Rapalink-1 May Extend Yeast Lifespan Through the TOR Pathway

Scientists are continuing to investigate how people might live longer while maintaining better health. A noteworthy advance in this area has emerged from experiments involving fission yeast, an organism frequently used in ageing research.

Researchers at Queen Mary University of London have been evaluating a new drug, Rapalink-1. It builds on rapamycin, an established immunosuppressant previously found to extend the life of cells and rodents. In the latest experiments, Rapalink-1 prolonged yeast lifespan to a comparable extent to rapamycin.

Rapalink-1, agmatine and yeast ageing

Molecular analysis also showed that the treatment boosted production of enzymes which transform agmatine-a compound produced by gut bacteria-into several other chemicals.

Earlier research has indicated that agmatine may lengthen the lifespan of the microbes' host. The new tests show that processing this compound can also indirectly influence genes associated with ageing, helping to explain why Rapalink-1 proved effective.

Although the underlying biology is highly technical, the implication is important: it offers researchers a clearer picture of how yeast cells may be enabled to live longer through a mechanism that could also be relevant to human cells.

"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 cellular biologist Charalampos Rallis.

"Because agmatine is produced by diet and gut microbes, this work may help explain how nutrition and the microbiome influence aging."

How Rapalink-1 affects the TOR pathway

Rapalink-1 and rapamycin both act on a biological mechanism known as Target of Rapamycin, or TOR. This pathway is already recognised for its connections to cellular ageing and disease, initially demonstrated in yeast, roundworms, flies and mice. Humans have a comparable pathway as well.

The study also established that Rapalink-1 operates via TORC1, the section of the TOR pathway that governs cell growth. By slowing TORC1 activity, Rapalink-1 causes cells to grow at a reduced rate but survive for longer.

"Understanding how TORC1 activity is tuned may be beneficial in both normal aging and also pathological states as well as in cancer where TOR plays important roles," the researchers write in their paper.

Early-stage implications for healthy ageing

A miraculous longevity pill is not likely to reach the market soon. Nevertheless, these findings improve understanding of ageing as an exceptionally complicated process, in which our bodies progressively deteriorate and lose capacity over time.

This physical decline raises the likelihood of numerous illnesses, including Alzheimer's and arthritis. Ultimately, drugs such as Rapalink-1 could potentially keep some of these conditions at bay for longer. Rapalink-1 is already being tested for its ability to combat cancer tumours and improve transplant outcomes.

The researchers stress, however, that the work remains at an early stage. Agmatine supplements, which are marketed as supporting good health on the basis of earlier studies, should therefore still be treated with caution.

"We should be cautious about consuming agmatine for growth or longevity purposes," says Rallis. "Our data indicates 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 research has been published in Communications Biology.