Biotechnology: This company claims to have extended the lives of mice by reprogramming their cells

A small biotech company, Rejuvenate Bio, claims to have used a technology called “cell reprogramming” to rejuvenate old mice and prolong their lives. A result that suggests that one day the elderly will be able to see their biological clock turned back 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life extension claim made by Rejuvenate Bio was cited in a preliminary article posted on the BioRxiv website and was not peer-reviewed.

The technique of cell reprogramming to return cells to a more youthful state has been the subject of investments of hundreds of millions of dollars. Scientists had already shown that it worked in individual cells in the laboratory and are now trying to determine whether the rejuvenating effect also works in live animals.

The Rejuvenate Bio article is widely anticipated proof that this method can indeed 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 to the bodies of mice whose age matched that of a 77-year-old human.

After treatment, their life expectancy doubled, says the San Diego-based company. The treated mice lived 18 weeks longer, on average, while the control mice died within 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’s the embodiment of the concept”, enthuses Noah Davidsohn. “I wanted to show that it’s really something that 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 enormous risks. “It’s a good 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 can 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 over 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 was awarded to a biologist for his work in reprogramming adult cells

The discovery of the recipe that led to reprogramming earned Japanese biologist Shinya Yamanaka the Nobel Prize in 2012.

Four years later, scientists at the Salk Institute experimented with 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 anti-aging intervention, was to show that it could also prolong 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.

After several years without obtaining such a result, doubts began to arise about the effectiveness of the method. Hopes 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, working at the National Institute of Health and Medical Research, found a trend towards longer life expectancy, but this report was considered preliminary.

In the case of Rejuvenate Bio’s work, the treatment was administered using gene therapy – a virus specially developed to transfer genes into cells. According to Noah Davidsohn, this makes the treatment similar to real medical treatments that people might receive.

Rats live only a few months in the wild, but can survive two to three years in the laboratory. Those who participated in the last experiment were already 124 weeks old when they received the medicine, that is, they were almost at the end of their lives. According to Noah Davidsohn, the treated mice not only survived significantly longer, but also performed better in terms of overall health.

The magnitude of observed life span 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 most of their lives, while reprogramming has immediate effects. “It’s like you can’t do anything your whole life and still get the benefits,” insists Noah Davidsohn.

The next step: extending the lifespan of humans?

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

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

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

Several companies are now pursuing their reprogramming projects, but opt ​​for recognized pathologies and focus their efforts on specific organs.

Turn Bio, a company co-founded by Vittorio Sebastiano, for example, hopes to inject reprogramming factors into people’s skin to fight wrinkles or stimulate 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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