Nature Aging: Longer lifespans come from faulty RNA processing

RNA is an important information transmitter in our cells and a blueprint
for protein production.
When the newly formed RNA is processed, so-called introns are cut out, producing mature mRNAs
that code for proteins.
This cut is called a "splicing" and is controlled
by a complex called a "splicer".

Long-lived nematodes

"We found a gene called PUF60 in nematodes, which is associated with RNA splicing and regulating lifespan," said
Dr.
Huang Wenke, a Max Planck scientist who discovered the discovery.
Mutations in this gene lead to inaccurate splicing and retention of introns in specific RNAs
.
As a result, this RNA forms a small amount of the corresponding protein
.
Surprisingly, nematodes with mutations in this PUF60 gene significantly longer lived longer than normal nematodes
.

Particularly affected by this defective product are some proteins
that play a role in the mTOR signaling pathway.
This signaling pathway is an important sensor for obtaining food and a control center
for cellular metabolism.
It has long been the focus
of aging research as a target for potential anti-aging drugs.
The researchers also found that in human cell culture, a decrease in the activity level of PUF60 leads to a decrease
in the activity of the mTOR signaling pathway.

Human PUF60 mutation

"We believe that by altering the fate of introns in RNAs, we have discovered a new mechanism for regulating mTOR signals and lifespan," said
Adam Antby director, Max Planck, 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 can be helped
by drugs that control mTOR activity.
Of course, this needs more research
.
”

essay

Decreased spliceosome fidelity and egl-8 intron retention inhibit mTORC1 signaling to promote longevity