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“What are you most excited about?”

Posted by on Monday, May 16, 2022 in Related Content, Spring 2022 .

A recent “Lab-to-Table Conversation” sponsored by School of Medicine Basic Sciences featured three Vanderbilt faculty members who discussed aging research and the latest findings from their groups. Here, we share their responses to the question, “What are you most excited about in your own research program?” (Responses edited for length and clarity.)

 

 

Rafael Arrojo e Drigo, PhD, assistant professor of Molecular Physiology and Biophysics

“We’re trying to understand how old cells are in different organs and the biological processes that occur as they go through their normal lifetime.

We’re beginning to understand how dietary interventions affect cell age. We know that caloric restriction in most animal models tends to extend the average life span of an animal. And the initial data that we have is that caloric restriction tends to prolong cellular lifetime — the cells tend to be longer lived. We think that the dietary interventions are signaling to cells not to focus on proliferation, but instead to focus on becoming better cells, changing the way they metabolize certain nutrients to achieve proper homeostasis.

We are also finding that caloric restriction tends to prolong the lifetime of cells throughout the body, at least in different organs that we looked at. I’m excited about dietary interventions that might actually trigger cells to be more resilient and potentially live longer.”

 

 

Kristopher Burkewitz, PhD, assistant professor of Cell and Developmental Biology

“We’re working on nutrient-sensing pathways, diet and cell biology, and the way that these processes interact with aging. We’re trying to unlock the reprogramming events that occur during pro-longevity interventions involving dietary restriction, when nutrient levels are low, so that we can develop small molecule therapeutics that do similar things.

One of the things that we know from worms all the way up to humans is that the inner structure of a cell and all its organelles are very dynamic. They change shape; they move around throughout the cell; and they even interact with each other in ways that are really important for how the cell as a whole functions.

We find that the dynamics of these organelle networks and their communication with each other are breaking down during the aging process. At the same time, we know that exposing cells or animals to scarce nutrient conditions such as when we are fasting, also dramatically reshapes the cell in ways that we predict are improving the quality of aging. So, we’re excited to probe how we can preserve these subcellular organelle structures and interactions as a mechanism of improving health during the aging process.”

 

 

Laura Dugan, MD, professor of Medicine in the Division of Geriatric Medicine

“Neurons and other long-lived cells rely on a process called autophagy (regulator of proteostasis and mitochondrial function) that recycles cell components, to conserve energy and to prevent buildup of toxic, damaged materials.

We’re excited because we’ve made a link between chronic low-grade inflammation, which happens in aging and in a lot of disease processes, and impaired autophagy in the brains of normal aging mice.

By doing a long-term anti-inflammatory treatment, we were able to improve autophagy and clearance of proteins. We think that’s important to preserve the health of neurons directly. It also preserved neurons near accumulated debris fields — extruded material that wasn’t degraded and that we think sets up a feed-forward inflammatory cycle that causes more damage to the brain and neuronal connections.

Since we don’t really replace neurons to any great extent, we’ve got to do everything we can to help them stay healthy, so we think this decrease in inflammation and improved autophagy could have big implications for CNS aging. We are also developing PET imaging tools to try to see this set of processes in model organisms and people.”

 

 

 

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