Scientists have been rejuvenating old mice with infusions of not just the blood of younger mice, but even blood from teenage human beings – and we finally have our first clues on why this strange technique works.
Researchers have discovered an enzyme that helps rescue ageing brains from cognitive decline. So far it’s only been shown in mice, but if the same mechanisms are found in humans, it could lead to a new class of anti-ageing therapies.
Four years ago, a team of researchers led by neurobiologist Saul Villeda from the University of California, San Francisco, discovered that giving older mice infusions of blood from younger mice improved their memory and learning by improving connections in the hippocampus.
By the same token, they also found that giving the younger mice ‘old blood’ led to an increase in cognitive aging.
Ever since, Villeda’s lab has been searching for the secret to this slightly vampiric fountain of youth – and now they think they have it.
The team used a technique called parabiosis, which involved surgically connecting the circulatory systems of a pair of mice of two different relative ages; either a spry 3, mature 6, or seasoned 18 months.
Then the researchers analysed the mouse brains to measure the levels of an enzyme thought to be involved in some age-related diseases.
“At first I didn’t believe it,” says the study’s lead author Geraldine Gontier from UCSF.
“I did the experiment again and again to make sure that it was right. But it became clear that some circulating factor in the blood is able to change the level of Tet2 in the brain.”
Tet2 – or ten eleven translocation methylcytosine dioxygenase 2 – is known to play a role in epigenetically regulating activity in a number of genes. As we age, mutations in the gene for this enzyme accumulate, leading to an increased risk of cancer, stroke, and cardiovascular disease.
Some of the genes it ‘tags’ are understood to be responsible for regenerating brain cells. The fact it becomes less efficient as we age potentially goes a long way to explaining our cognitive decline in our twilight years.
Finding elevated levels of Tet2 active in the hippocampi of older mice was a red flag that warranted further investigation, so the researchers did a second experiment using short sequences of RNA to block the Tet2 activity in 3-month-old juvenile mice.
Sure enough, all of the the younger mice had a reduced number of brand new neurons in their hippocampus as a result. They also performed worse on learning and memory tests.
In one last experiment, the team designed viruses that forced hippocampus cells to pump out Tet2 in adult mice, all aged around 6 months.
Once again the higher enzyme levels were found to increase epigenetic tagging and were implemented in the production of fresh new brain cells.
While the rejuvenation didn’t necessarily help them in all of their memory tests, there were moderate improvements.
“This was amazing because it’s like improving memory in a healthy, 30-year-old human,” says Villeda.
It’s not like 30-year-old humans are ready for retirement, so any kind of improvement comes as a surprise, especially given it all comes down to a single enzyme.
“I’ve spent my entire PhD and now my postdoc trying to understand how the brain ages and how can we reverse it,” says Gontier.
“And in this study, we find that one molecule, Tet2, is able to rescue regenerative decline and enhance some cognitive functions in the adult mouse brain.”
As exciting as the idea is, we have to remember that so far it’s only been demonstrated in mice. There’s good reason to suspect these processes occur in humans, but further studies are required.
Coming up with a simple way to hold back cognitive decline would be a boost for adding years of quality to our lives, so research like this is worth watching.
Especially if it means avoiding transfusions of teenage blood.
This research was published in Cell Reports.
