Rejuvenating Tet2

The mechanism of brain rejuvenation with the blood of young animals has been found

Sergey Vasiliev, Naked Science

It is known that blood transfusion of young mice can slow down the development of many signs of aging in their older relatives. It is possible to "rejuvenate" laboratory animals even by injecting the blood of human adolescents. This effect is associated with the work of regulatory proteins that have not yet been precisely identified. One of the candidates for this list is the GDF11 protein (growth differentiation factor 11), whose content in the blood of mice decreases with age, although many scientists tend to question its role. Another promising candidate is put forward by a new paper published by the journal Cell Reports (Gontier et al., Tet2 Rescues Age-Related Regenerative Decline and Enhances Cognitive Function in the Adult Mouse Brain).

A few years ago, Saul Villeda from the University of California, San Francisco, and his colleagues showed that transfusion of young blood to old mice improves their memory and learning ability. It worked the other way around: injections of "old" blood to young animals stimulated the "aging" of their brains. To find the cause of these changes, the authors surgically connected the circulatory systems of different ages – cubs 3 months from birth, young 6- and mature 18-month-olds, finding that certain factors contained in the "young" blood stimulate the activity of the TET2 gene in brain cells.

Its product, the protein Tet2 (Tet-methylcytosine dioxygenase 2), participates in the epigenetic regulation of many genes, but with age its own activity decreases – among these genes there are those that are responsible for the renewal of brain cells. Noting an increase in the level of Tet2 in the hippocampus of old mice, the scientists set up the following experiment by blocking the activity of this protein in three-month-old mice using specially synthesized short-chain RNA molecules. As might be expected, such animals subsequently showed a reduced number of neurons in the hippocampus, and they performed worse in tests for cognitive abilities.

Finally, scientists have obtained artificial viral particles that are harmless, but capable of penetrating into hippocampal cells and increasing Tet2 synthesis in adult mice. Such viruses were introduced into the organisms of six-month-old mice, which increased the regulatory activity of their genome and stimulated the development of neurons. The increase in cognitive functions was not as noticeable as their degradation in the previous experience, but the tests still showed moderate improvements. However, this result can also be considered amazing. "It's as if we have improved the memory of a healthy 30-year–old," says Wileda in a UCSF Cognitive Benefits of 'Young Blood' press release Linked to Brain Protein in Mice.

"I spent years... trying to understand how the brain ages and how to reverse this process," the scientist continues. "And in this work, we found that a single molecule, Tet2, is able to stop the decline in regenerative functions and to some extent improve the cognitive functions of the brain of adult mice."

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