Antibody can protect brains from the ageing effects of old blood
Old blood may have a powerful effect, damaging organs and contributing to ageing. Now a compound has been developed that seems to protect against this, preventing mice’s brains from ageing.
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.
Such 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 in California seems to have identified a protein that is causing some of the damage, and has developed a way to block it.
Yousef has found that the amount of a protein called VCAM1 in the blood increases with age. In people over the age of 65, the levels of this protein are 30 per cent higher than in under-25s.
To test the effect of VCAM1, 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 she injected plasma from people in their late 60s into the bodies of 3-month-old mice – about 20 years in human terms – the mice’s brains showed signs of ageing.
These effects were prevented when Yousef 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,” says Yousef, who presented her findings at the Society for Neuroscience annual meeting in San Diego in November last year. “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.”
“It’s a sound study and it has a lot of potential,” says Jonathan Godbout at Ohio State University in Columbus. He says 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. But for the best chances of success, we’ll also need to neutralise the damaging effects of old blood, says Yousef.
Miles Herkenham at the National Institute of Mental Health in Bethesda, Maryland, says he is impressed with Yousef’s findings. It’s very surprising that a single protein seems to have such a huge effect, he says, but the results need to be replicated by another lab. “I like the idea, but I wouldn’t want to rush into human trials yet,” he says.
Target the old
A drug that protects people from the effects of old blood would be preferable to plasma injections, says Yousef. Should transfusions from young donors turn out to be effective, it would be difficult to scale this up as a treatment for all. Drugs that block harmful proteins in our own blood would be cheaper, safer and more accessible.
“At the end of the day, nobody wants blood transfusions,” says Yousef. “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 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.
Yousef’s drug doesn’t need to pass this barrier, because the protein it targets is present in the cells of the barrier itself.
And the alternative story…
Blood from human teens rejuvenates body and brains of old mice
Blood plasma from young people has been found to rejuvenate old mice, improving their memory, cognition, and physical activity. The method has the potential to be developed into a treatment for people, says Sakura Minami of Alkahest, the company behind the work.
Previous research has found that stitching old and young mice together has an interesting effect. While sharing a blood system works out well for the older mouse, the younger one isn’t so lucky. The young animals started to show signs of brain ageing, while the brains of the older mice started to look younger. “We see a rejuvenation effect,” says Minami.
The key to youth appears to be in the blood plasma – the liquid part of blood. Several studies have found that injecting plasma from young mice into old mice can help rejuvenate the brain and other organs, including the liver, heart, and muscle.
Could blood plasma from young people have the same benefits? To find out, Minami and her colleagues took blood samples from 18-year-olds, and injected them into 12-month-old mice. At this age, the equivalent of around age 50 for people, the mice start to show signs of ageing – they move more slowly, and perform badly on memory tests.
The mice were given twice-weekly injections of the human plasma. After three weeks of injections, they were submitted to a range of tests. The treated mice’s performance was compared to young, 3-month-old mice, as well as old mice who had not received injections.
They found that human plasma does have the power to rejuvenate. Treated mice ran around an open space like young mice. Their memories also seemed to improve, and they were much better at remembering their way around a maze than untreated mice.
“Young human plasma improves cognition,” says Minami, who presented her findings at the Society for Neuroscience annual meeting in San Diego, California, on Monday. “Their memory was preserved.”
“It’s more or less what we would expect,” says Victoria Bolotina, at Boston University in Massachusetts. “The blood of young people must have something in it that’s important for keeping them young,” she says.
The team then examined the brains of the treated and untreated mice. They looked for clues on the birth of new neurons in the hippocampus – a process called neurogenesis, which is thought to be important for memory and learning. Sure enough, the treated mice appeared to have created more new cells in their brain. “Young human plasma treatment can increase neurogenesis,” says Minami.
Minami says she has identified some factors in young blood that might be responsible for these benefits, but that she won’t reveal what they are yet. Some of them seem to be crossing into the brain, while others may be acting remotely, elsewhere in the body, she says.
She hopes to one day translate the findings into an anti-ageing treatment for people – one that might help those who start to experience the effects of an ageing brain. “There’s anecdotal evidence that people experience benefits after blood transfusions,” she says.
The company she works for, Alkahest, has already started a trial of young blood in people with Alzheimer’s disease.