Blind Mice with Glaucoma See Again Through Simple Technique that Promotes Youthful Gene Expression

Blind Mice with Glaucoma See Again Through Simple Technique that Promotes Youthful Gene Expression

Researchers at Harvard Medical School have successfully restored vision loss and reversed glaucoma-induced damage in mice.

In the mice, the retinal ganglion cells, a principal cell that enables vision, were restored to a youthful state in cases of glaucoma, as well as when the optic nerve, another key component of eyesight, had been damaged. Both were achieved through expressing certain transcription factors—proteins that turn genes on and off.

“The study sheds light on the mechanisms of ageing, and identifies new potential therapeutic targets for age-related neuronal diseases such as glaucoma,” reads a statement from researchers at Harvard Medical School.

The new study, published in Nature, was conducted by Dr. David Sinclair, of the world’s foremost experts on ageing-related research in mice.

Along with genetic research, Sinclair has also looked at how supplement-ready compounds like resveratrol and Metformin affect aging, and his book, Lifespan: Why We Age and Why We Don’t Have To, is a New York Times bestseller.

Repairing a scratched CD
The science behind Sinclair’s new paper involves the curious process of methylation. Governed by epigenetics—that is, changes in the genetic expression of the cell over time—the researchers found that methylation in mammalian tissues prevents the cells from replicating proteins properly while simultaneously encoding a kind of genetic history.

One can imagine this as scratches on the bottom of a CD. If the scratches could be removed, the record of proper function is still there, and could still be read by the laser in a CD player.

In his book, Sinclair details the modern theory of aging, which is that changes in epigenetics and damage to cells and tissues prevent the body from properly reading protein-encoding genes, resulting in either faulty, less-functional, i.e. older genes being transcribed, or the proteins not being replaced at all.

Here the authors found that when the mouse neurons were recovering from damage related to glaucoma, the methyl groups which built up over time left, like the scratches being removed from a disk.

This resulted in a process called demethylation. Demethylation was associated with younger genetic expression, in other words, the mouse’s genes remembered how to be young again, only after demethylation had occurred.

“These data indicate that mammalian tissues retain a record of youthful epigenetic information—encoded in part by DNA methylation—that can be accessed to improve tissue function and promote regeneration in vivo,” write the authors in their summary.

It remains to be seen whether records of youthful genetic expression are contained within other mammalian tissues, the liver for a random example, through methylation, and whether or not they can be accessed through demethylation.

If it’s true that simply altering some transcription factors is enough to clear the dust off the rule book for how to build young proteins, Sinclair stands to make a major breakthrough.