Ask the Expert: University of Alabama at Birmingham Nathan Shock Center Co-Director Thomas W. Buford, PhD, discusses the center's focus on the energetics of aging

There are eight Nathan Shock Centers in the Biology of Aging across the country, funded by the National Institute of Aging (NIA) of the National Institutes of Health (NIH). The centers provide leadership in the pursuit of basic research into the biology of aging. Each center brings unique expertise under the leadership of respected experts in the field. AFAR, which manages the Nathan Shock Centers of Excellence in the Biology of Aging Coordinating Center (NSC3) (U24AG056053), will highlight the work of these centers through this series*.

Since 2018, Dr. Buford has served in the UAB Nathan Shock Center of Excellence in Aging, including as co-director since 2020.

Describe the Cores that support the UAB Nathan Shock Center and its mission.

The focus of our Shock Center aligns with our theme of the energetics of aging. If you look at the biology of aging across species, one of the most consistent phenomena is energy production and utilization. Efficient energy production and utilization is a requirement for healthy aging. Each of our Cores are geared around that. Like the other centers, an Administrative Core facilitates the program and brings in new investigators in the field of aging. We have a Research Development Core, which supports pilot exploratory studies and helps to develop new investigators. Our three main research Cores are the Mitochondrial Health Assessment Core, the Organismal Energetics Core, and the Data Analytics Core.

The Mitochondrial Health Assessment Core supports innovative studies around the influence of the mitochondria—which, as those scientists would argue, most directly impacts energy production. Using a number of innovative assays, the Core can take samples and tissues from a wide variety of organisms from labs within and outside UAB. This Core has a strong user base and strong collaboration base across the country.

The Organismal Energetics Core focuses on work conducted onsite, where the Core measures energy production at the whole animal level, including not only energy utilization but also energy intake. The Core has a variety of measures for food intake, activity, body temperature—all the factors that influence energy production and utilization. The organisms researched include flies, worms, mice, and rats, among others. The Core is also just starting a new focus on the impact of circadian rhythms on energy utilization and production. As most humans know, our energy utilization patterns differ greatly as we get older. Researchers in this Core are looking at how circadian rhythms impact biological aging across the lifespan and how these things vary across the lifespan.

Our Core perhaps most unique to the consortium is the Data Analytics Core. This Core is led at Indiana University by David Allison, PhD. The Core provides a variety of basic biostatistical support services for pilot projects and explore high-level novel analytic approaches for biologic data sets—analyzing data from published lifespan curves, effects of prominent treatments, and recreating or reviewing existing data sets and analyses. They’re also in discussions about how we can pool existing resources and data sets across Shock Centers. This type of Core is typically associated with clinical research. For a basic science center, this type of Core is quite innovative.

What are the most promising discoveries coming out of your center?

We’ve had some important publications in the past few years. One that involves a variety of people from around the country, Victor M. Darley-Usmar, PhD, and colleagues developed a novel approach to measure mitochondria respiration in frozen samples. This is a big translational breakthrough for the field. It’s very difficult when you have to measure cellular function only in fresh tissue. Being able to take samples from frozen tissues opens up our data pool and expands the number of organisms—including humans—that we can include in the research.

Another technique from Scott Ballinger, PhD, uses mononuclear exchange mice. His group created a model where you can exchange the nucleus and the mitochondria across models. So you could have model A with the nucleus of model A and the mitochondria model A, and then you can have a model with A and B, one with B and A, B and B, et cetera. This isolates the impact of the mitochondria itself.

Dr. Allison’s group published a collaboration between the Data Analytics Core and the Organismal Core about caloric restriction, which is a big topic in aging. That research looked at the benefits of caloric restriction as mediated not via energy intake, but via energy imbalance, which differs from how most researchers think about this. Typical thought suggests that reducing the calories taken in affects longevity, and this research shows us that maybe it's not quite that simple.

How did aging show up for you as something that you wanted to study, especially preclinically?

Aging, for me, showed up when I was in grad school. I was an exercise and skeletal muscle physiologist. At the time, there was a big focus on sarcopenia, which is the loss of muscle mass and strength as we age. In the community, I sometimes saw older people having trouble at the grocery store or things like that. My original questions were how do we stop that? How do we prevent that? I always wanted to do things that ultimately help people. For me, grad school was where I got started thinking about aging and kept going from there.

What are the biggest obstacles your Center’s work is facing?

Scientifically speaking, because the regulatory environment that we all work in continues to get more and more complicated, time for open discussion or collaboration is limited. Meeting without a preplanned agenda—finding time in all our schedules to have open dialogue to simply talk science—that can be a challenge at times. Also, we also continue to look for avenues to increase collaboration across the Shock Center Network.

Where do you see things in 10 years for aging research?

In 10 years, my hope would be that the things that we’re working on in the basic science space today work themselves into the clinical research space and are being evaluated to try to help humans. Then, in 10 years, basic scientists would have a whole new path of opportunities to explore. One that’s particularly interesting for us is the impact of circadian rhythms. For decades, we’ve conducted aging experiments without taking those into account. If you run tests on animals during their dark cycle, you’re essentially testing them all when they should be sleeping. How do we take that into account? What is the impact of calorie restriction alone versus the impact of fasting and stopping each night before your body goes into hibernation? I’d like to see that issue grow out from our research. In general for the field, translating some things that people are talking about now like aging clocks and understanding more about epigenetic manifestations of biological age versus chronological age. If we were to measure that in humans more reliably, we could use the information in a clinically relevant way. For each of these things, you see an intervention in animals that shows tremendous promise. That jump to humans is typically not as simple as you would think, particularly if it involves behavior in any way.

*The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.