A lab experiment in yeast reveals a surprising enzyme system that may connect diet, gut microbes and aging more tightly than we thought.
A next-generation cancer drug just pulled off an unexpected trick: it slowed aging. In a new study from Queen Mary University of London, researchers found that the experimental drug rapalink-1 extended the lifespan of yeast by tuning one of the body’s most powerful growth-control systems.
🧬 Even more surprising, the team discovered that a little-known family of enzymes called agmatinases help keep this system balanced. These enzymes depend on metabolites produced by diet and gut microbes, hinting that what we eat may shape longevity at a deeper level than previously understood.
Key Takeaways
- Rapalink-1 extended yeast lifespan by dialing down TOR, a major growth-and-aging pathway.
- Agmatinases formed a hidden metabolic loop that keeps TOR activity in balance.
- Disrupting agmatinases sped up growth but accelerated aging, showing a surprising trade-off.
- Agmatine and putrescine boosted resilience in certain conditions, but effects depend heavily on metabolic context.
- Researchers warn against casual agmatine supplementation, noting possible risks.
What Scientists Found
The research team tested rapalink-1, an advanced drug designed for cancer therapy, in fission yeast, a simple model that reliably predicts many fundamental aging mechanisms.
🍃 The drug slowed cell growth and extended lifespan, echoing what earlier drugs like rapamycin have shown but through a more precise action on TORC1, the growth-promoting side of the TOR pathway.
The TOR pathway acts like a central control tower for nutrient sensing and growth. When TOR runs hot, cells grow quickly but age faster. When TOR is gently dialed down, organisms from yeast to mice tend to live longer.
The Hidden Feedback Loop That Surprised Researchers
💡 Here’s the twist: the team found that enzymes called agmatinases form a previously unknown metabolic feedback loop that regulates TOR activity.
These enzymes convert agmatine into polyamines, small molecules that support cell survival. When the team disabled agmatinases, yeast grew faster but aged rapidly, showing a built-in trade-off between growth and long-term health.
“Agmatinases appear essential for healthy aging. This metabolic layer controlling TOR may be conserved in humans,” said study author Dr. Charalampos Rallis.
Why Diet and Gut Microbes Suddenly Matter More
The most intriguing part: agmatine is made by gut microbes and influenced by diet. That means this enzyme system could be one of the hidden ways nutrition and the microbiome tweak our rate of aging.
🥬 Foods high in arginine, fermented foods, and microbial diversity may all shift agmatine levels, although it’s too early to draw firm recommendations.
The study suggests that nutrition might influence aging partly through this agmatinase–TOR loop.
Why Agmatine Supplements Are Not a Shortcut
🛑 While agmatine supplements exist, the researchers urge caution.
“Agmatine is only helpful when certain metabolic pathways are intact, and in some cases it can worsen health risks,” Rallis noted.
In other words, this is not a DIY longevity hack. The benefits depend heavily on the cell’s metabolic context, which varies widely among individuals.
What This Means for the Future
This work highlights a fresh angle in aging science: pairing TOR-targeting drugs with diet or microbiome strategies.
It also raises new questions:
- Could future anti-aging therapies target agmatinases?
- Can diet or probiotics meaningfully influence this metabolic loop?
- Will rapalink-1, or similar next-gen TOR inhibitors, eventually be tested in mammals for longevity?
For now, the findings deepen our understanding of how growth, metabolism and aging intertwine, and why tweaking one part of the system can ripple across the whole body.
Sources
- Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast
https://doi.org/10.1038/s42003-025-08731-3
