A TOR-targeting cancer drug unexpectedly extends yeast lifespan through a newly discovered metabolic feedback loop.
Researchers at Queen Mary University of London’s School of Biological and Behavioural Sciences have found that the new TOR inhibitor rapalink-1 can extend the chronological lifespan of simple fission yeast, which they used as a model organism.
The study, published in the journal Communications Biology by Juhi Kumar, Kristal Ng, and Charalampos Rallis, explores how both pharmaceuticals and naturally occurring metabolites can shape lifespan through the Target of Rapamycin (TOR) pathway.
TOR is a conserved signalling system active in organisms ranging from yeast to humans. It plays a key role in regulating growth and ageing and is closely connected to conditions linked to age, including cancer and neurodegeneration. Because of this, TOR remains a major focus of ageing and cancer research, and drugs such as rapamycin have shown encouraging results in supporting healthy lifespan in animal studies.
Rapalink-1 Extends Lifespan Through TORC1
Rapalink-1, the drug examined in the study, is an advanced TOR inhibitor that is also being evaluated for its potential use in cancer treatment. The team discovered that rapalink-1 not only reduced certain aspects of yeast cell growth but also produced a notable increase in lifespan by acting through TORC1 — the growth-promoting arm of the TOR pathway.
The researchers were surprised to uncover an important role for a group of enzymes known as agmatinases, which convert the metabolite agmatine into polyamines. They found that these enzymes participate in a previously unrecognized “metabolic feedback loop” that helps regulate TOR activity.
When agmatinase activity was disrupted, cells multiplied more rapidly but showed signs of early ageing — highlighting a trade-off between short-term gains and long-term cell health. Providing yeast with agmatine or putrescine, metabolites associated with this pathway, also supported longer lifespan and improved cell performance under specific conditions.
Implications for Human Aging and Nutrition
“By showing that agmatinases are essential for healthy aging, we’ve uncovered a new layer of metabolic control over TOR — one that may be conserved in humans,” said Dr. Rallis. “Because agmatine is produced by diet and gut microbes, this work may help explain how nutrition and the microbiome influence aging.”
Rallis acknowledges that agmatine supplements are available in the market, but stresses: “We should be cautious about consuming agmatine for growth or longevity purposes. Our data indicate the agmatine supplementation can be beneficial for growth only when certain metabolic pathways related to arginine breakdown are intact. In addition, agmatine does not always promote beneficial effects as it can contribute to certain pathologies.”
The findings have broad implications for healthy aging research, cancer biology, and metabolic disease, pointing to new strategies that combine TOR-targeting drugs with dietary or microbial interventions.
Reference: “Rapalink-1 reveals TOR-dependent genes and an agmatinergic axis-based metabolic feedback regulating TOR activity and lifespan in fission yeast” by Juhi Kumar, Kristal Ng and Charalampos Rallis, 29 September 2025, Communications Biology.
DOI: 10.1038/s42003-025-08731-3
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