For decades, anti-aging researchers have hit the same frustrating barrier: regardless of the intervention, mouse lifespan extensions stubbornly plateau at around four months when interventions are begun in middle age (about 18 months into a 30-month average lifespan). While this represents modest progress, it falls dramatically short of the transformative results needed to revolutionize human longevity. Now, Dr. Aubrey de Grey’s LEV Foundation is taking direct aim at this long-standing limitation with a radically different approach that could finally shatter what he calls the “four-month glass ceiling.”
“We can get these four months, we could do that 50 years ago. So there’s been zero progress,” says Aubrey de Grey, the foundation’s Chief Science Officer. “This is in dramatic contrast to what’s happened with disease models.”
The LEV Foundation’s strategy represents a fundamental shift in aging research, focusing not on discovering new individual treatments but on the sophisticated engineering challenge of combining existing interventions. This approach—treating aging as an integration problem rather than a discovery problem—could be the key to achieving the dramatic lifespan extensions that have eluded researchers for half a century.
The Limitations of Monotherapy in Aging Research
The traditional approach to anti-aging research has focused primarily on testing individual compounds or interventions—what scientists call “monotherapy.” This approach has yielded treatments that can extend lifespan in mice by about four months, but progress has stalled at this ceiling despite decades of effort.
“Other people understand very well that these combination experiments are very, very important and worth doing, but nobody else is doing them,” de Grey explains. “What are they doing? Well, plenty of people are doing monotherapy. They’re just doing lifespan experiments with individual things.”
This fixation on single-intervention studies creates a critical gap in the field. Researchers continue testing new compounds in isolation, but rarely explore how multiple interventions might work in concert—the very approach that could potentially break through the four-month barrier.
The problem extends beyond merely using single treatments. Many researchers limit themselves to interventions that can be delivered orally through food or water, avoiding the complexities of injections, cell therapies, or gene therapies that might prove more powerful.
“Nobody is doing any combinations of things that involve injections,” de Grey notes with frustration. “Everything is being done with stuff that you can put in the food that could be supplied orally, and this means that you’ve got no cell therapies at all, no gene therapies at all. It makes it basically impossible to break through this four-month glass ceiling that I was speaking about.”
The Engineering Challenge of Biological Integration
The LEV Foundation’s combinatorial approach represents more than just mixing treatments—it acknowledges the fundamental challenge of engineering complex biological systems.
“The damage repair approach is a divide and conquer approach,” de Grey explains. “It [inherently] has two phases, a phase where you develop the components and a phase where you put them together. And that’s true in any branch of engineering, not just medicine.”
Yet unlike mechanical or electrical engineering, biological systems present unique challenges when combining interventions. While engineers can reasonably expect individual components to function together as designed, medicine faces the uncertainty of interactions within incredibly complex living systems.
“In regular engineering, the putting together part is the easy part. You can be pretty sure that if the bits work, then you put them together, it’s going to work,” says de Grey. “Problem with medicine, it’s not like that, because of how pitifully poorly we understand how the body works. If you’re trying to manipulate a system that you have a very poor understanding of, then you’re going to get surprises at that second stage.”
This unpredictability makes the LEV Foundation’s work both groundbreaking and challenging. The team isn’t just stacking treatments—they’re pioneering methods to integrate interventions within biological systems that resist simple mechanical metaphors.
The LEV Foundation’s Experimental Approach
In 2023, the LEV Foundation launched an ambitious experiment involving 1,000 mice that were already 18 months old—roughly equivalent to a 60-year-old human. The scale of this study alone sets it apart from typical aging research.
“We took a bunch of mice, 1,000 mice in fact, a large bunch, that were already 18 months old,” de Grey explains. “These are mice from a strain called black six, which is used in the majority of mouse experiments worldwide and has been for decades. They normally live for about two and a half years on average, so in other words, they had one year to go before their normal time of death when we started.”
In this first experiment, the foundation tested just four interventions simultaneously. The results were promising but still short of their ultimate goal.
