Lindsay De Biase, PhD

What inspired you to pursue aging research?

The human brain with its complex cellular circuits is often compared to a very specialized biological computer. Yet, the brain faces the incredible challenge of needing to maintain its circuits over a very long operational life. You can’t simply trade in your brain for an upgraded model every 5-10 years the way we do with computers. It’s a fascinating challenge to try and understand how the different populations of cells in the brain work together to keep us thinking and engaging with our surroundings for 50, 70, 90 years. By studying aging, we of course hope that we can learn how to preserve the integrity of this organ that plays an outsize role in shaping our identity. But I also believe that we will uncover factors that promote cellular and circuit resilience that can have applications in many fields such as neurodegenerative disease, stroke, and brain injury.

In your view, what does AFAR mean to the field, and what does it mean, for you, to receive an AFAR grant now?

AFAR is a fantastic catalyst for the field of aging research. As a relatively new investigator, AFAR played an instrumental role in helping me to establish a research program that focuses on the role of non-neuronal cells in CNS aging. I received a Glenn Foundation and AFAR Grant for Junior Faculty that enabled us to gather preliminary data for our first NIH grant submissions. AFAR support also allowed us access to colonies of aging rodents maintained by the NIH, which is invaluable for basic researchers aiming to uncover the cellular and molecular mechanisms of CNS aging. AFAR also provided highly stimulating opportunities to interact with and learn from other aging researchers via their annual grantee symposium. This new source of support from the McKnight Brain Research Foundation / AFAR allows us to launch novel lines of CNS aging research and use cutting-edge approaches to link our cellular and molecular-level findings with cognitive performance and behavior. I am honored to receive this support and very excited by the potential of this new line of investigation to expand our understanding of how non-neuronal cells shape cognitive aging.

What is exciting about your research’s potential impact?

I think our research is “outside the box” from a couple perspectives. First – we study non-neuronal cells, or glial cells. Neurons are electrically excitable and form information-storing circuits through their synaptic connections with one another. So it might seem counter-intuitive to try and understand cognition by looking at cells that are notelectrically excitable and that don’tform synapses. Yet, substantial evidence from the last 10-15 years shows that these glial cells can potently regulate the function of neurons and synapses in ways that have a big impact on behavior and cognition. This is an exciting frontier because glial cells are likely to be more therapeutically “tractable” than neurons. The second out-of-the-box piece of this research project is our study of glial interactions with the extracellular matrix. The role of the extracellular environment in synapse function and integrity has not received a lot of attention and this area is ripe for new discoveries.

How would you describe your research to a non-scientist?

We study non-neuronal, or glial, cells in the central nervous system. For many years these cells were thought to do little more than provide structural support for information-storing neurons in the brain. (The term glia derives from the Greek word for “glue”). Yet we now recognize that glial cells play essential roles in maintaining neuronal health and fine-tuning their function. The field is just at the beginning of mapping out exactly how these cells can regulate cognition and behavior and how they might be harnassed in a wide variety of therapeutic contexts.

AFAR turned 40 in 2021. What is your vision for the next 40 years of healthy aging?

As a neuroscientist, I often wish that I had more knowledge about aging of other organ systems and the dialog between the CNS and the rest of the body during aging. There is exciting headway being made in terms of increased interaction between aging researchers that study distinct organ systems, and exciting findings at the intersections of these fields. I think aging research will benefit immensely from further nurturing of cross-pollination between aging research disciplines. Many challenges persist in trying to translate basic research findings to the human CNS. I also hope to see substantial progress in the next 40 years in translational pipelines, fostered by greater dialog between clinicians and basic scientists as well as technical innovation. I also love seeing expanding knowledge about how non-pharmaceutical interventions (such as lifestyle changes) shape healthy aging. I hope as a human society we can support many individuals in pursuing such changes, especially those who may not have easy access to health care.