“I’m excited about being able to rejuvenate organs and tissues that fail due to aging and disease,” said senior author of the study David Sinclair, a professor of genetics at Harvard Medical School. “We hope to treat glaucoma in human patients (at the trial stage) in two years.”
This study published in Nature suggests a new approach to reversing age-related decline by reprogramming some cells to a more youthful state in which they are better able to repair or replace damaged tissues. However, the researchers note that thus far their work has only been carried out in mice and remains to be determined if this approach is translatable to humans, or to other tissues and organs that suffer the ravages of time.
This treatment is based on the properties that cells have when the body is developing as an embryo. The body is affected by aging in numerous ways such as adding, removing or altering chemical groups like methyls on DNA, and as a person ages, these epigenetic changes accumulate. As an embryo cells can repair and regenerate themselves, but this capacity declines with age rather rapidly. This has raised the possibility of epigenetic changes contributing to the effects of aging and questions such as if epigenetic changes are a driver of aging, can we reset the epigenome to reverse the clock?
In this study to investigate if they could turn back the clock to repair damage, the scientists modified a process usually used to create a blank state induced pluripotent stem cells by injecting a cocktail of 4 proteins that help to reprogramme a cell. Triggering these genes caused cells to lose their developmental identity and revert to a stem cell-like state. Rather than turning the genes on and leaving them as such the team turned them on for a few days then switched them off again with hopes of reverting the cells to a younger state without erasing their identity. This resulted in the mice aging more slowly, and they had a pattern of epigenetic markers indicative of younger animals. The disadvantage of this technique was that if the genes are present in extra copies or expressed for too long some of the mice developed tumors.
To look for a safer way to rejuvenate cells, the cocktail was tweaked to use just 3 of the youth-restoring proteins and was dubbed OSK. The scientists targeted the retinal ganglion cells in the eye which are linked to the brain through axons connections that form the optic nerve, damage to them caused by injury, aging or disease causes poor vision and blindness.
First, the team injected a virus into the eye to see if expression of the 3 genes would allow the animals to regenerate injured retinal nerves, which had yet to be done with any treatment. Results indicate that OSK was able to reverse damage caused by injury, the team turned focus to countering the effects of disease, specifically glaucoma which is the leading cause of blindness in humans. Conditions of disease were replicated where a build-up of pressure in the eye damages the optic nerve in several dozen mice, those receiving treatment with OSK experienced significant benefits.
The team was able to show that their approach improved the visual acuity in mice with age-related vision loss or animals with increased pressure inside the eye which is a hallmark of glaucoma. According to the team, their approach also reset epigenetic patterns to a more youthful state in mice and human cells grown in the lab.
According to Judith Campisi, who is a cell biologist at the Buck Institute for Research on Aging more data should be emerging rather quickly, as she explains,” There are many labs now who are working on this whole concept of reprogramming. We should be hopeful but, like everything else, it needs to be repeated and it needs to be extended.”
