VCU team explores epigenetics as cause of adverse drug reactions in elderly

A photo of an old person's hand with a hospital wrist band being held by a younger person's hand.
Older patients are almost seven times as likely to be hospitalized for drug reactions than younger ones. Researchers from VCU’s pharmacy and medical schools are examining the role of epigenetics.
Greg Weatherford
Director of Communications
VCU School of Pharmacy

A VCU School of Pharmacy research team is studying how aging affects the ways drugs interact with the body. The results may help doctors better manage medications in older patients. 

The aim is to better understand why older people seem to metabolize drugs more slowly, with the goal of someday seeing fewer adverse drug reactions and hospitalizations among the elderly, said the principal investigator, Joseph McClay, Ph.D., an assistant professor in the VCU School of Pharmacy’s Department of Pharmacotherapy and Outcomes Science. 

Older patients are almost seven times as likely to be hospitalized for adverse drug reactions than younger ones, according to a 2006 study in the Journal of the American Medical Association. A separate study in the United Kingdom found that adverse drug reactions contributed to 6.5% of hospital admissions and primarily occurred in older patients.

The causes for these disparities are not well known, McClay said. 

The study, supported by a $454,000 grant from the National Institute on Aging, will explore how genetic factors that are turned on and off by the body — a process known as epigenetics — affect how the body interacts with medications as it ages. 

The body’s genes, its DNA, do not change over time. But its epigenetics, how the body expresses those genes, does. The VCU team will begin the process of tracking how these epigenetic changes affect the body’s reaction to drugs. 

McClay and his colleagues — Elvin Price, Pharm.D./Ph.D., and Matthew Halquist, Ph.D., in the VCU School of Pharmacy and Mikhail Dozmorov, Ph.D., and Patrick Beardsley, Ph.D., in the VCU School of Medicine — and a team of graduate students will begin by mapping age-related changes in key genes using samples of livers from aged mice from the National Institute on Aging. 

This map of epigenetic changes, McClay said, will help researchers understand how the liver, the body’s main organ for metabolizing drugs and other outside chemicals, could interact with medicines in older bodies. 

Once the mapping is complete, the team plans to focus on a gene known as CYP2E1, which is part of the liver’s system of metabolizing chemicals such as drugs and alcohol and has been shown by the VCU team and others to be expressed differently in older bodies. 

In particular, the VCU researchers will study how chlorzoxazone, a drug metabolized by CYP2E1, is affected. If livers from older mice metabolize the drug more slowly, as McClay and his team predict, this could lead to greater understanding of the reasons that older humans are affected differently by medications. and iIn time this could lead to better medication dosing in elderly patients.

“That is the point, in the end,” McClay said. “We want to keep people healthy.” 

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