Congratulations to Dr. Karl Riabowol on his new grant!

Prepared by Dr. Karl Riabowol

Age is very strongly linked to the probability of developing nearly all cancer types. Cell aging, also called senescence is largely controlled by stress signals of different types including those generated internally in the cell and by external agents like chemicals and radiation that damage DNA. We have identified a protein we called ING1a that is only found in humans and non-human primates (apes and monkeys), which is induced by stress and very rapidly causes cells to age. We previously found that it does this through a role in the nucleus of cells and now we have discovered another role at the mitochondria that function as the powerhouse of the cell.

In our project we propose to determine exactly how ING1a can so rapidly make cells age via this unique mitochondrial mechanism and we will also determine what causes cells to make this protein normally as human cells age. Our observations in human cells are timely since it was recently discovered in yeast, that both a mechanism operating in the nucleus of yeast cells and a mitochondrial energy-based pathway serve as two distinct major mechanisms to lead to their senescence. This is exciting since it suggests that cell aging may have clear parallels between the yeast that is used as a model organism to study aging, and human cells.

We will use a series of ING1a protein fragments tagged with a molecule that is fluorescent so we can see it in cells under the microscope, to see exactly what piece of ING1a causes cells to age. After that we will determine what other proteins this fragment binds to so we can understand how it causes rapid cell aging. Once we determine the pathway(s) in the cell that are used to make the cell produce ING1a, and the pathways used by ING1a to cause rapid cell aging, we will plan strategies to block ING1a production and/or block its effect in cells to allow cells to grow for longer periods of time. There is good evidence that increasing cell lifespan will improve human healthspan by delaying the onset of many different age-related ailments such as cancer.

This work was funded through CIHR Spring 2021 Project Grant