Illustration by Kimberly Carney / Fred Hutch
Dr. Dan Gottschling has spent more than a decade using yeast cells to make key discoveries about the aging process. His research is paving the way toward understanding how a person’s genes and diet influence how well they age, how long they live, and their risk of suffering from cancer and other diseases. Gottschling sat down with Quest to talk about the possibility of finding new ways to ease aging’s effects — and about how studying one of nature’s deepest questions changed his outlook on life.
What made you decide to study aging?
I went to an epidemiology talk and saw a graph of the relationship between age and cancer risk; it was flat until about age 40 and then it went up exponentially. In other words, your chance of getting a nonhereditary cancer before you’re 40 is very small. Then it goes up really fast.
If you’re a man who lives to age 55, you have a 50 percent chance of getting a tumor between then and the end of your life. Women have about a 33 percent chance over that same period. I was about 40 when I went to the talk, so it really caught my attention!
Why is it useful to study aging in yeast cells?
All the consequences of aging, whether it’s cancer or Alzheimer’s disease or drier skin, stem from underlying processes in cells. If we can understand those processes, they can have big implications for understanding the diseases and other things that happen downstream.
Yeast cells are ideal models for this. There are an immense number of research tools available because people have studied yeast for a long time. The cells grow fast. So we started looking for changes in yeast that happen as a function of age.
Photo by Bo Jungmayer / Fred Hutch
Can you walk me through one of your key discoveries?
We knew that mitochondria (the parts of the cell that make energy) malfunction as cells age, and we knew this dysfunction contributes to cell damage. But we didn’t know what caused the malfunction. So we studied it in yeast and found that mitochondria were being affected by another part of the cell called the lysosome. The lysosome is important for removing molecules that are damaged when cells undergo stress, such as aging. It also stores molecules like amino acids, which are essentially building blocks for the cells.
We found that the lysosome’s acidity was changing with age and it wasn’t performing its storage function as well. That was disturbing the mitochondria’s ability to function. That research shows how we’re defining this cascade of events that makes cells genetically unstable, something we know can lead to cancer. My gut tells me there’s a similar connection in people.
What’s your next step?
We need to integrate genetic and environmental factors to help us see how cell aging is affected by what you eat, what environment you’re in and who your parents are.
A lot of people think genes are the main key, and there are projects to sequence the genomes of octogenarians and centenarians to see what’s different about them. I’m not so confident they’ll uncover a single answer. The interplay and connections between cells and tissues is very complex, and all of them are influenced by genetics and the environment. The complexity is enormous. Just knowing that someone has gene A or B compared to someone else might not tell us much. We need to understand how all the different factors work together.
Is it overwhelming to face such a complicated problem?
No— it’s exactly why I became a scientist. We’re learning that many things can’t be fixed by a simple pill, even though that’s often what we want. I believe our thinking has been too simple. Curing a disease is akin to illuminating an entire neighborhood. You don’t just show up with a light bulb and have the whole neighborhood awash in light. You first have to put in all the wires and make sure the bulbs are screwed in properly.
Basic scientific research like mine helps us understand all those connections and how they work together — how the system is built, and what the effects are when you tweak the material that goes into it. Maybe in the future someone will be able to put all that information together and identify how to manipulate these different factors to improve our health. I would love to know the answers, but I’m also old enough to understand that I may not see them myself. But someone will, someday, and it’s exciting to move them closer.
Does coming face to face with these weighty questions change how you see the world?
I think about aging a lot for my work, and that’s made me think about it a lot more in general, especially now that I’m in my 50s. Some people become incredibly afraid of death as they get older. But it doesn’t bother me as much as it used to — I’ve come to accept that it’s part of the continuum. It’s gotten hard for me to separate the science of getting older from getting older myself.
Do some people’s cells simply age better?
Yes. We’re all different and it comes come back to this combination of genetics and environment. I can tell you about my father and father-in-law. They were born within a month of each other. My dad still bowls five days a week and is very active. My father-in-law is bedridden, unfortunately. Everyone wants to understand what accounts for this difference — it’s the big question. I really think our little yeast will help us answer it.
How will understanding aging lead to better health?
We can prolong life in yeast cells by changing their genes or changing what we feed them. The hope is that we’ll eventually be able to modulate aging’s effects in people too, either with food or other lifestyle changes, with drugs, or even by genetically altering certain tissues.
In an ideal world, we’d learn how to make the aging process less of a slow decline and more of a square function — you’ll be healthy and feel good, and then all your systems will go down at once. I think that’s the best fate we can hope for.