Study examines longer life through defective RNA processing

Researchers at the Max Planck Institute for Biology of Aging in Cologne have now discovered that the control of RNA metabolism is crucial for regulating the longevity of animals. They found that worms live longer when certain RNAs are processed differently during RNA maturation. This could be an additional way for organisms to control the aging process.

RNA is an important transmitter of information in our cells and serves as the blueprint for the production of proteins. When freshly formed RNA is processed, so-called introns are excised to produce the mature mRNA coding for protein. This cutting is called “splicing” and is controlled by a complex called the “splicesome”.

Long-lived worms

“We found a gene called PUF60 in worms that is involved in RNA splicing and regulates lifespan,” says Max Planck scientist Dr. Wenming Huang, who made the discovery. Mutations in this gene caused inaccurate splicing and retention of introns within specific RNAs. Consequently, lower amounts of the corresponding proteins were formed from this RNA. Surprisingly, worms with this mutation in the PUF60 gene lived significantly longer than normal worms.

Some proteins that play a role in the mTOR signaling pathway were particularly affected by this faulty production. This signaling pathway is an important sensor for the availability of food and serves as the control center for cell metabolism. As a target of potential antiaging drugs, it has long been the focus of aging research. The researchers were also able to show in human cell cultures that reduced PUF60 activity leads to reduced activity in the mTOR signaling pathway.

PUF60 mutation in humans

“We believe 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 published in aging in nature.

“Interestingly, there are also human patients with similar mutations in the PUF60 gene. These patients have growth and neurodevelopmental disorders. Perhaps these patients could be helped in the future by administering drugs that control mTOR activity. But of course more research is needed.”