It may also lead to better treatment of a rare disease that causes rapid aging and pre-mature death of children. “Absolutely heartbreaking” is how Eskiw describes the ravages of Hutchinson-Gilford progeria syndrome (HGPS).
An assistant professor with the Department of Food and Bioproduct Sciences in the University of Saskatchewan’s (Usask) College of Agriculture and Bioresources, Eskiw is the co-recipient of a Canadian Institutes of Health Research (CIHR) award given this summer. The first CIHR award to the college, it is shared with Drs. Troy Harkness (PhD) and Terra Arnason of the USask College of Medicine.
The project is notable for the way it combines Eskiw’s expertise in nutrigenomics (the study of how diet interacts with genetic material) with Harkness and Arnason’s expertise in the connection between cellular aging and metabolism. Their proposal was ranked second among 54 grant applications, and was one of only three awarded in Saskatchewan.
The project grant of $872,000 over the next five years will enable them to determine the role in the aging process of an essential piece of cellular machinery called the Anaphase Promoting Complex (APC).
Aging is the prime focus of Eskiw’s work, and it’s also inextricably linked to his research passion, the functioning of human genetic material. Accustomed to using mice and human cells in the lab, he first thought of working with yeast after chatting with Harkness and Arnason, who use it in their research.
Eskiw came to Harkness with a question regarding a genetic mutation that causes HGPS. It leads to the accumulation of a single toxic protein (called progerin) that accelerates the aging process. “My crazy idea was to take that human gene and protein and put it in yeast to see what would happen,” Eskiw explains. Because yeast ages rapidly, it’s well suited for the study of premature aging.
“The more we talked about it, the more we found overlap in our research. It’s merging,” Eskiw says.
The APC rids cells of ‘junk’ such as old damaged proteins that interfere with proper cell functioning, he explains. He compares it to regular oil changes in a car engine. Previous research from the Harkness and Arnason labs has shown that in both yeast and human cells the APC activity falls off during aging. However, Harkness has identified a series of molecules that reactivates the APC.
In his own research Eskiw has been able to quintuple the lifespan of cells in culture, partly through nutrient deprivation. He explains that when cells don’t take in enough glucose and amino acids, they recycle their ‘junk’ to produce the energy and essential protein they need.
In one of their research models, the team will put the progerin protein inside the yeast cells and treat them with the APC activators “to see if they’ll chew up the progerin protein,” Eskiw explains. He adds “even a moderate effect here will improve the lives of (children with HGPS.)” The disease is incurable so far, and existing treatments produce numerous side effects while only extending the children’s lives by a year or two. They generally die around age 14 from stroke or heart attack.
Eskiw hopes the team’s research also “will have significant impacts in understanding the aging process” in general as well as leading to new strategies to combat it, since the accumulation of proteins such as progerin are implicated during the normal aging process too.
Eskiw says he has always been impressed with the willingness of diverse groups across USask to collaborate and share resources. His roots on campus are actually in the College of Medicine. In 2000 he graduated with a M.Sc. from its Department of Anatomy and Cell Biology (as it was then known). After obtaining his PhD in Cell Biology at the University of Toronto (2004), and working in the UK for nine years, he joined the USask College of Agriculture and Bioresources in 2013.
There, he considers part of his role to “bridge the silos between the colleges.” Moreover, within the college itself, he says he has gained appreciation for his colleagues’ work in developing food products that will benefit both consumers and producers. The focus he brings to the table is “how do specific dietary compounds promote genome functions leading to healthier aging?”
Meanwhile, in better understanding the APC it may be possible to prevent or undo damage in a person as the years tick by.