A new cancer drug candidate may also slow aging in surprising ways. Researchers at Queen Mary University of London’s School of Biological and Behavioural Sciences have shown that rapalink-1, a next‑generation TOR inhibitor, can extend the chronological lifespan of fission yeast, a widely used model organism for studying fundamental biological processes. In a study published in Communications Biology, Juhi Kumar, Kristal Ng, and Charalampos Rallis demonstrate that both pharmaceutical compounds and naturally occurring metabolites can influence lifespan by acting on the Target of Rapamycin (TOR) pathway.
TOR Pathway: A Central Regulator of Growth and Aging
The TOR pathway is an evolutionarily conserved signaling system present from yeast to humans. It governs cell growth and aging and is intimately connected to major age-related diseases such as cancer and neurodegenerative disorders. Because of its broad influence, TOR has become a focal point in anti-aging and cancer research, with drugs like rapamycin already shown to extend healthy lifespan in multiple animal models.
Rapalink-1, the compound studied here, is a newer TOR inhibitor under investigation for cancer therapy. The researchers observed that rapalink-1 slowed certain growth aspects in yeast while also lengthening their lifespan, an effect that appears to operate primarily through TORC1, the growth-promoting arm of the TOR pathway.
Discovery of a Metabolic Feedback Loop Involving Agmatinases
An unexpected finding revealed a significant role for a family of enzymes called agmatinases, which convert the metabolite agmatine into polyamines. These enzymes seem to participate in a previously unrecognized metabolic feedback loop that helps maintain balanced TOR activity. When agmatinase activity was disrupted, yeast grew faster but showed signs of accelerated aging, highlighting a trade-off between rapid growth and long-term cellular health.
The study also showed that adding agmatine or putrescine (a related compound) supported longevity in yeast and improved growth under certain conditions.
"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," says Dr. Rallis. "Because agmatine is produced by diet and gut microbes, this work could help explain how nutrition and the microbiome influence aging."
Caution on Agmatine Supplementation
Dr. Rallis emphasized cautious interpretation of agmatine supplements currently available on the market: "We should be careful about using agmatine for growth or longevity purposes. Our data indicate that agmatine supplementation can be beneficial for growth only when specific metabolic pathways related to arginine breakdown remain intact. Moreover, agmatine does not universally promote positive effects, as it can contribute to certain pathologies."
Taken together, these findings illuminate important links between TOR signaling, metabolism, and lifespan. They may guide future strategies that combine TOR-targeting drugs with dietary or microbiome‑based approaches to studying healthy aging, cancer biology, and metabolic disease.
