their veins, the older mice had HSCs that numbered—and functioned—much more like their younger counterparts. By using markers that distinguished old HSCs from young ones, the researchers verified that the older cells had recovered youthful characteristics (rather than young HSCs migrating from young mice to older animals). The stem cells in the younger mice appeared unchanged.
Wagers hypothesized that osteoblastic niche cells (ONCs), found at the interface of the bone and bone marrow where blood cells are formed, send aging signals to stem cells. So the researchers exposed stem cells in culture dishes to isolated old and young ONCs. The outcome, published January 28, 2010, in Nature, matched that of the first experiment: whereas old ONCs induced signs of age in young HSCs, old ONCs exposed to young blood regained their youthful characteristics.
While the scientists haven't yet pinpointed what ages the ONCs, and thereby the HSCs, Wagers suspects that more than one molecule is involved in regulation. She next plans to study the genes that are upregulated and downregulated in the blood and in ONCs as they age.