06 September 2021

We're going to look

Silicon Valley startup Altos Labs is looking for ways to prolong youth

Elena Likhanova, RB.RU

In October 2020, a group of scientists gathered at Yuri Milner's mansion in Los Altos Hills, above Palo Alto, to take part in a two-day scientific conference. The others connected via video link. The event discussed how to use biotechnology to make people younger.

According to sources close to the situation, this is how a new ambitious startup Altos Labs appeared.

At the beginning of 2021, the company was registered in the USA and the UK. It is planned to create several divisions in the United States (San Francisco Bay Area and San Diego), the United Kingdom (Cambridge) and Japan. Altos Labs is already recruiting a large staff of university scientists, attracting them with generous salaries and promises that they will be able to freely conduct research on cell aging and reverse this process.

Several people learned from startup representatives that among its investors is Jeff Bezos, the richest man in the world, who recently visited space. Yuri Milner and his wife Yulia confirmed through a representative that they invested in Altos Labs through the fund.

Altos Labs can be compared to Calico Labs, a company that deals with life extension. Google co-founder Larry Page announced its creation in 2013. Like Altos Labs, Calico has also attracted leading scientists and given them generous budgets, although it is unclear whether it has made significant progress. Calico has also opened a laboratory that deals with reprogramming. This year she published the first preprint on this topic.

Among the scientists said to be joining Altos Labs is Juan Carlos Ispisua Belmonte, a Spanish biologist at the Salk Institute in La Jolla, California, who gained fame through research on mixing human and monkey embryos and predicted that human life expectancy could be increased by 50 years. The Salk Institute declined to comment.

Also participating in the project will be Steve Horvath, a professor at the University of California at Los Angeles and the developer of a "biological clock" that can accurately measure human aging. Shinya Yamanaka, who received the Nobel Prize for the discovery of reprogramming technology, will become an unpaid senior researcher and head the scientific advisory board of the company.

His discovery is that with just four proteins, now known as "Yamanaki factors," cells can be instructed to return to a primitive state with the properties of embryonic stem cells. By 2016, the Ispisua Belmonte laboratory applied these factors to live mice, achieving signs of age change. Because of this, the scientist calls reprogramming a potential "elixir of life".

The results of such experiments on mice, while promising, were also frightening. Depending on the extent of reprogramming, some mice developed ugly embryonic tumors called teratomas, although others showed signs of tissue rejuvenation.

"Despite the fact that there are many obstacles to overcome, there is a huge potential," Yamanaka wrote in an email, confirming that he is cooperating with Altos Labs.

Midlife crisis?

They say that young people dream of becoming rich, and rich people dream of becoming young. Such people as Milner (he is 59 years old) and Bezos (57 years old) could well face this paradox. Now Forbes estimates Bezos as the richest man in the world with a net worth of about $200 billion. Milner's fortune is estimated at $4.8 billion.

Bezos Expeditions, the investment company of the founder of Amazon, did not respond to an email asking for comment.

People familiar with the history of the creation of Altos Labs say that initially Milner's interest in reprogramming was philanthropic. After the meeting at his home, the Milky Way Research Foundation, sponsored by Milner, provided several longevity researchers with grants for a period of three years, $1 million per year each.

The applications were considered by an advisory board, which included Yamanaka and Jennifer Dudna, who shared the prize in 2015, and then the Nobel Prize in 2020 for the joint discovery of CRISPR genome editing.

However, around 2021, it was decided to accelerate the progress of research and establish a well-funded company, which is now called Altos Labs. The project was headed by Richard Klausner, former head of the US National Cancer Institute, and now an entrepreneur. Previously, he helped create projects such as Juno Therapeutics and the Grail cancer testing service, and is known for major investments in new biotechnologies.

According to the registration application of Altos Labs, Klausner became CEO of the new company. He did not respond to attempts to contact him by email and phone. 

Now several startups are engaged in reprogramming technologies: Life Biosciences, Turn Biotechnologies, AgeX Therapeutics and the British Shift Bioscience. However, no one has yet conducted clinical trials of the methods in humans.

"Investors are raising hundreds of millions of dollars to invest in reprogramming to rejuvenate parts or the entire human body," says David Sinclair, a Harvard researcher who reported last December that he was able to restore the vision of mice using this technology.

Sinclair describes the field as "nascent," but believes it has unique perspectives.

"What else can be done to change the age of the body? "What is it?" he asks. "In my lab, we mark the main organs and tissues, such as skin, muscles and brain, to see which ones we can rejuvenate." Sinclair says he is not an employee of Altos Labs, but he spoke at the 2020 meeting and applied for an award from the Milky Way Research Foundation.

Scientific business

Altos Labs has not yet made an official announcement, but this year it was registered in Delaware. Will Gornall, a professor at the business school at the University of British Columbia, who reviewed the securities information disclosed in June, indicates that the company has raised at least $270 million. In addition to Bezos and Milner, the company may have other investors from wealthy representatives of the technology sector and venture capitalists.

