The Benjamin Button effect: scientists unlock the key to reversing aging

The Benjamin Button effect: scientists unlock the key to reversing aging

PARIS — Barbra Streisand loved her dog Samantha, aka Sammy. The fluffy white thoroughbred Coton de Tulear was even present on the steps of the Elysée Palace, the official residence of the French president, when Streisand was awarded the Legion of Honor in 2007.

As the singer and actress explains inThe New York Times in 2018, she loved Sammy so much that, unable to bring herself to see him die, she had the dog cloned by a Texas firm for the modest sum of $50,000 just before dying in 2017, at the age of 14. this is how Barbra Streisand became the proud owner of Miss Violet and Miss Scarlet, two puppies who are the spitting image of the late Samantha.

It may seem like a joke, but there is a deeply disturbing fact that David A. Sinclair, professor of genetics at Harvard Medical School, points out in his book. Why we age – and why we don’t have to. It is that the cloning of a old dog led two Young puppies.

It proves that DNA – ours as well as Sammy’s – has everything it takes to restore lost youth. This is a property that could be used to “reverse” aging without having to go through the problematic step of cloning.

The idea is based on the identification of the body’s “reset” button. And aging specialists all have the same good news to announce: this button has been found.

A 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 specializing in stem cell research who was awarded the 2012 Nobel Prize in Medicine.

If this all sounds a bit too sci-fi, American biotech company Altos Labs, which was just founded earlier this year, received a check for three billion dollars from billionaires Yuri Milner and Jeff Bezos. . Not bad for a start-up. But it is a start-up with a very promising technology: cell reprogramming, which is none other 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, changed it from being a differentiated cell (nerve , blood, etc.) to be a pluripotent stem cell, i.e. which can then redevelop into any type of cell.

A French breakthrough

It didn’t take long for Yamanaka’s colleagues to profit from his incredible discovery. In 2011, the French researcher Jean-Marc Lemaître, who worked at the Institute of Functional Genomics of the University of Montpellier (which has never received the same financial support as the American biotech Altos Labs!) was the first to prove experimentally, on human tissues, that cellular aging is 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 cell aging. It suffices to interrupt the process before reaching this stage to trigger the series of gene reactions that counter cellular aging.

But that’s not all. Since the pioneering work of Lemaître, biologists on both sides of the Atlantic have shown that what is 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 magazine “Cell”, a professor from the Salk Institute (San Diego, California) Juan Carlos Izpisua Belmonte revealed the more than promising results recorded on genetically modified rodents.

The rodent genome had been enriched with the Yamanaka factors as well as a small piece of additional genetic code, corresponding to a kind of on-off switch. Controlling the activation of the four genes, this “promoter” was itself activated only if the mouse ingested an antibiotic, doxycycline more precisely.

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 one-way process, as we thought. We can slow it down and even reverse it,” he announced triumphantly. In a very similar experiment, Jean-Marc Lemaître obtained a more modest lengthening, of 15%, but thanks to a single dose of doxycycline. And above all, insists the French researcher, this “additional” lifespan has proven to be free of all age-related diseases: osteoporosis, arthritis, pulmonary or renal fibrosis, etc.

White hair turns dark

Genetic modification of mice is a common practice in laboratories. But must we do the same with humans to obtain the same result? There was a public outcry in 2018 when Chinese researcher He Jiankui “gave birth” to twins with doctored genomes – the first genetically modified children in history – in an attempt to give them resistance to HIV.

Our view of “GMO babies” may change over the next few decades. But whether it changes or not, it won’t be necessary to go that far to do cellular reprogramming in humans. A simple vaccine will probably do the trick.

The Covid-19 pandemic has made the public aware that a vaccine – whether RNA or DNA – can be used as a vector to introduce genetic material into the human body. Messenger RNA vaccines from BioNTech and Moderna do this, but many other “viral vectors” exist, such as adeno-associated viruses (AAV), small, non-pathogenic DNA viruses commonly used in molecular biology to carry one or more “genes of interest”. On paper, nothing prevents 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 received one or more injections of this viral vector responsible for carrying the Yamanaka factors within us. Nothing would change in our body yet, as the Yamanaka Factors were programmed to remain silent until activated by the Promoter. So we would continue to age normally. The passage of years would no longer be irreparable!

We can slow aging and even reverse it

Indeed, as soon as we would begin to feel their first adverse effects, say around our mid-40s, we would be prescribed a month’s course of doxycycline. And then—but only then—youth therapy would kick in. White hair disappeared, wounds healed faster, wrinkles faded, organs regenerated, glasses became useless… “Like Benjamin Button”, wrote David Sinclair, “you would feel the sensations of a 35-year-old man. Then 30. Then 25. But unlike Benjamin Button, you won’t go beyond that limit, because the statute of limitations would be interrupted… You would be about two decades younger biologically, physically and mentally, without have lost none 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 sections of society and will not be without posing delicate problems for a planet with limited resources. But who among us, once reached a certain age, would not dream of regaining our lost youth, while retaining the “benefits of experience”?

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