The regenerative power of young blood appears to be mediated by osteoblasts--bone-forming stem cells previously shown to play a role in regulating blood-forming stem cells. Researchers found that osteoblasts from old animals can make blood-forming stem cells from young mice act old. And conversely, surgically exposing old mice to young blood rejuvenates aged osteoblasts, restoring their capacity to properly regulate blood-forming stem cells.

Researchers haven't yet identified the mysterious molecule in blood that controls these aging effects. But insulin-like growth factor 1 (IGF-1), a hormone that has been shown to regulate longevity in a number of organisms, may play a key role. Researchers found that they could partially correct aging defects in osteoblasts by suppressing IGF-1. On the other hand, suppressing IGF-1 in muscle cells has the opposite effect, highlighting the complex role this molecule probably plays in aging.

It remains to be seen just what effect rejuvenating the circulatory system will have on the animals long-term. For example, scientists haven't assessed whether older mice surgically exposed to young blood are more resistant to infection than their normal aged counterparts. "But there are lots of reasons to link changes in [the circulatory system] with changes in the immune system," said Wagers. Older mice produce fewer lymphocytes, which respond to viruses and other pathogens. And they produce more myeloid cells, which tend to promote inflammatory conditions. "In a lot of tissues, you see an increase in inflammation that occurs with age," said Wagers.

The research also has important implications for regenerative medicine, such as stem cell transplants. "Most effort has focused on how to make [replacement] cells," says Linheng Li, a researcher at the Stowers Institute for Medical Research, in Kansas City, MO, who was not involved the study. "But we need to focus on making cells that function properly." Blood-forming stem cells, for example, are made in great quantities with age. But those cells don't work as well as younger ones. "It highlights the importance of the environment into which you transplant them," said Wagers. "If you take young healthy cells, and put them into an old environment, you might not get the full regenerative benefit of the cells."