Rejuvenating and extending life are the promises spearheaded by a biotech company with a technology called reprogramming. What is initially being tested in mice feeds the hope that older people could one day turn back their biological clocks with an injection and literally become younger.
Rejuvenate Bio is the name of the biotech start-up from San Diego that is currently making headlines with the news. The company’s research was released last week in a Preprint paper on the BioRxiv website released. It has not yet been checked by external experts.
Risky Rejuvenation Elixir
The so-called reprogramming technique, which transforms cells into a younger state, has garnered hundreds of millions of investments in recent years as a potential elixir of rejuvenation. Scientists had previously proven that the technology works with individual cells in the laboratory. The next step is to show whether the rejuvenation effect also works in living animals. Rejuvenate now wants to have overcome this hurdle.
Noah Davidsohn, Rejuvenate’s scientific director, says the company used gene therapy to introduce three powerful reprogramming genes into the bodies of elderly mice, roughly the same age as a 77-year-old human. After treatment, their remaining lifespan doubled: the treated mice lived an additional 18 weeks on average, while the control mice died after nine weeks. Overall, the treated mice lived about seven percent longer.
Although the increase in lifespan has been modest, the company says the research is evidence of age reversal in an animal. “This is a powerful technique, and here’s proof that it works,” says Davidsohn. And it could potentially be used in an aging population.
Researchers unaffiliated with the company, while calling the study a potential milestone, warn that full-body rejuvenation using gene therapy remains a poorly understood concept with major risks: “It’s a nice intellectual exercise, but I would shy away from doing anything remotely similar to a human being,” says Vittorio Sebastiano, a professor at Stanford University. One risk is that the powerful programming process can cause cancer – as has already been observed in mice.
Science of Reprogramming
In the laboratory, reprogramming works by exposing individual cells to a series of three or four proteins that are typically active in early-stage embryos. After several days of treatment, even old cells transform into young stem cells. Japanese biologist Shinya Yamanaka shared the 2012 Nobel Prize in Medicine with British scientist John Gurdon for discovering the reprogramming recipe.
“Everyone in the research community knows that the killer experiment is treating normal mice and seeing if lifespan increases or overall health improves,” says Martin Borch Jensen, founder of Impetus Grants, an organization which provides financial means for aging research.
As several years passed after Yamanaka’s discovery with no such experiment, doubts grew as to whether rejuvenating cells in living animals would work. Hopes that science could create super-durable mice began to fade.
However, last year the first study was published by a team working with mice that were genetically engineered from birth to produce Yamanaka’s special factors in their bodies. While this team at the National Institute of Health and Medical Research found a trend towards longer lifespans, the report was considered preliminary.
effect in a short time
In the case of the Rejuvenate research, the treatment was now delivered using gene therapy. Viruses are used that have been specially developed to introduce genes into cells. Davidsohn says this is very similar to the actual medical treatments people might one day receive.
Mice live only a few months in the wild, but can live two to three years in the laboratory. The mice in the latest experiment were already 124 weeks old when they received the drug – that is, close to the end of their lives. According to Davidsohn, the treated mice not only survived significantly longer, but they also performed better on measures of general health.
The fact that the life expectancy of mice can be medically extended in a targeted manner is not unprecedented. A US government program that tests drugs for their effects on longevity has shown in the past that various compounds, including the drug rapamycin, could extend the life of mice by 5 to 15 percent.
However, in this case, the mice would have to take these drugs for much of their lives, while reprogramming would have short-term effects. “It’s as if you could do nothing your whole life and still have a benefit,” says Davidsohn.
What’s next?
Rejuvenate is currently developing gene therapy drugs for pet dogs and humans, including one to treat heart failure. But Davidsohn says that over the long term he believes it will be possible to rejuvenate people. “I wouldn’t work on it if I didn’t believe in it,” he says.
Much more information is needed to find out exactly what changes – positive and negative – the reprogramming genes cause in the mice. “I’d love to see another research group do something similar and take a closer look at what’s actually happening,” says Borch Jensen.
Stem cell researcher Vittorio Sebastiano says the life-prolonging effect reported by Rejuvenate may be due to changes in a single organ or group of cells, rather than an overall rejuvenating effect in mice. Among other shortcomings in the research, Rejuvenate did not carefully document which and how many cells were altered by the genetic treatment. So there are still questions and some doubts about the research of the start-up.
Meanwhile, several companies are moving forward with plans for reprogramming drugs. However, many concentrate on recognized diseases or limit their efforts to the rejuvenation of certain organs. For example, Turn Bio, a company co-founded by Sebastiano, hopes to inject reprogramming factors into people’s skin to fight wrinkles or restart hair growth. Another company, Life Biosciences, is preparing to test whether reprogramming cells in the eye can treat blindness.
(bsc)
