Young blood really is the key to youth

HUMANS are constantly searching for an elixir of youth - could it be that an infusion of young blood holds the key?

This seems to be true for mice, at least. According to research presented this week at the Society for Neuroscience conference in New Orleans, Louisiana, giving young blood to old mice can reverse some of the effects of age-related cognitive decline.

Last year, Saul Villeda, then at Stanford University in California, and colleagues showed they could boost the growth of new cells in the brains of old mice by giving them a blood infusion from young mice (Nature, doi.org/c9jwvm).

"We know that blood has this huge effect on brain cells, but we didn't know if its effects extended beyond cell regeneration," he says.

Now the team has tested for changes in cognition by linking the circulatory systems of young and old mice. Once the blood of each conjoined mouse had fully mixed with the other, the researchers analysed their brains.

Tissue from the hippocampus of old mice given young blood showed changes in the expression of 200 to 300 genes, particularly in those involved in synaptic plasticity, which underpins learning and memory. They also found changes in some proteins involved in nerve growth.

The infusion of young blood also boosted the number and strength of neuronal connections in an area of the brain where new cells do not grow. This didn't happen when old mice received old blood.

To find out whether these changes improved cognition, the team gave 12 old mice eight intravenous shots of blood plasma either from a young or an old mouse, over the course of one month. They used plasma rather than whole blood to exclude any effect produced by blood cells.

The mice then took part in a standard memory task to locate a hidden platform in water. The old mice that had received young blood plasma remembered where to find the platform much quicker than the mice on the old plasma.

To find out which brain area was involved in this reversal of cognitive decline, the team performed fear conditioning tests. Mice that had been given young blood were better at remembering fear associated with tasks that activated the hippocampus, suggesting that young blood has a specific effect on this area of the brain.

But the mystery remains: what exactly is it about young blood that old blood doesn't have? "We have not identified any individual factors responsible for the rejuvenating effects of young plasma yet," says Tony Wyss-Coray, also at Stanford. His team is now trying to identify possible candidates such as lipids and hormones.

Villeda is hopeful the results might one day translate to humans since the components of blood that change with age in mice mirror those in humans.

While "it's plausible that similar mechanisms operate in humans," says Joseph Quinn at Oregon Health and Science University in Portland, there is no evidence yet to support this.

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