From Indiana Jones to the Lab Bench: My Journey to Understanding Aging
Have you ever wanted to live forever? Or perhaps stay young forever? This is what we study in the Sutphin lab here at the University of Arizona. This idea has captivated me since a young age when I first saw Indiana Jones and The Last Crusade. In this movie, the ultimate search is for the Holy Grail, which, when drunk from, provides everlasting life and restores youth. The Knights Templar guard the grail, drinking from it and gaining eternal youth. However, when one of the antagonists drinks from the wrong cup, he ages so rapidly that he turns to dust! The idea of living forever was so exciting for me that it helped shape my graduate career. I joined the Sutphin lab and discovered that they were already looking for a life-extending “Holy Grail” and had found a candidate! Dr. Sutphin discovered a molecule that extends the lifespan of a model organism, demonstrating great therapeutic potential. This molecule, 3HAA, a natural product of tryptophan metabolism, is part of what I study. Tryptophan is an essential amino acid, a building block for a protein, necessary for bodily function. We are hoping to further understand the beneficial effects of 3HAA and how we might enhance these and translate them into therapeutics for humans.
My time in the Sutphin lab has been an incredible journey. I began as an undergraduate, working on a similar project, but with a different primary focus, stress response. When most people hear stress, they think of the day-to-day challenges and often attribute their stressful lives to accelerated aging. In a sense, this is true - cellular stress does accelerate aging. This project explored the relevance of copper in that, as well as the combination of multiple different forms of stress. After completing my undergraduate degree, I was able to return to the lab and begin working on this project, which has been an incredible experience. Now I am like Indiana Jones, performing research, albeit closer to home, that will hopefully have a great impact on society.
We are in search of a Holy Grail that may grant lifespan extension, healthspan improvement, and maybe even reverse the aging process. However, along this journey, we must try every “cup”—finding which ones increase the rate of aging so that we might know what to avoid. This is part of our scientific process. By learning about the different types of stress the body encounters, we can understand more about how the natural processes of aging occur. In this process, we have learned many things. For example, some types of stress, like exposure to certain metals in very small doses, can promote resistance to other forms of stress down the line.
I study the interactions of 3HAA and a form of iron. Since we know 3HAA is good, the idea is that the iron may be able to enhance its effects or promote the accumulation of 3HAA, which is what causes the lifespan extension. So far, I’ve figured out that a particular form of iron, FAC, extends the lifespan in our model about half as well as 3HAA. We think that it might be acting with the 3HAA to produce this extension. So maybe the Holy Grail, at least for the model, is filling up a few cups and drinking them together!
Understanding the processes of aging can have much more close and tangible benefits than something as extreme as eternal life. The majority of the leading causes of death in the US, including cancer, heart disease, and Alzheimer’s disease, are all age-associated diseases. By understanding the molecular drivers of aging—those that accelerate aging and those that slow it—we can help further develop treatments for these diseases and help lessen the burden on an ever-stressed healthcare system with an increasingly aging population. We’ve already seen some of these benefits with 3HAA, which appears to boost immune function in two models, extend lifespan, and even have potential anti-cancer effects. I’m excited to continue this research and hopefully unlock the secret to eternal youth as I pursue my PhD in Molecular and Cellular Biology.