Researchers have shown that new TOR inhibitor rapalink-1 prolongs lifespan in fission yeast, offering insight into how drugs may slow ageing.
Rapalink-1, a next-generation TOR inhibitor currently under investigation for cancer therapy, slowed cell growth and significantly extended lifespan in yeast models, acting through TORC1 — the growth-promoting arm of the TOR pathway.
The TOR (Target of Rapamycin) pathway is active in both yeast and humans.
It is a central regulator of growth and ageing and plays a major role in age-related diseases including cancer and neurodegeneration. Drugs such as rapamycin have already shown promise in extending healthy lifespan in animals.
The study also revealed a crucial role for enzymes called agmatinases, which break down the metabolite agmatine into compounds known as polyamines. These enzymes are part of a previously unknown “metabolic feedback loop” that regulates TOR activity.
When agmatinase function was lost, cells grew faster but aged prematurely, showing a trade-off between short-term growth and long-term survival. Supplementing yeast with agmatine or putrescine — compounds linked to this pathway — also promoted longevity and improved cell health under certain 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 Charalampos Rallis.
“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 available but urged caution.
He said: “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 research into healthy ageing, cancer biology and metabolic disease, pointing to new strategies that could combine TOR-targeting drugs with dietary or microbial interventions.