‘Young blood’ anti-ageing mechanism questioned

The hunt for the fountain of youth is back to square one- at least for those seeking it in blood.

New findings cast doubt on research that attempted to explain why the muscles of an old animal could be rejuvenated with a dose of blood from a young animal.

For decades, scientists have sought to understand the anti-ageing effects of parabiosis, a technique in which researchers sew a young mouse and an old mouse together so that they share a circulatory system.

The young mouse’s blood seems to rejuvenate the old mouse, regenerating its wasting muscles and restoring its cognitive abilities.

On the basis of those results, at least one company is attempting to replicate the effect in humans using blood plasma from healthy young people to treat patients with Alzheimer’s disease.

In 2013, a team led by Amy Wagers, a stem-cell researcher at Harvard University in Cambridge, Massachusetts, seemed to offer an explanation for this blood-doping effect.

The scientists found that levels of a protein called GDF11 decreased in the blood of mice as they grew older.

When the researchers injected the protein into the heart muscle of old mice, it became ‘younger’- thinner and better able to pump blood.

Two subsequent studies by Wagers and her colleagues found that GDF11 boosted the growth of new blood vessels and neurons in the brain and spurred stem cells to regenerate skeletal muscle at the sites of injuries.

Those results quickly made GDF11 the leading explanation for the rejuvenating effects of transfusing young blood into old animals. But that idea was confusing to many because GDF11 is very similar to the protein myostatin, which prevents muscle stem cells from differentiating into mature muscle- the opposite effect to that seen by Wagers and her team.

For GDF11, “You could imagine that when it came out last year that it helped muscle, it was quite a surprise,” says David Glass, executive director of the muscle diseases group at the Novartis Institutes for Biomedical Research in Cambridge, Massachusetts. “Did we miss something?”

Glass and his colleagues set out to determine why GDF11 had this apparent effect. First, they tested the reagents that Wagers’ group had used to measure GDF11 levels, and found that these chemicals could not distinguish between myostatin and GDF11.

When the Novartis team used a more specific reagent to measure GDF11 levels in the blood of both rats and humans, they found that GDF11 levels actually increased with age — just as levels of myostatin do. That contradicts what Wagers’ group had found.

Glass’s team next used a combination of chemicals to injure a mouse’s skeletal muscles, and then regularly injected the animal with three times as much GDF11 as Wagers and her team had used.

Rather than regenerating the muscle, Glass found, GDF11 seemed to make the damage worse by inhibiting the muscles’ ability to repair themselves. He and his colleagues report their results on 19 May in Cell Metabolism.