Antibody can protect brains from the ageing effects of old blood

Old blood may have a powerful effect in terms of damaging organs and contributing to ageing, but a compound has been developed that seems to protect against this, preventing mice’s brains from ageing (New Scientist, 2017).

The effects of blood on ageing were first discovered in experiments that stitched young and old mice together so that they shared circulating blood. Older mice seem to benefit from such an arrangement, developing healthier organs and becoming protected from age-related disease. But young mice aged prematurely.

These experiments suggest that, while young blood can be restorative, there is something in old blood that is actively harmful. Now Hanadie Yousef at Stanford University seems to have identified a protein that is causing some of the damage, and has developed a way to block it. She has found that the amount of a protein called VCAM1 in the blood increases with age. In people over the age of sixty five, the levels of this protein are 30% higher those under twenty five.

To test the effect of VCAM1, Hanadie Yousef injected young mice with blood plasma taken from older mice. Sure enough, they showed signs of ageing; more inflammation in the brain, and fewer new brain cells being generated, which happens in a process called neurogenesis.

Blood plasma from old people had the same effect on mice. When Hanadie Yousef injected plasma from people in their late sixties into the bodies of three month old mice, about twenty years old in human terms, the mice’s brains showed signs of ageing. These effects were prevented when she injected a compound that blocks VCAM1. When the mice were given this antibody before or at the same time as old blood, they were protected from its harmful effects.

“When we age, we all have decreased cognitive function, decreased neurogenesis, and more inflammation in the brain,” said Hanadie Yousef, who presented her findings at the Society for Neuroscience annual meeting in San Diego in November last year. She said “If we can figure out the mechanisms and reverse that, then we could promote healthy ageing. That’s what I truly believe will come out of this research eventually.”

Jonathan Godbout at Ohio State University said “It’s a sound study and it has a lot of potential.” He said he’d like to see more data, but is cautiously optimistic that the work could lead to a treatment that could protect ageing brains.

Some teams have begun giving plasma from young donors to older people, to see if it can improve their health, or even reduce the effect of Alzheimer’s disease. Hanadie Yousef said for the best chances of success, the damaging effects of old blood will need to be neutralised.

Miles Herkenham at the National Institute of Mental Health in Bethesda, Maryland, said he is impressed with Hanadie Yousef’s findings. He said it was very surprising that a single protein seems to have such a huge effect, but the results need to be replicated by another lab. He said “I like the idea, but I wouldn’t want to rush into human trials yet.”

Hanadie Yousef said a drug that protects people from the effects of old blood would be preferable to plasma injections. If transfusions from young donors turn out to be effective, it would be difficult to scale this up as a treatment for everyone. Drugs that block harmful proteins in the blood would be cheaper, safer and more accessible. Hanadie Yousef said “At the end of the day, nobody wants blood transfusions. We want rejuvenating proteins and antibodies to help people age in a healthy manner.” She is patenting her compound, and hopes to develop a treatment to protect people from the effects of ageing.

The fact that Hanadie Yousef’s antibody protects the mouse brain is particularly promising, because most drugs aren’t able to get into the brain, they fail to pass through the protective cell barrier that separates the brain from the body’s bloodstream. Her drug doesn’t need to pass this barrier, because the protein it targets is present in the cells of the barrier itself.

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