Researchers have discovered a mutation that significantly increases lifespan

RNA Biotechnology
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RNA Biotechnology

Scientists have found that if introns remain in certain RNAs, worms live longer.

A study found that faulty RNA processing could result in a longer lifespan.

Max Planck scientist Dr. Wenming Huang who made the discovery.

This gene’s mutations resulted in inaccurate splicing and the retention of introns within certain RNAs. As a result, less of the corresponding proteins were produced from this RNA. Surprisingly, worms with the PUF60 gene mutation survived significantly longer than normal worms.

The Roundworm Caenorhabditis elegans Longevity Gene

The roundworm Caenorhabditis elegans is an important model organism in aging research. The worm in the image is labeled with GFP::RNP-6. Credit: Max Planck Institute for Biology of Ageing

Particularly affected by this defective production were some proteins that play a role in the mTOR signalling pathway. This signalling pathway is an important sensor for the availability of food and serves as a control centre of cell metabolism. It has long been the focus of ageing research as a target of potential anti-ageing drugs. The researchers were also able to show in human cell cultures that reduced levels of PUF60 activity led to lower activity of the mTOR signalling pathway.

PUF60 mutation in humans

“We think that by altering the fate of introns in RNAs, we have discovered a novel mechanism that regulates mTOR signaling and longevity,” says Max Planck Director Adam Antebi who led the study. “Interestingly, there are also human patients with similar mutations in the PUF60 gene. These patients have growth defects and neurodevelopmental disorders. Perhaps in the future, these patients could be helped by administering drugs that control mTOR activity. But of course, this needs more research.”

Reference: “Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity” by Wenming Huang, Chun Kew, Stephanie de Alcantara Fernandes, Anna Löhrke, Lynn Han, Constantinos Demetriades and Adam Antebi, 19 September 2022, Nature Aging
DOI: 10.1038/s43587-022-00275-z

The study was funded by the Max Planck Society.

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