Rejuvenate old mitochondria
Removal of a single protein rejuvenated aging mice
Sergey Kolenov, Hi-tech+
Scientists have managed to prove that the RNA-binding protein PUM2 is associated with age-related mitochondrial disorders. In addition, they found a way to reverse this process – to rejuvenate individual tissues of experimental elderly mice. The discovery will allow us to develop new methods of combating aging.
Age-related changes are associated with violations of many biochemical mechanisms in tissues and cells. Nevertheless, most of the work on the biology of aging is focused on transcription of matrix RNA – a very important, but far from the only stage of protein production.
Researchers from the Federal Polytechnic School of Lausanne (Switzerland), whose work is described in the press release Targeting an RNA-binding protein to fight aging, went the other way. They studied how aging affects RNA-binding proteins that regulate the work of mRNA after transcription. Scientists have analyzed the cells of old laboratory animals in search of RNA-binding proteins that change with age.
Screening revealed the protein Pumilio2 (PUM2), the expression of which is enhanced in older individuals. It binds to a specific RNA site and blocks the production of the MFF protein.
MFF is considered a key regulator of the reproduction of mitochondria – intracellular power plants. In addition, it is involved in the removal of mitochondria that have failed. The researchers found low concentrations of MFF in the tissues of aging animals. As a result, defective mitochondria accumulated in them, and new ones appeared less frequently.
However, removing PUM2 from aging tissues can completely change the situation. The researchers proved this during an experiment with the calf muscles of mice.
Scientists turned off the PUM2 gene using CRISPR technology and achieved an increase in the concentration of MFF. As a result, normal mitochondrial function was restored in the tissues.
Blocking the production of PUF-8 protein in C.elegans worms led to similar results. Individuals with an edited genome lived longer than their relatives.
Researchers believe that other RNA-binding proteins may also play a role in aging and the development of degenerative diseases. This makes them promising targets for anti-aging therapy.
Article by D'Amico et al. The RNA-Binding Protein PUM2 Impairs Mitochondrial Dynamics and Mitophagy During Aging is published in the journal Molecular Cell – VM.
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