A Spanish project in the million-euro competition to extend quality of life: "There are no magic drugs."

Humanity continues to push the limits of longevity . In the last century, life expectancy has skyrocketed, and although this radical life extension—three more years added every decade—appears to be slowing down, the scientific community remains committed to finding ways to defeat aging . The goal: to turn back the biological clock and, consequently, also the chronological clock, which currently sits at over 80 years in Western countries. Meanwhile, the big question still hangs in the air: How much longer can human beings live? Where is the ceiling ?

Research to delay aging is generating increasing interest in the scientific community and has also attracted the attention of major private investors. The most paradigmatic example is the American company Altos Lab , funded by billionaires such as Jeff Bezos: the company has recruited some of the world's leading experts in rejuvenation with the aim of promoting technologies that allow us to live longer and healthier. But this is not the only case of private initiative focused on the challenge of extending life expectancy. The XPRIZE Healthspan competition , run by the American XPrize Foundation, for example, also seeks promising projects in the field of healthy aging, says Rafael de la Torre, coordinator of the Integrated Pharmacology and Systems Neuroscience Group at the Hospital del Mar Research Institute: "Our life expectancy has increased dramatically. The big question here is what quality of life we ​​have at the end." "And the Ministry of Health would surely look upon it sympathetically," he adds, "but I wouldn't put a penny into it. There's a group of people with a lot of money, the XPrize Foundation, who are dedicated to funding what they care about. And one of their challenges is how to ensure that aging has an associated quality of life."

De la Torre (Barcelona, ​​68) has firsthand knowledge of this initiative, a kind of international competition with hundreds of applications and a single winner, whose research is promised to be funded with one million euros for each additional year of quality of life they provide. The scientist leads a project from the Hospital del Mar Research Institute, the Center for Genomic Regulation (CRG), and IrsiCaixa, which has finished among the 40 semifinalists in the competition: only four Europeans have reached this round, and his is the only Spanish one. Now, they have a year ahead of them to demonstrate the initial favorable results of their hypothesis, says the scientist, fully committed to the ultimate goal. “If you have to reach 99 with a very poor quality of life, you'll be damned if you want to reach that age. Quality of life is more important than living two or three more years,” he argues.

As semifinalists, the competition organizers have given them €250,000 to advance their research. “The challenge they [the competition's promoters] are concerned about is how to ensure that aging has an associated quality of life. They're not so much interested in you living to 100, but rather in ensuring that if you reach 90, you get there in the best possible shape,” explains the Catalan researcher. To evaluate the initiatives, the organizers consider whether the projects improve immunological, muscular, and cognitive parameters. They also have an algorithm that measures, based on these results, how many additional years of quality of life this strategy can provide to a person, says De la Torre.

His project combines a three-pronged approach, using two existing molecules—lamivudine and epigallocatechin gallate (EGCG)—and a multimodal intervention based on healthy lifestyle habits. "We're seeking to extend biological age because, ultimately, that's what being younger is all about," the scientist summarizes.

From his office at the Barcelona Biomedical Research Park, De la Torre says that lamivudine was one of the first antiretrovirals used, but in experiments conducted by CRG researchers, it was also shown to be capable of improving cognitive performance in people with Down syndrome. And now its potential is being tested in the early stages of cognitive decline in Alzheimer's. "This old, off-patent drug, which had originally served as an antiretroviral, improves people's cognition," the scientist asserts.

The other leg of his project is a molecule, EGCG, present in green tea. “We had already worked with it and saw that it improved cognitive performance in Down syndrome. We then gave it to people with subjective cognitive decline, which is a preclinical stage of dementia, and in combination with a multimodal intervention (changing diet, physical activity), we saw that cognition improved,” the scientist notes.

Both molecules, De la Torre adds, are "good for cognition," but the mechanisms behind this effect are independent, he says. And that may be somewhat in their favor, according to his hypothesis: "If you mix them, you'd expect synergistic effects, and that has two advantages: you enhance the effect, and if you enhance the effect, you can lower the dose. So, they're two very safe drugs, but if you lower the dose even further, you don't expect anything to happen, just the cognitive effects."

What they also know from their studies on subjective cognitive decline is that one of these molecules also improves fitness : "That is, you're fitter, you have more muscle mass. People with Alzheimer's lose muscle mass and compensate with fat. If you get a treatment that maintains your muscle mass, that's very important. And that's what the ECGC does."

However, all they know about these two molecules is their separate effects, so they will have to start by studying their interaction in mice. If they achieve the favorable results they hope for and win the competition, they will be able to test them in humans. "What we do know is that the effects of EGCG persist for at least a year without taking it. Therefore, it is foreseeable that the combination of these substances will have a beneficial effect on people's quality of life," the scientist predicts.

The third major aspect of his research is an intervention to promote healthy lifestyle habits. An essential strategy, according to the Catalan researcher. “The combination of the two drugs is a bomb. And if it works, it's great because it's also a cheap bomb. But all in all, taking these drugs, if you don't make lifestyle changes, is a waste of time. There are no magic bullets,” he warns. He adds: “These drugs can help precisely, if you change your lifestyle, to have a boosting effect that intensifies and prolongs the effects.”

While waiting for this project or others to shed light on the path to healthy aging, science is also debating whether the longevity revolution has peaked or whether, perhaps, the current generations of young adults will be the first to live less than their parents . Precisely because of this change in lifestyle habits—worse diet, more sedentary lifestyle—that is jeopardizing the health of Western society. De la Torre is clear: “You are going to live longer than your parents. The problem is their quality of life. Your parents, in the end, didn't live so badly. Now, as we have more complications, we end up worse off. Later, but worse.”