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Young Blood Reverses Signs of Aging in Old Mice

A mysterious substance in blood rejuvenates blood-forming stem cells.
January 27, 2010

The antiaging power of blood might not be just the stuff of vampire stories. According to new research from Harvard University, an unspecified factor in the blood of young mice can reverse signs of aging in the circulatory system of older ones. It’s not yet clear how these changes affect the animals’ overall health or longevity. But the research provides hope that some aspects of aging, such as the age-related decline in the ability to fight infection, might be avoidable.

Blood rebirth: Over time, blood stem cells (shown in green) lose their ability to replenish blood. Researchers have discovered that exposing old mice to circulating blood from younger mice restores this ability.

“At least some age-related defects are reversible, and the factors to reverse them are carried in blood,” said Amy Wagers, a researcher at the Harvard Stem Cell Institute and Joslin Diabetes Center, in Boston, at a press conference on Tuesday. Identifying those factors could lead to new strategies to boost resistance to infection, and perhaps a decrease in some cancers, she said.

In the experiment, Wagers and team surgically connected the circulatory systems of two mice, allowing older animals to be exposed to blood–and all the molecules and cells it carries– from young animals. They found that the procedure made the blood-forming stem cells in older animals act young again; the overall number of these cells decreased, and the cells generated different varieties of blood cells in more appropriate ratios. “In aged animals, many of the changes we see normally that are associated with age were reversed,” said Wagers.

The findings, published today in the journal Nature, and which follow similar results with muscle stem cells, also suggest that the regenerative capacity of stem cells is highly influenced by their environment, which could have both positive and negative implications for regenerative medicine.

As we age, our body loses its ability to regenerate different tissues. The circulatory system reflects this decline clearly–the number of blood-forming stem cells, which reside in bone marrow and generate all types of blood cells, increases. But these cells paradoxically lose their ability to repopulate the blood and generate cells in inappropriate ratios, creating too few immune cells, called B lymphocytes, and too many inflammatory cells.

One theory for aging is that our stem cells eventually wear out, thanks to intrinsic changes within the cells. While previous research supports this idea, findings from Wagers and others show that the age-related decline in stem cells is also influenced by external forces. For example, exposing skeletal muscle to blood-borne factors from young mice can restore the regenerative capacity of muscle stem cells.

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.”

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