Other Altos Labs employees include Peter Walter, whose laboratory at the University of California, San Francisco is developing a molecule that has a beneficial effect on memory. Also joining the team is Wolf Rake, a reprogramming specialist who recently resigned as director of the Babraham Institute in the UK. Walter and Rake declined to comment.

At least initially, Altos Labs will fund researchers without expecting immediate results or revenue.

Altos Labs attracts university professors, offering salaries like sports stars from $1 million a year plus a share in the capital, as well as the absence of hassle with applying for grants. One researcher who confirmed that he accepted Altos' offer, Manuel Serrano from the Institute for Biomedical Research in Barcelona, Spain, said that the company would pay him 5-10 times more than he earns now.

"The philosophy of Altos Labs is research based on curiosity. This is what I know and love to do," says Serrano, who plans to move to Cambridge to work at Altos Labs. — In this case, thanks to a private company, we have the freedom to be bold and explore. So it will make me younger."

Any cure for such a serious disease as aging can cost billions. But Altos Labs does not expect to earn immediately.

"The goal is to understand how rejuvenation happens," Serrano says. — I would say that the idea of earning income in the future exists, but this is not the immediate goal."

In 2013, Serrano was the first scientist to genetically engineer mice to produce "Yamanaka factors." All of them developed tumors when their cells returned to the embryonic stage. Nevertheless, the work demonstrated that time can be reversed inside a living animal. "You introduce factors and they work magic. It's very simple experimentally, even if it's not clear," says Serrano.

The main question now is how to manage reprogramming to see if it can safely rejuvenate animals without killing them, and whether it will be possible to run it with conventional drugs, and not with the help of genetic engineering.

"To me, the clinical use of Yamanaka factors looks unrealistic," Serrano says. — This involves the introduction of genes, some of which are oncogenic. It is difficult to coordinate this procedure with regulatory authorities."

Some believe that state institutions will not be able to provide investments in anti-aging methods quickly enough. Martin Borch Jensen, Director of Science at Gordian Biotechnology, says that this year he will issue grants worth $20 million from sponsors to accelerate research. The program was named Impetus — from the English "Impulse".

"We're betting a lot on this," says Jensen. — We are discussing: "Let's see if reprogramming works. Let's see if molecular clocks can be biomarkers." If it works, the consequences will be spectacular."

Too early?

Some researchers wonder if reprogramming will become a technology that will help benefit from hundreds of millions of commercial investments. Alejandro Ocampo, who used to work in the laboratory of Ispisua Belmonte at the Salk Institute, and is now a professor at the University of Lausanne in Switzerland, is skeptical that reprogramming technology will become a medicine in the near future.

"I think this is a serious concept, but there is a lot of hype around it. Its application is still far away," says Ocampo. "It's risky, and it won't be possible to use it to treat people soon."

One of the problems is that reprogramming not only makes cells behave as if they are younger, but also changes their essence — for example, turning a skin cell into a stem cell. It is because of this that the technology is still too dangerous to be tested on humans yet.

Ocampo also worries that there is too much money in this area and too many companies are trying to enter it. "I think it's happening too fast. I do not know if we need to have five or eight companies that are engaged in reprogramming - it looks too fast," he says. — How many in vivo reprogramming works have already been done? About the same as the companies."

On the other hand, this method has an undeniable, reproducible effect in laboratory experiments when applied to individual cells.

"You can take a cell from an 80-year-old person and change the age in a test tube to 40 years. There is no other technology that could do this," Ocampo says.

Reprogramming is considered a key process that occurs naturally when a fertilized egg turns into an embryo and nine months later becomes a baby. Somehow, the DNA of the parents is cleaned, updated and restarted. Ocampo believes that reprogramming can be called "the experiment that was reproduced the most", because trillions of baby animals were born over a billion years.

In addition, Altos Labs will use related technology to measure the relative age of a cell or a person. The biological clock method, first developed by Horvath, provides for the measurement of "epigenetic" marks on genes. They "turn on" and "turn off" genes, but as a person ages, their structure becomes disorganized.

Such a biomarker of aging would help to quickly measure the effectiveness of drugs for prolonging life or rejuvenation.

Young and rich

It is believed that Bezos has long been interested in longevity research. Previously, he invested in the anti-aging project Unity Biotechnology. Although Technology Review could not specify the size of Bezos' stake in Altos Labs, the billionaire is probably thinking about getting older.

In his latest message to Amazon shareholders, Bezos quoted from a book by biologist Richard Dawkins: "Preventing death is a goal that requires work to achieve... Living beings who do not show activity to prevent this alignment eventually merge with their environment, and cease to exist as autonomous entities.  That's what happens when they die."

Bezos meant that nations, companies and individuals must fight to remain distinctive, original and unique. One way to do this is to turn back time by regaining your youth.

Portal "Eternal youth" http://vechnayamolodost.ru

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