A conversation with... Dr. Felipe Sierra

April 1, 2010
Dr. Felipe Sierra

Dr. Felipe Sierra, Director of the NIA’s Division of Aging Biology since 2006, recently sat down with NIA writer Megan Homer to talk about the division and exciting prospects in aging research.

Can you tell me a little bit about the NIA’s Division of Aging Biology? What are its main areas of interest, and how is it different from other areas of the NIA’s extramural research program?

The NIA’s extramural research program has four divisions and of those four, the Division of Aging Biology (DAB) is interested in the cellular and molecular mechanisms of aging rather than the mechanisms of disease. We see the diseases as a consequence of what we study and look at the mechanisms that drive the process.

The DAB has three branches. The Genetics and Cell Biology Branch, directed by Dr. Anna McCormick, supports the most basic research—genetics, metabolism, those areas. At the tissue level is the Aging Physiology Branch, led by Dr. Rebecca Fuldner. In that branch, we look at how those molecular and cellular components studied in the Genetics and Cell Biology Branch translate into tissue function and the dysfunction of disease—that’s where we touch into disease. The relatively new Biological Resources Branch, led by Dr. Nancy Nadon, is responsible for studying animal models and developing new ones. This branch also is responsible for a research area that’s becoming quite important right now, comparative biology. This research asks why two relatively similar animals—for example, the mouse and the naked mole rat—have a 30-fold difference in life span and in health. Comparative biology looks at why one species is so successful compared to another. It’s something that we are putting a lot of effort into.

What is your background? What attracted you to aging research?

I’m from Chile. I studied biochemistry at the Universidad de Chile and graduated in 1977. Then I came to the States to do my Ph.D. at the University of Florida [in Gainesville], where I focused on gene expression, specifically human histone genes. After graduating, I went to Switzerland for a postdoc at the University of Geneva, still studying mechanisms of gene expression. I learned that Nestlé was looking for someone to study aging at the molecular level, and that is how I got into the field. It wasn’t a decision, really. It was just something that happened.

That leads me to advice I have for young investigators. You don’t have to have a preconceived idea about what you want to do, especially if you are interested in many things. You will become interested in whatever area you find yourself. I became interested in aging because of my first job. Things eventually ended at Nestlé, so I returned to the United States and a position at the Medical College of Pennsylvania. After going back to Chile for 4 years, while maintaining my lab in Philadelphia, I came to the NIH in 2002.

How have you seen the world of aging biology change in recent years?

Over the years, the quality of the science has increased exponentially. Today, basic aging research is well respected and published in prestigious journals like Science, Nature, and Cell, which did not happen when I entered this field. When I started my career, we were still doing primarily descriptive work. That’s what I did as a researcher—I took young rats and old rats and looked for differences, for changes. We have passed that stage. While there is still descriptive work to be done, we’re now much more into mechanisms.

One of the major advancements for aging biology came out of our office at the NIA in the early 1990s. The Longevity Assurance Gene initiative, spearheaded by Dr. Anna McCormick, changed how our field is viewed in the research community. NIA-supported researchers discovered that genetic components related to longevity could be identified and studied at the molecular level. After that, aging could no longer be perceived by scientists as something that “just happens.”

We have also learned that there are ways to alter aging. While we cannot delay chronological age, we can delay physiological age, at least in animal models. And, considering that has been one of the major quests of humanity all along, it’s quite exciting.

For example, we have known for about 80 years that calorie restriction—permanently cutting total calorie intake by 25 to 30 percent—can delay aging. But this really isn’t feasible for most people. So, DAB supports research to identify the biological pathways in the body affected by calorie restriction that lead to improved health and increased life span. In mouse studies, we are finding mimetics of calorie restriction—compounds that activate similar pathways as calorie restriction and thereby have similar effects. To me, that’s quite an accomplishment.

What does the Division of Aging Biology look for in a grant proposal?

Innovation is the main characteristic—research that is trying to open new fields, looking at something that nobody had thought about before. We also look for research that is especially relevant to aging because there’s hardly anything you could study in biology that doesn’t have a role in aging. Therefore, we need to be selective. For example, let’s say you’re studying cancer. With a few exceptions, cancer is an age-related disease, so that should be of interest to us. But much cancer research is on mutations and oncogenes and things of that nature, and there is another NIH Institute—the National Cancer Institute—that can fund those projects. The NIA wants to know why those mutations can occur in a child and nothing happens, but when they occur in an older person, they cause cancer. Something changes in the milieu where that cell is. That’s what is interesting to us.

Another example is related to cardiovascular disease. I could take my daughter to a fast food restaurant every day for a year, and guess who’s likely to die at the end? Me. My daughter is going to have long-term effects, but I’m the one who will immediately have the very serious health problems. Why? It’s the same diet, but it affects an older person differently than it does a younger one. We look for research that is both relevant to aging and addresses the aging part of it. So, if you’re studying cardiovascular disease, we expect you to be interested in why the aged environment is important.

What advice would you give to people who are interested in understanding aging biology research but do not have a science background?

I’d rather give advice to the researchers first. As a scientist, you should be able to explain your research to someone who doesn’t have a science background. It was always important to me that my mother understood what I was doing. My mom has no training in biology, but if I can explain my work so that she understands it, then I’m doing a good job. Researchers often don’t do a very good job of explaining what they do. They assume that it is too complicated, which is not always true. Or, they explain it in a way that only another scientist would understand.

The advice I would give to the public is that if they have the opportunity to talk to a scientist and don’t understand him or her, they should ask for clarification. Some scientists are very good about it, others are not so good. I can give you an example with my daughter. We went to a meeting when she was 7 years old, and one of the presenters showed a green fluorescent cell, a neuron, in the head of a roundworm. She asked me, “How do they put the green cell in that worm?” and I said, “Well, why don’t you ask the researcher?” At the end of the meeting, she went and asked him. This is a 7-year-old asking a well-known scientist, “How do you put the green cell inside the head of the worm?” But he was able to explain it in a simple way so that she understood, and that’s what we should be able to do.

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