Biotechnology: this company claims to have extended the life of mice by reprogramming their cells

A small biotech company, Rejuvenate Bio, claims to have used a technology called “cellular reprogramming” to rejuvenate old mice and extend their lives. A result that suggests that one day, the elderly could see their biological clock be delayed thanks to an injection. Thus, they would literally become younger.

This rodent life extension claim made by Rejuvenate Bio was cited in a preliminary article published on the BioRxiv website and has not been peer reviewed.

The cell reprogramming technique of returning cells to a more youthful state has been the subject of investments amounting to hundreds of millions of dollars. Scientists had already shown it worked on single cells in the lab and are now trying to determine if the rejuvenating effect also works in living animals.

The Rejuvenate Bio article is widely awaited proof that this method can actually prolong the lives of animals.

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Noah Davidsohn, Chief Scientific Officer at Rejuvenate Bio, reveals that the company used gene therapy to add three powerful reprogramming genes into the bodies of mice whose age matched that of a 77-year-old human.

After treatment, their remaining lifespan doubled, says the San Diego-based company. Treated mice lived 18 weeks longer, on average, while control mice died in nine weeks. Overall, the treated mice lived about 7% longer.

While the increase in lifespan is modest, the company says this research demonstrates the reversal of aging in an animal. “It’s a powerful technology and here is the materialization of the concept”, enthuses Noah Davidsohn. “I wanted to show that it is really something which can be applied to our elderly population”.

Scientists unrelated to the company called the study an exciting milestone but warned that whole-body rejuvenation through gene therapy remains a misunderstood concept with huge risks. “It’s a nice intellectual exercise but I would be careful not to do anything like a human,” says Vittorio Sebastiano, a professor at Stanford University.

One of the risks involved is that the powerful programming process may cause cancer. Such an effect is often observed in mice.

Despite this, the possibility that rescheduling is an elixir of youth has led to a boom in research and investment. One company, Altos Labs, claims to have raised more than three billion dollars.

In the lab, reprogramming works by exposing individual cells to a set of three or four proteins that are typically active in early-stage embryos. Several days after the treatment has been inoculated, even old cells turn into young stem cells.

In 2012, the Nobel Prize in Medicine awarded to a biologist for his work on the reprogramming of adult cells

The discovery of the recipe leading to the reprogramming won Japanese biologist Shinya Yamanaka a Nobel Prize in 2012.

Four years later, scientists from the Salk Institute tried the technique on live mice suffering from premature aging, similar to a human disease called progeria. They exposed whole mice to the factors for brief periods and found that some survived longer.

The next step, necessary for reprogramming to be considered a true intervention against aging, was to show that it could also extend the lives of healthy mice.

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“Everyone in the research community knows that the experiment that makes the difference is when you treat normal mice and see if you get a longer lifespan or better overall health,” says Martin Borch Jensen, creator of Impetus Grants, an organization that funds research on aging.

When several years passed without obtaining such a result, doubts began to grow about the effectiveness of the method. The hope that scientists could create mice with exceptional longevity began to fade. “Different teams have tried this experiment and the results have not been positive so far,” said Alejandro Ocampo, a biologist at the University of Lausanne, Switzerland, who carried out Salk’s original experiments.

However, last year a first report was published by a team working with mice genetically modified from birth to produce the special Yamanaka factors in their bodies. This team, which works at the National Institute of Health and Medical Research, found a trend towards longer lifespans, but this report was considered preliminary.

In the case of the work carried out by Rejuvenate Bio, the treatment was administered using gene therapy – viruses specially designed to transfer genes into cells. According to Noah Davidsohn, this makes the treatment similar to actual medical treatments people might receive.

Mice only live a few months in the wild but can survive two or three years in the laboratory. Those who took part in the last experiment were already 124 weeks old when they received the drug, that is to say, they were almost at the end of their life. According to Noah Davidsohn, the treated mice not only survived significantly longer, but they also performed better in terms of general health.

The magnitude of observed life extension is not in itself unprecedented. A US government program that tests drugs for their effects on longevity has shown that several compounds, including rapamycin, can extend the life of mice by 5 to 15%.

However, mice must take these drugs for a large part of their life, whereas the reprogramming has immediate effects. “It’s as if you could do nothing for your whole life and still get the benefits,” insists Noah Davidsohn.

The next step: extending the lifespan of human beings?

Rejuvenate Bio is currently developing gene therapy drugs for pet dogs and humans, including one to treat heart failure. Noah Davidsohn affirms that in the long term, he is convinced that it will be possible to rejuvenate human beings. “I wouldn’t work on this project if I didn’t believe in it,” he insists.

Much more information will be needed to learn exactly what changes reprogramming genes cause in mice, and the researchers say other groups will have to repeat the experiment before they are convinced. “I would like another team to do similar work and dig deeper into what is really going on,” says Borch Jensen.

According to Vittorio Sebastiano, the life-prolonging effect reported by Rejuvenate Bio could be due to changes at the level of a single organ or a single group of cells rather than a general rejuvenation effect on the scale. of the mouse. Among other shortcomings of its research, Rejuvenate Bio failed to carefully document which cells and how many were changed by the gene treatment.

Several companies are now pursuing their reprogramming projects but they choose recognized pathologies and concentrate their efforts on specific organs.

Turn Bio, a company co-founded by Vittorio Sebastiano, hopes, for example, to inject reprogramming factors into people’s skin to fight wrinkles or boost hair growth. Another company, Life Biosciences, is preparing to test whether reprogramming eye cells can treat blindness.

Article by Antonio Regalado, translated from English by Kozi Pastakia.

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