“We extended that by about four months. That is pretty much what has already been achieved in the past,” de Grey acknowledges. “Our goal eventually is to beat that by a lot, ideally to treble it, in other words, to give them a 12-month increase in life extension.”
What makes this approach particularly powerful is the foundation’s plan to expand the combination strategy in future studies. “This first attempt, well, we knew it was the first attempt, and we only tried four different things at the same time. Next time we want to try eight,” de Grey states.
Strategic Selection of Interventions
The LEV Foundation isn’t randomly combining treatments. Their selection process follows specific criteria designed to maximize the potential for breakthrough results.
“Individual efficacy is certainly the main one, however there are a few more things,” de Grey explains. “One big thing is that we want them to be as different as possible from each other. Because we definitely don’t want a duplication of effort here, we want to try and find things that are likely to synergize.”
Crucially, the foundation focuses on therapies that work when started in middle age, rather than those that only extend lifespan when begun early in life.
“We’re not interested in things that will extend life if you start when the mice are like six weeks old, but fail to increase lifespan if you start at 18 months,” says de Grey. “We’re interested in appealing to people who are old enough to pay taxes, we’re interested in saving as many lives as possible, so we don’t want to give up on older people.”
This strategic focus on late-life interventions addresses a critical gap in aging research, where many promising therapies only work when started early in life—a limitation that would severely restrict their potential human applications.
The Potential Impact of Breaking the Four-Month Barrier
If the LEV Foundation succeeds in extending mouse lifespan by 12 months instead of just four, the implications would extend far beyond laboratory statistics. De Grey believes this achievement would trigger a fundamental shift in how aging experts communicate with the public.
“If we were to achieve this 12-month extension, then my colleagues would feel that it was safe to start talking about timeframes at last,” he predicts. “Once that happens, I believe my job is done. I can basically retire after that, because there will be an immediate cascade of demands for a proper COVID-scale war on aging.”
This transformation would occur through a cascade effect: scientific experts would influence major public figures, who would then shape public opinion, rapidly creating political pressure for massive investment in aging research.
“The subject matter experts will influence the world’s leading influencers, [including] Joe Rogan and Lex Fridman and Oprah Winfrey the following day,” de Grey explains. “And those people actually have influence, that’s why they’re called influencers. They go out, if they demand something, the general public starts demanding it. And of course the minute the general public starts demanding something, elected representatives who have one goal in life, which is to get re-elected, will go and do it.”
The Road Ahead: Next Steps for Combinatorial Research
The LEV Foundation stands ready to expand its experimental program, with plans already in place for more ambitious combination trials.
“We are totally ready. We know what we want to do. We’ve got all the collaborators and suppliers of reagents and so on lined up. We just need [funding],” de Grey states.
The next phase will double the number of interventions tested simultaneously, from four to eight, potentially creating synergies that could finally break through the stubborn four-month ceiling.
This work represents a transition from what de Grey describes as “phase one” of anti-aging research—developing individual components—to “phase two”—combining those components into comprehensive treatment regimens. After decades focused on developing individual interventions at the Methuselah Foundation and SENS Research Foundation, de Grey is now leveraging those advances to create integrated approaches through the LEV Foundation.
“At SENS Research Foundation, and at Methuselah Foundation before that, I was only doing phase one. I was only working on the bits,” he explains. “Now, however, I’m working specifically on combining the easier bits because the easier bits are the ones that are ready to be combined and the hard ones aren’t.”
As the foundation works toward its ambitious goal of tripling the typical lifespan extension in mice, the implications for human longevity grow increasingly tangible. Breaking the four-month barrier wouldn’t just represent an incremental advance—it would potentially validate the entire engineering-based approach to combating aging, opening the door to treatments that could extend human healthspan by decades rather than years.
In the high-stakes world of aging research, the LEV Foundation’s combinatorial strategy represents not just a new experimental approach, but a fundamental reimagining of how we might finally overcome humanity’s oldest and most universal challenge.
