Annual Report 2013

DRS. ADAM HUGHES, LEFT, AND DAN GOTTSCHLING USED A NEW APPROACH TO RESEARCHING CELLULAR BIOLOGY - AND MADE AN IMPORTANT FINDING IN AGING RESEARCH.

DRS. ADAM HUGHES, LEFT, AND DAN GOTTSCHLING USED A NEW APPROACH TO RESEARCHING CELLULAR BIOLOGY - AND MADE AN IMPORTANT FINDING IN AGING RESEARCH. Photo by Matt Hagen

Researchers start at beginning, discover genesis of aging

After a decade of closely examining yeast cells, last year Dr. Dan Gottschling published one of the most important recent discoveries in the field of aging research.

But the breakthrough was only possible thanks to development of new technology, a willingness to cast aside old assumptions, a long-term commitment from philanthropic supporters and a talented postdoc with a "nose for research."

Last year, Gottschling and Dr. Adam Hughes published their finding that links the onset of the aging process in simple brewer's yeast – the model system that Gottschling and others use to provide clues to human diseases – to a metabolic change in the microscopic sacs in cells that store nutrients. The pair used special screening technology developed by Gottschling to determine that when acidity levels dropped in cell components known as vacuoles, another vital component of cells called mitochondria – the source of energy within cells – began to deteriorate. These were essentially the first dominos to fall in the process of aging, a phenomenon Gottschling is studying to unearth the mechanisms underlying age-related diseases such as cancer and some degenerative conditions.

It was a significant finding for Gottschling and for Hughes, who was attracted to Fred Hutchinson Cancer Research Center four years ago specifically to work with Gottschling.

Like so many discoveries in basic sciences, the findings required years of research. But one key event that made it all possible was the scientists' decision to cast aside a long-held assumption in aging research: that mitochondria deteriorate over time due to their chemical reaction with molecules containing oxygen.

"We eschewed this idea and decided to let the cells tell us what was going on," Gottschling said. "As a geneticist, this meant doing experiments in an unbiased manner. This is what led us to the discovery of the role of the vacuole in causing the mitochondrial defect with age in yeast." This approach, and developing new technology to measure changes in the cell, allowed the two scientists to make their discovery.

Gottschling believes basic sciences research, which yields many insights for treatment advances, can thrive only in an environment like Fred Hutch, where its value is understood and supporters invest in it over the long-term. But the breakthrough was also made possible thanks to scientific talent, and Gottschling credits Hughes for taking a fresh approach to the research and for painstakingly studying and analyzing results.

Taking their discovery a step further, the two scientists were able to extend the life of yeast cells and maintain ideal acidity levels within vacuoles by reducing their nutrient intake. This observation may help explain why some species, including mammals, live longer when calorie levels are restricted.

The discovery's clinical potential lies within monitoring the process on a grander scale, which could help scientists gauge where patients are in the aging process, and how diseases like dementia and cancer develop.

"There is still plenty of room for more discovery," Gottschling said.

Fred Hutch’s Basic Sciences Endowment – which provides a reliable source of funding for fundamental research like Gottschling’s – was established in 2011 through a generous anonymous estate gift and has been supported by numerous benefactors, including Karl and Carol Ege.

DAN GOTTSCHLING OF THE BASIC SCIENCES DIVISION
Photo by Matt Hagen
“We eschewed this idea and decided to let the cells tell us what was going on.”

– Dr. Dan Gottschling


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