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Mice Lived 30% Longer (And Better) on This Drug Combo and Scientists Are Eyeing Human Trials Next

Scientists combine two cancer drugs to delay aging and disease in mice.

Tibi Puiu
May 29, 2025 @ 8:59 pm

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AI-generated illustration. Credit: ZME Science/SORA.

One of the most enduring dreams in medicine is not simply to live longer, but to live better — into old age without the burdens of chronic disease, frailty, or failing organs. Now, researchers may have nudged science a small step closer to that goal.

In a new study out this week, scientists report that a combination of two existing cancer drugs — rapamycin and trametinib — extended the lifespans of mice by as much as 35 percent. More strikingly, the treated animals also aged more gracefully. They stayed healthier longer, with delayed onset of tumors, less inflammation, and signs of better heart and brain function.

“We do not expect a similar extension to human lifespans as we found in mice,” said geneticist Dame Linda Partridge, co-senior author of the study and a professor at University College London and the Max Planck Institute for Biology of Ageing. “But we hope that the drugs we’re investigating could help people to stay healthy and disease-free for longer late in life.”

One plus one equals… more

Combination of rapamycin and trametinib extends mouse lifespan. Credit: K Link/Max Planck Institute for Biology of Aging.

The study began with a simple but powerful question: Could two known “geroprotective” drugs, when combined, be greater than the sum of their parts?

Rapamycin has long been a favorite in longevity science. Originally derived from soil bacteria on Easter Island, it’s widely used to prevent organ rejection in transplant patients and has consistently been shown to extend lifespan in mice, even when given late in life. Trametinib, a drug approved to treat melanoma, is newer to the aging field. Though it had extended lifespan in fruit flies, its effects in mammals were unknown — until now.

To find out, researchers at the Max Planck Institute fed hundreds of mice diets containing rapamycin, trametinib, or a cocktail of both, starting when the animals were six months old (middle-aged, by mouse standards).

The results were eye-opening.

Rapamycin alone extended median lifespan by about 17 to 18 percent. Trametinib by itself added about 7 to 16 percent. But together, the drugs boosted lifespan by 26 to 35 percent — with female mice showing the most dramatic benefit.

Maximum lifespans also rose: up to 32 percent longer in females and 26 percent in males.

The researchers emphasize that this wasn’t just about longer lives — it was about healthier ones. Mice receiving both drugs were more active in old age, had less age-related weight gain, and showed slower declines in heart performance. They even had reduced brain inflammation and lower rates of cancer.

“We found that combining rapamycin and trametinib had additive effects on both lifespan and healthspan,” said lead author Sebastian Grönke. “The combination significantly reduced tumors and inflammation compared to either drug alone.”

How it works — and why it matters

Both drugs target a biological system known as the Ras/Insulin/TOR signaling network. It’s a sort of molecular thermostat that regulates growth and metabolism and has long been implicated in aging and age-related diseases. Rapamycin inhibits mTORC1, a key protein complex in this network, while trametinib blocks MEK proteins further down the Ras pathway.

Together, the drugs appear to hit the system from two sides. And that seems to trigger gene expression changes that neither drug can produce on its own. When researchers analyzed tissue from the treated mice, they found that the combination caused unique shifts in gene activity — particularly in genes involved in inflammation and immune function.

In the brain, for example, older mice normally show increased glucose uptake, which is associated with cognitive decline. But in animals given the drug combo, this age-related change was entirely blocked. Likewise, markers of chronic inflammation fell significantly in the brain, kidney, spleen, and muscle.

The treatment also delayed the appearance of tumors. While nearly 70 percent of untreated male mice had liver tumors by 24 months of age, that number dropped significantly in those receiving both drugs. The combo even suppressed spleen tumors in males — an effect neither drug achieved on its own.

And, importantly, the combination didn’t increase the side effects already associated with either drug. While rapamycin alone caused elevated blood sugar levels, trametinib did not, and the combination did not exacerbate this problem.

From mouse to medicine cabinet?

The leap from mice to humans is enormous, and longevity research has had its share of setbacks. Still, this study stands out because both rapamycin and trametinib are already approved for human use, albeit for different reasons.

That regulatory head start could accelerate the path toward clinical trials, especially as scientists look for ways to repurpose existing medications for new uses. In fact, previous human studies have hinted that rapamycin might have anti-aging effects, such as extending the fertility window in women or improving immune response in older adults.

“Trametinib, especially in combination with rapamycin, is a good candidate to be tested in clinical trials as a geroprotector,” said Grönke. “We hope that our results will be taken up by others and tested in humans.”

Partridge added that the team’s current focus is on optimizing trametinib’s dosing in animal models to balance its benefits with potential side effects. “Further research in humans in years to come will help us to elucidate how these drugs may be useful to people, and who might be able to benefit.”

Cautiously optimistic

For now, these findings offer a compelling new clue in the quest to delay aging. They reinforce a growing scientific view: aging is not just an inevitable decline. It is a biological process that can be studied and potentially slowed through targeted interventions.

The research also supports a broader idea gaining traction in geroscience circles: that combinations of drugs, each acting on different points of the aging pathway, may be more effective than any one treatment alone.

In the end, these mice didn’t just live longer. They lived better. And while humans may not be lining up for longevity cocktails anytime soon, the science behind aging is starting to look a little less like science fiction — and a little more like a future within reach.

The findings appeared in the journal Nature Aging.

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