Targeting this protein could help combat aging
12 January, 2019
Scientists have discovered an unknown genetic mechanism of cell metabolism that becomes increasingly dysfunctional with aging.
Researchers at the École Polytechnique Fédérale de Lausanne (EPFL) in Switzerland suggest that their findings could lead to new targets for treatments to combat aging and age-related conditions.
Their discovery concerns a protein that alters the function of mitochondria, which are the tiny power units inside cells that give them their energy.
The EPFL team found that brain and muscle tissue from aged animals had high levels of the protein, which is called pumilio RNA binding family member 2 (PUM2).
A study paper in the journal Molecular Cell describes how aging induces higher levels of PUM2, which, in turn, reduce levels of another protein called mitochondrial fission factor (MFF).
MFF helps cells break large mitochondria into smaller units and clear them away. The tissue samples from the aged animals also had lower levels of MFF.
The researchers suggest that as animals age, the PUM2/MFF pathway becomes more and more dysregulated.
As PUM2 levels rise, they bring down levels of MFF. The result is that cells become increasingly unable to break up and clear away smaller mitochondria. As time goes by, cells and tissues accumulate more and more large, unhealthy mitochondria.
RNA-binding proteins and aging
PUM2 is an RNA-binding protein. These molecules alter gene expression by binding to the messenger RNA (mRNA) molecules that carry DNA code for cells to process.
In the recent study, the team discovered that when PUM2 binds to mRNA molecules that carry the DNA code for MFF, it blocks cells' ability to make MFF protein from those mRNA molecules.
Most research on the molecules that influence aging in cells and tissues tends to focus on gene transcription into mRNA. However, this is just the first step in the complex process of transferring information held in genes into the workings of cells.
The EPFL researchers discovered the PUM2/MFF pathway when they decided to investigate the step that occurs after gene transcription.
When they screened animal cells to identify RNA-binding proteins that changed with age, they found that PUM2 was particularly elevated in older animals.
PUM2 binds only to mRNA molecules that have sites that it recognizes. When it attaches to the mRNA, it stops the translation of the code into the corresponding protein.
By employing a "systems genetics" approach, the team discovered a previously unknown mRNA that PUM2 binds to. This was the mRNA that carries the code for cells to make MFF.