What inspired you to pursue aging research?
Aging is fascinating. It is inescapable and experienced by everyone. Research in recent decades has demonstrated that aging is not a nebulous concept, but something definable and akin to a disease. We know that there are hallmarks of aging, some of which can be partially reversed. Yet the biological mechanisms that define aging are elusive. This is particularly interesting in the case of stem cells, which are typically pools of rejuvenation that keep our tissues healthy. However, what happens when the stem cells themselves become aged? Furthermore, how does a chemical process, such as metabolism, become aged? I am inspired by these looming questions and the potential to have an impact on a fundamental aspect of life: aging.
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 unifying organization that brings researchers from all disciplines together to create novel solutions to longstanding problems. As a junior investigator starting my independent research lab, receiving funding from AFAR is extremely impactful. It not only enables my lab to continue growing but also allows the initiation of new projects specifically aimed at stem cell aging. The data gathered during this funding period will set the foundation for new grants, papers, and students. The AFAR Junior Faculty grant opens the door to new opportunities to expand my collaborative network, interact with experts in the field of aging, and establish aging as a core research aim in the Gilchrist lab.
What is exciting about your research’s potential impact?
My research seeks to uncover how the tissue microenvironment supports and exacerbates metabolic dysregulation, which is a hallmark of stem cell aging. By identifying specific external-internal signaling mechanisms, also referred to as mechanometabolic signaling, we aim to pinpoint potential targets for therapeutic intervention in the fight against aging. This approach is analogous to fighting cancer, where many therapeutics have been developed to target upstream factors such as the tissue environment. To develop similar strategies to combat aging, the Gilchrist Lab seeks to understand how the aging of local tissue contributes to the aging of the entire system.
How would you describe your research to a non-scientist?
Stem cells can do many things. They can turn into other cells, create more stem cells, or simply become dormant. Each of these fates has specific energy requirements from the cell metabolism. The specific fate decision is mediated by the tissue environment in which the stem cell lives. However, with age, the tissue environment is significantly altered. This can lead to altered signals to resident stem cells and contribute to abnormal stem cell functionality. A hallmark of age-related stem cell dysfunction is the change to cellular metabolism. As cells age, the chemical processes that provide energy to the cell become less efficient and produce toxic by-products. The Gilchrist lab seeks to understand how signals from the aged environment support and exacerbate aging of cellular metabolism and disruption of ‘youthful’ stem cell function. In our lab, we create synthetic tissues with tunable mechanical and chemical properties that mimic the signals of the young and aged tissue environments. Using synthetic tissues, we expose cultured stem cells to defined young and aged signals in order to identify features of the tissue environment that lead to the aging of cellular metabolism. The ultimate goal is to understand what drives aged stem cells, which can do many things, to do one specific thing.
