A protein in blood can repair age-related damage in the brains and muscles of old mice, returning them to a more youthful state.
Last year, the protein, called growth differentiation factor 11 (GDF11), was found to have a restorative effect on mouse hearts. If it does a similar job in humans, it could have huge potential for treating a wide-range of age-related diseases, say the researchers behind the latest work.
The idea that an infusion of young blood could regenerate ageing bodies was explored several years ago when the circulatory systems of old mice were physically connected to those of young animals, as if they were conjoined twins. This rejuvenated the stem cells in the bone marrow of the older mice that replenish their blood, and led to a wave of studies comparing the blood of old and young mice to try and identify the youth-giving substance.
The latest results include two studies from Amy Wagers’s lab at Harvard University. One explored the potential of GDF11 in muscle regeneration and the other in brain regeneration.
In the brain study, the researchers injected 15-month-old mice – which is just over half their natural life span – with GDF11 daily for a month. The volume of the blood vessels in their brain increased by 50 per cent and the number of brain stem cells by 29 per cent. Both factors are known to improve brain function.
Muscle fibres in old mice injected with GDF11 doubled in size to match that of 2-month old mice. Images from an electron microscope show a striking reordering of muscle fibres from a disordered state to the highly regular appearance of young muscle.
The endurance of the mice also improved, enabling them to spend an average of 57 minutes on a treadmill compared with 35 minutes for untreated old mice.
Next stop humans?
Wagers says GDF11 has huge potential to rejuvenate heart, brain and muscle tissue. However, she wants to find out more about GDF11 before trying it in patients. “I believe there’s still some very important pre-clinical work we need to do, including understanding why GDF11 is lost with age, and whether there is counter-regulation of it that may develop in older mice,” she says.
“I think we can answer those questions in the next three to five years and be ready for a trial within that timeframe,” she says.
In a separate study, a team led by Tony Wyss-Coray at the Stanford School of Medicine in California gave 18-month-old mice, the equivalent of mid-to-late middle age, eight injections of blood plasma taken from 3-month-old mice. Three weeks later, the brain cells of the older mice had 20 per cent more dendrites, the spines that relay messages between neurons, than mice given a placebo.
The mice performed about 50 per cent better on two standard tests of cognitive function. “We’re extremely excited about the clinical possibilities,” says Wyss-Coray. “The studies show the old brain is plastic and can recover function, and that this can be done so simply, just by injecting ‘young’ blood plasma,” he says.
His team is already planning a human trial. They want to inject blood plasma from young, healthy donors into people with Alzheimer’s disease to see if it improves their brain function. “We hope to start this year,” he says.
Stanford paper – Nature Medicine, DOI: 10.1038/nm.3569
Harvard papers – Science, DOI: 10.1126/science.1251141; Science, DOI: 10.1126/science.1251152
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