Billion-dollar start-up

Its name sounds like a Japanese techno-thriller title: "The Yamanaka factors". But Shinya Yamanaka is not a fictional character. He is a scientist specialized in stem cell research who received the 2012 Nobel Prize in Medicine.

If all this sound a bit too science-fictional, you should know that the U.S. biotech company Altos Labs, which was just founded early this year, received a check of three billion dollars from billionaires Yuri Milner and Jeff Bezos. Not bad for a start-up. But this is a start-up with a very promising technology — cellular reprogramming, which is nothing more than the name given by biologists to the famous "reset" button.

In 2006-2007, Yamanaka announced to the scientific community that he had discovered a combination of four genes — Oct4, Klf4, Sox2 and c-Myc — which, when injected into a cell, induces it to go from being a differentiated cell (nerve, blood, and so on) to being a pluripotent stem cell, i.e., one that can subsequently redevelop into any cell type.

Very promising results

A French breakthrough

It didn't take long for Yamanaka's colleagues to take advantage of his amazing discovery. In 2011, French researcher Jean-Marc Lemaître, who worked at the Institute of Functional Genomics at the University of Montpellier (which never received the same financial support as American biotech company Altos Labs!) was the first to experimentally prove, on human tissues, that cellular aging was a reversible process. He and his team succeeded in transforming aging or senescent human skin cells back into young skin cells.

The process has since been improved, since it is no longer necessary to go through the stage of pluripotent cells — which can degenerate into cancerous cells — to reverse cellular aging. Interrupting the process before reaching this stage is enough to start the series of gene reactions that counter cellular aging.

But that's not all. Since Lemaître's pioneering work, biologists from both sides of the Atlantic have shown that what was possible at the level of the cell is also possible at the level of the organism as a whole. As is often the case, they used mice as guinea pigs. At the end of 2016, in a famous study published by the "Cell" magazine, a professor at the Salk Institute (San Diego, California) Juan Carlos Izpisua Belmonte revealed the more than promising results recorded on genetically modified rodents.

The rodents' genome had been enriched with the Yamanaka factors as well as a small piece of additional genetic code, corresponding to a sort of on-off switch. Controlling the activation of the four genes, this "promoter" was itself activated only if the mouse ingested an antibiotic — the doxycycline to be precise.

By prescribing this molecule (and thus activating the Yamanaka factors) two days a week throughout the life of the mice, Belmonte and his team increased their lifespan by 40%. "Aging is no longer a unidirectional process, as we thought. We can slow it down and even reverse it," he announced triumphantly. In a very similar experiment, Jean-Marc Lemaître has obtained a more modest lengthening, of 15%, but thanks to a single dose of doxycycline. And above all, insists the French researcher, this "extra" lifespan proved to be free of all age-related diseases: osteoporosis, arthritis, pulmonary or renal fibrosis, etc.

White hair turns dark

The genetic modification of mice is common practice in labs. But should we do the same with humans to get the same result? There was public outcry in 2018 when Chinese researcher He Jiankui “gave birth” to twins with tampered genomes — the first genetically modified children in history — with the objective of giving them resistance to HIV.

How we view "GMO babies" may change over the next few decades. But whether it changes or not, it will not be necessary to go that far to do cell reprogramming in humans. A simple vaccine will probably do the trick.

The Covid-19 pandemic made the public aware that a vaccine — whether RNA or DNA — could be used as a vector to introduce genetic material into the human body. BioNTech's and Moderna's messenger RNA vaccines do this, but many other "viral vectors" exist, such as adeno-associated viruses (AAVs), small, non-pathogenic DNA viruses commonly used in molecular biology to carry one or more "genes of interest”. On paper, there is nothing to prevent these genes of interest from being precisely those highlighted by Yamanaka.

And this is what our near future could look like. Around the age of 30, when we are — alas, only temporarily! — at the peak of our mental and physical fitness, we would receive one or more injections of this viral vector responsible for carrying Yamanaka's factors into us. Nothing would change in our body yet, as the Yamanaka factors have been programmed to remain silent until activated by the promoter. So we would continue to age normally. The passing of the years would no longer be irreparable!

We can slow down aging and even reverse it

Indeed, as soon as we would start to feel their first undesirable effects, let's say in our mid-forties, we would be prescribed a month's treatment with doxycycline. And then — but only then — would the youth therapy kick in. White hair disappearing, wounds healing faster, wrinkles fading, organs regenerating, glasses becoming useless... "Like Benjamin Button," writes David Sinclair, "you would experience the sensations of a 35-year-old. Then 30. Then 25. But unlike Benjamin Button, you would not go beyond that limit, because the statute of limitations would be interrupted... You would be about two decades younger biologically, physically and mentally, without having lost any of your knowledge, wisdom or memories."

Of course, such a possibility, if it becomes a reality and especially if it becomes widespread, will revolutionize large parts of society and will not be without its own tricky problems for a resource-limited planet. But who among us, once we reach a certain age, wouldn't dream of regaining our lost youth, while retaining the "benefits of experience"?