Two cancer drugs just proved aging isn't inevitable, but death is…
The science that could change aging forever - and the pioneer who didn't live to see it.
As a doctor who has spent years watching patients deteriorate from age-related diseases, and as a neuroscientist fascinated by mechanisms of aging, I’ve learned to temper my excitement about longevity research. Too many promising studies never translate to humans. But when I saw the Nature Aging paper published just days ago, I couldn’t help myself — I read it three times (1).
Researchers used two cancer drugs already sitting in hospital pharmacies — rapamycin and trametinib — to extend mouse lifespans by 30%. That’s the equivalent of a human living to 104 instead of 80. These aren’t experimental compounds that might take decades to reach patients. They’re FDA-approved medications with well-established safety profiles that specialists prescribe daily.
The breakdown fascinated me mechanistically. Rapamycin alone increased lifespan by 15–20%, which is unsurprising given its reputation as a proven geroprotector. Trametinib managed 5–10% independently — remarkable for a drug that wasn’t even known to affect aging in mammals, though fly researchers had whispered about its potential for years.
But together? Something magical happened…
A full 30% extension, suggesting these pathways communicate in ways we’re only beginning to understand.
Both drugs target different nodes of the Ras/Insulin/TOR network. Rapamycin inhibits the mTOR pathway and dramatically increases lifespan in various species, including the research nematode C. elegans (2). FDA-approved in 1999, we use it to prevent organ transplant rejection, treat rare tumors, and coat coronary stents. Trametinib acts on MEK1 and MEK2 proteins, receiving FDA approval in 2013 for treating metastatic melanoma with specific mutations.
Mikhail Blagosklonny’s Story
The hypothesis linking mTOR signaling to aging and cancer was formulated by Mikhail Blagosklonny, a brilliant scientist and longtime editor-in-chief of Aging. I published one of my papers there and met Mikhail at a conference, where he advocated for rapamycin as a means to improve longevity.
Mikhail wasn’t just passionate — he was a true believer who put his money where his mouth was, taking rapamycin himself based on his own research. (This resonates with me personally, as I take norvaline, an amino acid that prevented Alzheimer’s in mice in one of my studies.) His enthusiasm was infectious in the way that only comes from genuine conviction. He could talk for hours about how this billion-year-old cellular mechanism held the key to extending healthy human lifespan, his eyes lighting up as he described the possibilities.
That’s why what happened to Mikhail devastated me. In January 2023, he was diagnosed with lung cancer that had already metastasized to his brain. I found myself compulsively checking his personal blog, watching this giant in aging research confront the very mortality he’d spent his career trying to defeat. His final post, simply titled “my battle with cancer,” was heartbreaking to read — raw, honest, and utterly human. Mikhail died in October 2024 at just 63, far too young for someone who understood aging so deeply.
The irony wasn’t lost on any of us in the field. Here was a man who dedicated his career to understanding and preventing aging, who took the very drugs he researched, yet cancer still claimed him. It’s a sobering reminder that death doesn’t care about our theories or preparations.
Death remains unpredictable, even for those who understand it best…
Beyond Just Living Longer
Mikhail would have been thrilled by this new research because it addresses his core belief: aging isn’t inevitable. The combination therapy didn’t just extend lifespan — it dramatically improved healthspan. The mice showed measurable decreases in inflammatory markers throughout their brains, kidneys, muscles, and spleens.
Chronic inflammation drives age-related diseases. It makes us frail, sick, and cognitively impaired as we age. By suppressing it, this drug combination essentially hits the pause button on biological processes that destroy our bodies over time.
Cancer development was also significantly delayed. The number of liver tumors dropped in both sexes, while spleen tumors were eliminated entirely in male mice. Given that cancer risk increases exponentially with age, any intervention that delays onset while extending lifespan addresses two problems simultaneously. However, always keep Blagosklonny’s case in mind.
The Human Translation
The ERAP clinical trial is already testing rapamycin in Alzheimer’s patients, measuring changes in brain glucose metabolism using PET scans. If results mirror what we’re seeing in mice — reduced brain inflammation and normalized metabolism — we might be looking at the first actual anti-aging therapy.
Having studied Alzheimer’s for years, I know how desperately we need effective interventions. The beauty of repurposing existing drugs is speed. We already know these medications are safe for human use. The question isn’t toxicity — it’s whether their anti-aging effects translate across species.
Of importance, a systematic review published in The Lancet last year examined clinical trials of rapamycin for targeting aging in humans (3). Authors found that rapamycin improves physiological parameters related to aging in healthy individuals and those with aging-related diseases. While no adverse events were reported in healthy individuals, increased infections and higher cholesterol levels were noted in those with aging-related conditions. So, we must be patient in our expectations, and future studies should investigate the long-term effects of rapamycin.
You know, I’ve learned to be skeptical of medical breakthroughs. Most don’t survive the transition from lab to clinic. But this feels different. The biological pathways involved are evolutionarily conserved — what works in mice and worms often works in humans. Moreover, these drugs are already in clinical use, which removes the most significant barrier to translation.
So, we might be witnessing the birth of the first generation of true geroprotectors. If a 70-year-old could maintain the physical and cognitive function of a 50-year-old, everything changes. The economic implications are staggering — age-related diseases consume a substantial portion of healthcare resources.
Mikhail Blagosklonny believed the fountain of youth wasn’t a mystical spring but a carefully orchestrated combination of molecules. His work laid the foundation for discoveries like this one. Though cancer took him before he could see his vision fully realized, his legacy lives on in every study that brings us closer to conquering aging itself.
We’re not there yet. But for the first time, “there” feels like an actual destination rather than a fantasy…
References:
1. Gkioni, L., Nespital, T., Baghdadi, M. et al. The geroprotectors trametinib and rapamycin combine additively to extend mouse healthspan and lifespan. Nat Aging (2025). https://doi.org/10.1038/s43587-025-00876-4
2. Robida-Stubbs, S., Glover-Cutter, K., Lamming, D. W., Mizunuma, M., Narasimhan, S. D., Neumann-Haefelin, E., Sabatini, D. M., & Blackwell, T. K. (2012). TOR signaling and rapamycin influence longevity by regulating SKN-1/Nrf and DAF-16/FoxO. Cell metabolism, 15(5), 713–724. https://doi.org/10.1016/j.cmet.2012.04.007
3. Lee, D. J. W., Hodzic Kuerec, A., & Maier, A. B. (2024). Targeting ageing with rapamycin and its derivatives in humans: a systematic review. The lancet. Healthy longevity, 5(2), e152–e162. https://doi.org/10.1016/S2666-7568(23)00258-1
About the Creator
Baruh Polis
Neuroscientist, poet, and educator—bridging science and art to advance brain health and craft words that stir the soul and spark curiosity.
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