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Leah Olson

What do fish brains, weight loss, and the maximum human lifespan have in common? Leah Olson, biology faculty member since 1987, explains.

Reprinted from the September 2007 issue of the Alumnae/i Community Update eNewsletter

You just finished the third year of the Summer Science Program at SLC, where students and faculty members work together on an ongoing research project. What are you studying?

I’m looking at the energy decisions of two species of blennies—small fish that live in holes in coral reefs. My project grew out of Ray Clarke’s study of the habitat choices of these fish. The species are very similar and eat much the same food, but one lives at the bottom of the reef and the other lives higher up. Through a series of experiments Ray found that both species would rather live in the top part of the reef, because there’s more food there. But one species is much more aggressive than the other and will fight for—and win—the more desirable spot. The aggressive species has a much higher metabolism, so it needs almost twice as much food as the other fish. It couldn’t survive if it lived on the bottom of the reef. Because it has a higher metabolism, it also has more energy for fighting.

You teach classes like Pschyoneuroimmunology and The Biology of Living and Dying—what does that have to do with fish habitats?

These blennies, like humans, have a hormone called leptin. When leptin was discovered in 1994, people called it the “fat hormone,” because it is produced in fat cells. It tells the brain how much fat you have, and controls whether you feel hungry or full.

Can altering your leptin levels make you lose weight?

That’s what people thought at first. They did experiments on mice that were genetically modified to be obese. The mice were so fat they could barely waddle to their food bowls, but when they received leptin injections their weight quickly returned to normal. Unfortunately, this doesn’t work in humans, except for the very few whose obesity is caused by a genetic abnormality that affects leptin production.

Sounds like a dead end.

Not at all—these experiments opened up our understanding of metabolism and regulation systems in the brain. Leptin, it turns out, controls not just whether you feel hungry, but your overall metabolism, telling it whether to speed up or slow down to deal with the amount of food you’re consuming.

…Which is related to reef ecology?

Yes. Leptin can influence what ecologists call “life history traits”— where to live, when to reproduce, how many offspring to bear, and how long to live. These are all energy decisions, and leptin is a major player in them. What’s going on between the two species of blennies is a difference in their energy decisions. My project is looking at the leptin system in the blennies to find a physiological explanation for their behavior.

How are the students involved in the research?

They’re directly involved with the process of discovery. To answer these huge questions about energy decisions and how they affect habitat choices on the reef, we are creating a detailed brain atlas of the two species. The students take slices of the fishes’ brains, stain them, and examine them under a microscope to see which parts of the brain respond to leptin. It’s an incredible lesson in neuroanatomy for them. And it’s a brand-new area of research—no one has looked at these fishes’ brains before.

What do you hope to find?

That there might be differences between the number of leptin receptors in the two species.

In your class on aging, you teach that aging and eating are closely related. What’s the connection?

Insulin is the hormone that is released when you eat carbohydrates; it allows glucose to be taken up into your cells. Insulin and leptin are very closely related. It turns out that insulin, which is released when you eat, is also key to the process of aging. To put it very simply, it looks like when you stimulate insulin, you stimulate aging.

Do you think science can extend the human lifespan?

Even though modern medicine has made people stay healthier longer and live longer, the actual lifespan of humans hasn’t changed—no one can live past 120. But recently scientists have proven that caloric restriction can make an organism live longer. In experiments, yeast and mice that consume very few calories live up to 50% longer than their normal projected lifespan, and primates on caloric restriction seem much younger and more vigorous than their normally fed peers. Also, there was an experiment in which they fed mice huge quantities of resveratrol, a chemical found in red wine, and they lived much longer.

So we shouldn’t eat much but should drink a lot of red wine?

That’s one way of looking at it. But you’d have to drink something like 100 liters a day to achieve that effect. The goal is to be able to manipulate these biochemical processes without massive quantities of resveratrol.

How does caloric restriction work?

It creates a hostile environment for the body. The body can’t get enough food, so it puts everything on hold, including aging, in the hopes that it will survive this bad period and then reproduce when conditions improve. Anything that stresses you in that way—exercise, for example—can help you live longer, though of course exercise isn’t nearly as extreme, or effective, as caloric restriction.

What happens if researchers unlock the secrets of aging, and we’re able to make everyone live for 140 years?

The social implications of longevity work are complex. A lot of people think this kind or research is suspect because of its potential effect on society. But the people who study longevity are interested not so much in the practical applications but in the intellectual puzzle of it—aging is an intriguing and elusive issue, and we want to understand how it works. Extending the lifespan isn’t the goal of my research. It seems selfish to do this work with the goal of making everyone live longer, without taking into account the long-term implications of increased longevity—which I’m not sure are desirable.

So other than caloric restriction, are there any weight-loss plans that work?

Your metabolism works hard to keep your weight at a set point. The only way to lose weight permanently is to change that set point. There is some research that shows that if you diet for a long time, or if you exercise a lot, your set point can change, and then it won’t be so hard to stay at your desired weight. But it’s not easy to do.

What do you make of the “obesity epidemic”?

The obesity epidemic has changed the way people think about these things. We’re in an environment where there is so much high-sugar, high-fat food available, it has disrupted our ability to regulate our weight. The environment is inducing obesity, because our bodies can’t withstand the temptation of having so much rich food available.

Do you think about your own leptin levels when you step on the scale?

I think about how my body has its own autonomous systems that take care of these things without any deliberate effort on my part. The power of these unconscious systems amazes me. Some people are biologically programmed to never feel full. It’s really hard to overcome that. How do you get conscious control of an autonomous and very powerful system?

Good question. Any advice for losing weight?

I’m not really involved in thinking about practical applications of this research—I’m more concerned with the intrinsic problem-solving aspects. But I can tell you a couple of things: Exercise reduces your appetite as well as burning calories, and feeds into longevity pathways too. Low-carb diets seem to make sense from a biochemical point of view—more so than low-fat diets. Your body is better at regulating fat than carbohydrates. Finally, stay away from fast food!

What do you do when you’re not thinking about leptin?

I garden. I grow a lot of flowers—some vegetables, but mostly the flowers tend to take over.

Do you look at your garden with a scientist’s eye?

The part I like best is in the early spring when the perennials come up, watching the way they unfold. The whole program for the plant’s life is right there. It’s mechanistic, but still very beautiful. I have an aesthetic appreciation of the process—just as I do for the processes of life, growth, and aging in the body.

Olson