Aging and the Aryl Hydrocarbon Receptor in the Regulation of Drug Metabolism

Authors

Sara Abudahab, Virginia Commonwealth University

Original Publication Date

2022

Document Type

Presentation

Comments

First place winner of the 8th Annual VCU 3MT® Competition, held on October 7, 2022.

Abstract

By 2050, more than two billion people will be 60 or older, outnumbering youth for the first time in history. With increasing life expectancy comes a growing medication burden: nearly 40 percent of older adults take four to nine drugs daily, and almost one in five take ten or more. As a result, older adults are seven times more likely to experience adverse drug reactions requiring hospitalization. In her Three Minute Thesis presentation, Sara Abudahab explains how her research seeks to reduce these risks.

Trained as a pharmacist, Abudahab investigates how pharmacogenetics—prescribing based on a patient’s genes—can make medications safer. Yet genetics alone cannot explain why drug responses shift across the lifespan. Her work examines age-related epigenetic changes, chemical tags that switch genes on or off. Focusing on the liver receptor AHR, which regulates enzymes that break down medications, she and her team discovered that a key epigenetic mark declines with age in mouse liver tissue.

Abudahab’s findings point toward an “epigenetic page” within a personalized medicine passport—one that adapts as individuals age. Ultimately, the goal is medication strategies tailored not only to a person’s DNA, but also to the dynamic biological changes that come with growing older.

Transcription

Did you know that in 2050 there will be around two billion people aged 60 or older? In fact, it is estimated that there will be more older adults than youth aged 10-24. As a society, we are living longer, and this is all good news, right? Yes, but, aging comes with some difficulties. For example, one study found that around 40% of older adults use between four and nine medications. While 18% use 10 or more on a regular basis. To make matters worse, the elderly were found to be seven times more likely, not only to experience a drug reaction but to experience one that needs hospital care.

As a pharmacist I have always been interested in finding ways to increase the safety of medications and in our lab, we focus on pharmacogenetics, which is the study of how our genes affect the way we respond to medications. Think of pharmacogenetics as your drug passport, where we would test certain genes in your body, and depending on the results we would give you a specific drug or a specific dose that is tailored to you! But what if I told you that on top of your genes there are certain tags or marks that we call “epigenetic marks”?

They are basically “switches” telling your body among other things, which genes to turn ON and which genes to turn OFF. And very interestingly, we lose and gain some of these epigenetic marks with age in a very systematic pattern. To the point where we can actually use them to predict very accurately the age of a person and scientists call them “epigenetic clocks”.

Applying this amazing concept to my own research, we are investigating these epigenetic marks in a liver protein called AHR. AHR regulates the production of liver enzymes that break down the medications that we consume. And we found using mice livers, that one epigenetic mark actually decreases with age at the AHR gene, and now we want to find to which extent does that affect drug metabolism with age.

So in a nutshell, think of this as an additional page that can be added to your pharmacogenetic passport, a page that will be updated as you age. So not only will you be treated differently than others, even your 60-year-old self could be treated differently than you would now!

Rights

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