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.