Researchers at Queen Mary University of London have found that rapalink-1, an experimental TOR inhibitor being investigated for cancer therapy, extends the lifespan of fission yeast. The study also uncovered a role for agmatinases in regulating the TOR pathway through a metabolic feedback loop, suggesting potential links between diet, gut microbes, and aging.
A team from Queen Mary University of London's School of Biological and Behavioural Sciences used fission yeast as a model to test rapalink-1, a next-generation inhibitor of the Target of Rapamycin (TOR) pathway. In work published in Communications Biology in 2025, the study by Juhi Kumar, Kristal Ng and Charalampos Rallis showed that rapalink-1 slows aspects of yeast cell growth while significantly extending chronological lifespan, acting primarily through TORC1, the growth-promoting arm of the TOR pathway.
The TOR pathway, conserved from yeast to humans, is a central regulator of growth and aging and is implicated in age-related conditions such as cancer and neurodegenerative diseases. Drugs such as rapamycin have previously been shown to extend healthy lifespan in animal and cellular models, making TOR a major focus of anti-aging and cancer research.
The researchers also identified a key role for a class of enzymes known as agmatinases, which convert the metabolite agmatine into the polyamine putrescine and urea, as part of a previously unknown metabolic feedback loop that helps balance TOR activity. When agmatinase function was disrupted in fission yeast, cells grew faster but showed shortened chronological lifespan and signs of premature aging, highlighting a trade-off between rapid growth and long-term survival. Supplementing yeast with agmatine or putrescine promoted longevity and improved cell performance under specific conditions.
"By showing that agmatinases are essential for healthy ageing, we've uncovered a new layer of metabolic control over TOR — one that may be conserved in humans," said Dr. Rallis, according to a statement from Queen Mary University of London. "Because agmatine is produced by diet and gut microbes, this work may help explain how nutrition and the microbiome influence ageing."
Dr. Rallis noted that agmatine supplements are already available but urged caution, saying that their benefits for growth appear to depend on certain arginine breakdown pathways being intact and that agmatine can contribute to some pathologies. The findings suggest that future research on healthy aging, cancer biology and metabolic disease could explore strategies that combine TOR-targeting drugs such as rapalink-1 with dietary or microbiome-based interventions.
