“Within two decades we will be able to prevent aging”

An American startup, with a staggering initial budget of some €2.7bn, has been secretly recruiting some of the world's top scientists, including four Nobel Prize winners, in recent months.

The multinational, called Laboratorios Altos, was finally presented to the world on January 19, without revealing its splendid sources of financing, but with the declared objective of ensuring that human beings live longer with health.

Some information, neither confirmed nor denied by the company, suggests that much of the money comes from the pocket of the richest man in the world, the American tycoon Jeff Bezos, founder of Amazon.

The British newspaper

summed it up directly like this: "Jeff Bezos makes signings in search of eternal youth."

The Spanish scientist Juan Carlos Izpisua is one of those signings.

The researcher, born in Hellín (Albacete) 61 years ago, denies the simplistic idea that Altos is a project by a billionaire to try to be immortal.

"That simply is not true.

Our interest is to advance in this area of ​​knowledge and open the field wide, so that, over time, everyone can benefit, ”he says.

Izpisua will direct one of the three Altos institutes, the one in the US city of San Diego.

The other two centers will be in Cambridge (UK) and in the San Francisco region (USA).

The new company was born shrouded in secrecy.

This newspaper has requested to interview the four Spanish scientists signed by Altos, but the company only allows Izpisua to speak, who answers questions from EL PAÍS by email.

“The idea behind our research is not to make human beings live another 100 or 1,000 years.

If we were able to lengthen life without improving the quality of those years, it would not only be morally doubtful, but I wonder what would be the use of it”, says Izpisua.

"Our priority objective is to make people live healthier lives for longer and reverse the disease in patients of any age," adds the researcher, who announces imminent experiments with monkeys.

Our goal is not to make human beings live another 100 or 1,000 years.

Juan Carlos Izpisua

The official budget of Altos comfortably doubles the 1,120 million per year of the largest public science body in Spain, the CSIC.

The company's signings are stellar.

Its board of directors includes American chemist Jennifer Doudna, winner of the 2020 Nobel Prize in Chemistry;

the American engineer Frances Arnold, Nobel Prize in Chemistry in 2018;

and the virologist David Baltimore, Nobel Prize in Medicine in 1975 and also an American.

The Japanese Shinya Yamanaka, Nobel Prize in Medicine in 2012, is scientific advisor to the new multinational.

The young cells of a tiny human embryo, during the first few days, are still capable of becoming any kind of tissue, but they soon become specialized to give rise to the different organs of the body: brain, lungs, skin, heart, kidneys.

Yamanaka discovered that this seemingly inexorable process could be reversed.

In 2006 he invented a technique to rewind adult cells back to the embryonic state.

His work showed that cells have the ability to rejuvenate in the laboratory, basically thanks to the activation of four genes, responsible for the production of four reprogramming molecules known as Yamanaka factors.

This cell reprogramming will be one of the great lines of research in Altos.

The company has also signed Manuel Serrano and María Abad, the two Spanish scientists who in 2013 managed to apply the Yamanaka technique to animals for the first time, when they worked at the National Cancer Research Center in Madrid.

Serrano and Abad managed to rewind adult cells from living mice and transform them into embryonic stem cells, opening the door to the regeneration of damaged organs.

The problem is that this pioneering reprogramming caused a multitude of tumors in rodents.

The researcher María Abad, still at the Vall d'Hebron Institute of Oncology, in Barcelona. ”la Caixa” Banking Foundation

Izpisua's team at the Salk Institute (USA) circumvented the cancer hurdle in 2016 by activating the four rejuvenating genes intermittently, instead of constantly.

His mice lived 30% longer, despite the fact that they had also been genetically modified to suffer premature aging and save time in the experiments.

This Monday, Izpisua presents its latest results in the specialized journal

.

His group and other Genentech biotechnology researchers have intermittently activated the four genes in healthy middle-aged mice, for a period equivalent to 35 human years, also observing "rejuvenating effects" in different tissues, such as the kidneys and the skin.

Manuel Serrano's team, still at the Barcelona Biomedical Research Institute, obtained similar results in a study published last week in the journal

.

"We can program and rejuvenate the tissues and organs of animals with different pathologies, as well as rejuvenate their cells," says Izpisua.

“Conceptually, I see no reason why we should not think that similar results can be obtained in humans, both in terms of improving the course of many diseases and increasing the length and quality of life.

In fact, we have already demonstrated it with human cells in vitro”, adds the researcher.

We can program and rejuvenate the tissues and organs of animals with different pathologies, as well as rejuvenate their cells

Juan Carlos Izpisua

The Izpisua team has devised an ingenious experiment.

The mice in their new study are genetically engineered to have extra copies of the four genes, which are only activated if the animals drink water with a specific drug, the antibiotic doxycycline, that works like a switch to increase or decrease rejuvenation factors.

It is an impossible approach to transfer to humans, but Izpisua announces that, in the next experiments, his team will try to rejuvenate monkeys by intermittently increasing Yamanaka factors with messenger RNA technology, popularized by covid vaccines, or with chemical compounds.

Izpisua explains that the main objective of his latest study was to certify the safety of the rejuvenating treatment in the long term and to understand the molecular changes caused.

In order to analyze the tissues, the researchers had to sacrifice the mice, so they have not yet been able to show that their strategy does indeed increase longevity.

"These experiments are ongoing with other animals and take time, given the natural longevity of a mouse without specific pathologies," details the scientist.

His research has been funded by the Dr. Pedro Guillén Foundation and by the San Antonio Catholic University of Murcia, a private institution that has already participated in Izpisua's controversial work to create 132 embryos with a mixture of monkey and human in China, whose objective was illuminate embryonic development.

The Spanish scientist invites to "conceptualize the disease as a process of cellular deterioration that is reversible".

Izpisua reminds that low-calorie diets have a beneficial effect on health.

His group has shown that this positive effect is related to a decrease in tissue inflammation, which is a common feature in many diseases and is especially present during ageing.

"Finding molecular targets that reduce inflammation can lead us to develop drugs that mimic the beneficial effect of calorie restriction and help slow down or prevent the progression of many diseases, as well as cellular aging," says the researcher.

Disease must be conceptualized as a process of cellular deterioration that is reversible

Juan Carlos Izpisua

Izpisua is optimistic.

"I am convinced that within two decades we will have tools that not only treat symptoms, but can predict, prevent and treat disease and aging through cellular rejuvenation," he says.

Altos does not detail its investors.

Izpisua only confirms ARCH Venture Partners, an American venture capital firm specialized in financing biomedical companies at the forefront of knowledge.

The fourth Spaniard signed by Altos is Eduardo Moreno, another expert in the molecular ins and outs of aging, who until now was at the Champalimaud Foundation, in Lisbon (Portugal).

At the helm of Altos will be, as of August 1, the American doctor Hal Barron, still president of Research and Development of the pharmaceutical giant GlaxoSmithKline.

Izpisua defends that Altos will combine the virtues of academia (“scientific excellence, freedom and inspiration to address the most challenging problems in biology”) and the best attributes of industry (“focus and speed in a shared mission to transform science in medicines”).

"Our ultimate goal is to find new ways to help all people slow down and even reverse the processes that lead to disease," she says.

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