BLOOD from the young seems to have healing powers, but how can we harness them without relying on donors? The discovery of a protein that keeps blood stem cells youthful might help.
The rejuvenating properties of young blood came to light in macabre experiments that stitched young and old mice together to share a circulatory system. The health of the older mice improved, while that of the younger ones deteriorated. Other animal studies have since shown that injections of young or old blood have similar effects.
This may work in people too. Young blood is being trialled as a treatment for conditions like Alzheimer’s, and aged mice that received injections of blood from human teenagers showed improved cognition, memory and physical activity levels.
But these studies rely on young people donating their blood: if this became the go-to therapy for age-related disease it would be difficult to get enough donations to fulfil demand.
“We think the drug will improve signs of ageing and boost the immune systems of older people”
The stem cells in our blood could provide an alternative approach. Our red and white blood cells are made by stem cells that themselves come from “mother” stem cells in bone marrow. But as we age, the number of these mother stem cells declines. One of the world’s longest-lived women seemed to only have two left in her blood when she died at age 115.
The decline in mother stem cells causes people to have fewer red blood cells, and white blood cells called B and T lymphocytes. These declines can cause anaemia and weaken the immune system. “Usually the immune system in the elderly is not prepared to fight infections very hard,” says Hartmut Geiger at the University of Ulm in Germany.
When Geiger’s team examined the bone marrow in mice, they found that older animals have much lower levels of a protein called osteopontin. To see if this protein has an effect on blood stem cells, the team injected stem cells into mice that lacked osteopontin and found that the cells rapidly aged.
But when older stem cells were mixed in a dish with osteopontin and a protein that activates it, they began to produce white blood cells just as young stem cells do. This suggests osteopontin makes stem cells behave more youthfully (EMBO Journal, doi. org/b4jp). “If we can translate this into a treatment, we can make old blood young again,” Geiger says.
“It’s exciting,” says Hanadie Yousef at Stanford University in California. But longer term studies are needed to see whether this approach can rejuvenate the whole blood system, she says. Until now, most efforts to use blood as a rejuvenation agent have focused on plasma, the liquid component, as some believe it carries dissolved factors. that help maintain youth. But Geiger thinks the cells in blood might play a key role, because they are better able to move into the body’s tissues.
Both soluble factors and blood cells are likely to be important, says Yousef. While injections of young plasma rejuvenate older animals, the treatment doesn’t have as strong an effect as when young and old animals share a circulatory system, she says.
Geiger’s team is developing a drug containing osteopontin and the activating protein to encourage blood stem cells to behave more youthfully. “It should boost the immune system of elderly people,” he says.
Such a drug might have benefits beyond fighting infection and alleviating anaemia. The team also think the protein will boost levels of mother stem cells. Having only a small number of such cells has been linked to heart disease, so Geiger says there is a chance that boosting them may help prevent this.
Osteopontin might also be useful for treating age-linked blood disorders, such as myelodysplasias that involve dysfunctional cells, says Martin Pera of the Jackson Laboratory in Bar Harbor, Maine. “It is possible that rejuvenating bone marrow stem cells could help with these conditions,” he says.
“This study provides more evidence that cells can be rejuvenated,” says Ioakim Spyridopoulos at Newcastle University, UK. “They have made old blood look young again, although whether it acts young or not will have to be shown in clinical trials.”