Mice regain sight thanks to “anti-aging” genes

Aging is inevitable ? This process, which affects all cells, first induces dysfunctions before causing cell death. The level of genome, aging would be palpable. The scientific community believes it is due to the accumulation of epigenetic changes that alter the normal functioning of Genoa.

Harvard University School of Medicine scientists came up with an attractive but still controversial idea: reversing the signs of aging accumulated in the genome in cancel aging. I study them publish in Nature, December 2, 2020, does not formally prove this theory, but offers a number of experiments that support it.

Thanks to a cocktail of three genes, they managed to limit the degeneration of neurons and promote their regeneration. Mice with glaucoma then recovered them visual acuity.

Three anti-aging genes

The three geniuses chosen, Oct4, Sox2 is Klf4 (also noted OSK) by scientists have been used for ten years in cellular dedifferentiation experiments. This involves the transformation of a differentiated adult cell into a pluripotent stem cells, a state that can be described as juvenile. Pluripotent stem cells are capable of differentiating into several distinct cell types.

But the principle chosen by Harvard University scientists is not to rejuvenate cells by playing on their identity or differentiation, but rather by modifying their epigenetic markers, and more specifically methyl groups.

The first experiment concerns the effect of the trio of “reprogrammed genes” on the regeneration of neurons. For this, the scientists were interested in the retinal ganglion cells, which are part of the nerf optics behind theeye. With forceps, they damaged the optic nerve in adult mice, then injected the OSK genes (the three genes in one virus adenoassociate). This treatment allowed to limit the cell death of damaged neurons, but also to stimulate the growth of new ones.

In embryonic form and after birth, neurons are able to regenerate in mice, but this ability disappears over time. Here the injection of the OSK genes therefore had an “anti-aging” effect, restoring a capacity of the neurons present only in young animals.

But that is not all. Four days after the forceps wound, the process of methylation accelerated in retinal ganglion cells. The methylation patterns therefore correspond to those of a cell at the end of its life. With their activity, the OSK genes simply reversed them all over theADN, but more specifically around the genes involved in the detection of light and synaptic transmission. Neurons have found a second youth.

Mice that cover their sight

The following experiment concerns a disease eye which appears with age: glaucoma. Glaucoma is associated with the gradual increase in pressure intraocular which damages the optic nerve and leads to progressive loss of vision. To mimic this disease in mice, the scientists artificially increased eye pressure by injecting spheres into the anterior chamber of the eye. After 21 days, the OSK genes were injected. The treated eye therefore has a density ofaxons more functional than the untreated diseased eye. The mice also underwent an eye test; those treated recovered their sight, not all of them, but up to 50% of what they had lost.

In a final experiment, the scientists injected the reprogramming genes into the eyes of one-year-old mice. At this age their vision has already decreased compared to that of the younger ones. It’s about 15% lower than five-month-old mice. After four weeks of treatment, older mice can see just as well as younger ones. Their epigenetic modification then it has the same profile.

These three experiments show that cells respond to OSK genes by readjusting the epigenetic changes they bring, matching them to those seen in younger subjects. The success of the injections also depends on the presence and activity of demethylases (TET1 and TET2), enzymes which remove methyl groups from DNA. In the mice with less, the results were less impressive.

Wanting at all costs to rejuvenate our cells, he seems to be trying to escape the ravages of time and the diseases it causes. But modulating cells in this way is not without risk, cell rejuvenation can lead to the appearance of cancer. All the mechanisms involved are not yet understood and experiments need to be replicated before considering this approach as a possible treatment against the effects of aging, especially in degenerative eye diseases.