LEV begins experiments aiming to double the lifespan of middle-aged mice

Aubrey de Grey has done a lot to promote the idea that aging and death are solvable problems – that the damage done over time by metabolic processes can be reversed, and that there's a chance the first thousand-year-old human may already have been born.

As a founder of the Methuselah Foundation and the SENS foundation, he's convinced billionaires that anti-aging research can give them the only things they lack: time and youth – and as a consequence he's raised hundreds of millions of dollars toward targeted research. Through decades' worth of patient and eternally optimistic media appearances he's attempted to shift the public consciousness around to the idea that aging and death needn't be viewed as inevitable, just as a series of problems that are in the process of being solved.

Long viewed as a big-talking annoyance by many senescence researchers, he's also a compromised figurehead for the movement in 2023, having been suspended and then fired from the SENS foundation after harassment allegations by two young longevity company founders in 2021, in which one stated de Grey had told her it was her responsibility to sleep with wealthy potential donors to bring money in the door.

The Foundation released a statement in 2022 saying that, while de Grey's conduct "did substantiate instances of poor judgment and boundary-crossing behaviors, Dr. de Grey is not a sexual predator," and hinting that the chief issue was more that he wasn't participating in substance abuse programs mandated by his Fitness for Duty agreement. De Grey, for his part, claims it's a hatchet job, and says SENS was poorly run, moving too slow, and wasn't respecting the intent of its donors in its decision making.

So late last year, he started a new foundation: the Longevity Escape Velocity (LEV) Foundation, entirely under his own control this time. The name refers to de Grey's belief that if science manages to outrun death, one problem at a time, eventually we'll reach an "escape velocity" where it won't ever be able to catch us – at least, not through natural causes.

And this month, the LEV Foundation begins its first research program, targeted at "Robust Mouse Rejuvenation."

As a precursor to any human trials, this program will take four promising anti-aging treatments and apply them in various combinations to a group of middle-aged (18-month-old) mice. These mice can typically expect to live to a mean of 30 months, so their remaining lifespan would be expected to be around 12 months. The LEV team hopes to increase both the mean and average lifespan of these mice by at least 12 months.

Why start with middle-aged mice? Well, de Grey tells Lifespan, "the idea is that this will appeal more directly to people who care, vote, pay taxes, and make donations than if you do early-onset interventions." It'll also shorten the time to the finish line.

The four interventions to be trialed are as follows. First, there's rapamycin, an immunosuppressive drug that's been used to help prevent organ rejection, but which has also been shown to suppress aging-related gut biomarkers in mice, to reduce age-related cognitive decline in mice, and to extend the lifespan of both fruit files and worms as part of combination therapies.

The second is a newly-developed, "conjugated" form of navitoclax, a drug that's known to target and remove senescent "zombie" cells in mouse brains – cells that have stopped dividing, but refuse to die. These zombie cells are a key target for longevity and dementia researchers. The new conjugated formulation, says de Grey, should help target the senolytic effects of navitoclax more precisely.

Third up is mTERT, or mouse telomerase reverse transcriptase. This is a gene therapy that targets the telomeres, the protective, repeating "junk" DNA caps on the ends of each leg of a chromosome. We lose a bit of telomere every time our cells divide, and eventually, after about 50 divisions, the cells simply stop dividing. LEV will be trialing an intranasal delivery method using a cytomegalovirus to get the treatment into the body. In a small trial published in PNAS last May, mTERT was found to extend the median lifespan of mice by an impressive 41.4%.

And finally, there's hematopoietic stem cell transplantation (HSCT), delivering the stem cells in the marrow that produce blood and immune cells. This has been used as a treatment for various cancers, as well as a means to "reboot the immune system" and stave off early MS and treat Crohn's disease, and as a remarkably effective cure for HIV.

De Grey tells Lifespan the LEV team won't be waiting for the results of the first thousand-mouse experiment before embarking on the next, and the next after that.

"People don’t donate to Aubrey de Grey because they want the work they’re supporting to be timid," he says. "this is a rolling research program, and our top priority is, as soon as we get this one kicked off, we’re going to design the next one, and to bring in the money, which is about three million dollars for each round ... I’m hoping that we’ll be able to do subsequent rounds more than once a year – maybe every nine months or so – because we don’t need to wait for the results of the first one to decide how to do the second one. We’re also incorporating masses of information from the community, from literature, and we already have a plenty good list of things that we’d like to try in the next round."

The overall aim of the project is twofold: to identify longevity therapies that'll work in humans, and to produce the kind of spectacular results that'll get longevity research onto the Oprah Winfrey show, preparing the unwashed masses for a world in which only taxes remain constant.

"We still have to convince people that this is worth doing," says de Grey. "And many people are deep-seated defenders of aging. They believe that we shouldn’t or can’t do anything about aging."

Turning 60 this year, de Grey must hear the clock ticking, just as his donors are as they invest bulk cash into the possibility that they might be able to hoard their earthly riches a while longer. This energetic public figure may well not reach the velocity he needs to escape death, but the blossoming field of longevity research certainly makes it seem like we've never been closer to the dream of outrunning the Grim Reaper.

Source: LEV Foundation via Lifespan