“You’re not getting back in,” a conference official told the crowd of PhD students and postdocs who began milling around the doors after being escorted from the room.
The brouhaha shows how excitement is building as researchers uncover the secrets of life and some, like Belmonte, claim they will eventually use molecular technology to radically extend it, by 40 years or more, he has said.
The meeting in Boston wasn’t even about defeating aging. It was a convention of specialists on stem cells. The idea of these researchers is to mimic, in the lab, the way human cells develop during pregnancy into their specialized roles. Their results already include organoids that grow to resemble fetal brains and manufactured retina cells that have been injected into the eyes of blind people, with promising early results.
However, while the stem-cell researchers want to copy the molecular programs that bodies use to develop, new discoveries could eventually let researchers press rewind on that same process, and thus make old animals younger.
“This is almost the ultimate feat for an engineer: the reversal of the life process,” said Haifan Lin, the Yale University cell biologist who is president of the International Society for Stem Research, which organized the meeting.
And that explains the boisterous attendees, Lin told me later in the day. “I apologize if there was a disruption. But take a step back,” he added. “It’s a good sign for this field that there is so much interest. It’s a hot topic. Hotter than we expected.”
Altos Labs
After witnessing the roiling crowd of researchers on Friday, it’s easy to imagine riots in the streets if science ever actually discovers the cure for aging — which at first, would surely be an ultra-expensive remedy for the rich.
Just how close science is to age-reversal is what the crowd had come to hear. That, and to catch a glimpse of Izpisua Belmonte, the bald, squint-eyed figurehead of a new technological concept for reversing aging called “cellular reprogramming.”
The Spanish scientist, usually seen in his signature blue sport coat, has led efforts to try to rejuvenate entire animals, or parts of them, since 2016 when he reported that sick mice lived 30% longer than expected after receiving a cocktail of special “reprogramming” proteins.
His ideas rocketed to new prominence two years ago when Izpisua Belmonte was recruited by Altos Labs, a startup company set up by billionaires to pursue what they called rejuvenation technology. Altos, with an eye-popping $3 billion in startup funds, is among the best funded biomedical startups of all time, if not the richest of them all.
You can think of Altos as a biomedical version of OpenAI, the software company releasing intelligent-seeming chatbots. Like OpenAI, Altos has amassed technical talent, financial resources, and attracts overwhelming hype as it pursues technology that could fundamentally transform society.
Altos has ample funding to investigate rejuvenation and, if possible, corner the market on the most promising approaches. The company has established three institutes, in Cambridge, UK, San Diego and in the San Francisco Bay area. Wolf Reik, leader of Altos’ Cambridge institute, also spoke during the Boston event and mentioned the “very beautiful building” Altos occupies there. He showed a photo of workers lined up in an atrium, who he referred to as “many happy people. Happy people in lab coats.”
Reik was kidding, but not really. Unlike workers at universities, Altos researchers don’t have to spend time applying for grants. Altos pays its top staff salaries of one million dollars and more and doubles what junior scientists can earn. It’s an enviable place to do science, but one with a commercial mission. Reik said that last month his group had filed its first patent application on its discoveries.
During his talk, Belmonte, who heads Altos’ San Diego outpost, reviewed evidence—both published and unpublished—that he says supports the phenomenon of rejuvenation or de facto age-reversal of tissues.
It all has to do with the “epigenome”—the series of chemical controls on and around our genes that determine which are active, and which are not. These controls can modulate individual genes, or large stretches of chromosomes, putting open for business signs some areas, while others are tightly wound and packed away, like a pair of earphones jammed deep in a pocket.
Broadly speaking, Belmonte says he believes “dysregulation” of these control systems is a fundamental process that underlies aging and many diseases.
To rejuvenate cells, Belmonte has been exploring a method of resetting the epigenome called ‘reprogramming.’ During his talk, Belmonte raced through examples of how reprogrammed cells become more resilient to stress and damage, and on the whole appear to act younger.
In one experiment, for example, he says his lab gave mice ultra-high doses of the pain-killer acetaminophen that are usually fatal. Yet if the mice are given a reprogramming treatment, which consists of special proteins called Yamanaka factors, half will survive. “We reduce the mortality about 50%, more or less” he says.
He also described experiments where mutant mice were allowed to gobble high-fat food. They became obese, but not if they were given a brief dose of the same reprogramming proteins. Somehow, he said, the procedure can “prevent the increase in the fatty tissue.”
So how is it that reprogramming can have such very different, but very helpful effects on mice? That is the mystery he’s trying to unravel. “I could go on and on and on about the…examples we’ve been using in the lab these last years,” Belmonte said. “You have to agree with me that this is a little strange, having one medicine that can cure all these things. “
So is this what the fountain of youth looks like? Many researchers remain skeptical and some say Belmonte’s dramatic claims should come with more proof. On Twitter, biologist Lluis Montoliu cautioned against “unjustified hype” and said researchers should “wait to see” scientific publications.
Junk DNA
Even as police kept onlookers away from the door, Belmonte unspooled evidence for what he says is a second way to produce rejuvenation results, one that Altos is also pursuing.
Some researchers suspect aging could cause our cells to lose control over some of so-called junk DNA that makes up 45% of our genomes and which is the residue of genes known as transposable elements, or jumping genes, which are able to copy themselves, a bit like a virus.
The role of these parasitic genetic elements remains mysterious. They may be useful in some ways, helping us evolve by mix-and-matching pieces of genetic code, but they’re also eyed as the cause of health problems.
“There’s a good side to it, but so far it’s mostly bad,” says Lin, whose lab has studied how our cells continuously try to suppress transposable elements.
It’s known that as we age, our ability to silence these elements appears to gradually wane, for several reasons including changes to our epigenome, which helps to keep them in check. Some researchers describe a nearly constant battle between jumping genes and the epigenome, a battle cells start to lose as the years go by.
To test the connection, Belmonte told the audience he has been using genetic drugs to artificially suppress these elements, especially one called LINE-1, which on its own accounts for around 18% of the human genetic code.
After doing so, he claims, he can get very similar rejuvenation effects as with reprogramming technology. For instance, according to unpublished data, Belmonte says the cartilage of mice can be “rejuvenated” either by reprogramming or by silencing the effects of transposable elements.
These big claims will need to be confirmed, but one scientist I spoke to said he thought Belmonte may well have the tiger by the tail. “Working at Altos, they are under pressure to deliver,” says Rudolf Jaenisch, a professor at MIT and the Whitehead Institute. “But he clearly has the right questions in mind. These transposable elements are underappreciated in aging and how they shape the genome.”
So has Altos gotten closer to the fountain of youth—and to a drug intervention that could turn back the clock? Who knows. Certainly not all the scientists who couldn’t get into the talk.
When he heard what Belmonte had discussed, Lin, the president of the stem cell society, said he was disappointed to have missed it. “Gee, I wish I was there,” said Lin. “But there were too many people in the room. It violated the fire code.”
