January 2014

Project Seeks to Understand Molecular Mechanisms That Cause Aging

Aging

It’s no secret that as we age, our bodies change. Though the signs of aging — from wrinkles to graying hair to changes in metabolism — vary from person to person, the truth is that every day everyone is getting a little bit older.

And the aging process, as we also know, can have implications for our health. As the National Institute on Aging (NIA) succinctly puts it, “getting older can come with a variety of health challenges.” Besides the usual aches and pains that aging can bring, there are a number of diseases typically seen in older populations. These include osteoporosis, osteoarthritis, cardiovascular issues, and Alzheimer’s disease.

One Children’s Hospital researcher, Marc Vermulst, PhD, of the Center for Mitochondrial and Epigenomic Medicine, is very interested in the mechanics of aging. Much of Dr. Vermulst’s research has focused on better understanding the aging process, and he recently received a four-year grant from the NIA to investigate the role biological errors play in aging.

“Most diseases that are endemic in our society are age-related diseases — cancer, Alzheimer’s disease, Parkinson’s disease — so there’s something about the aging process that predisposes different types of tissues to these diseases, so if we can find that thing we might be able to stave off some of these age-related diseases or push them out of our natural lifespan,” Dr. Vermulst said.

The NIA grant will support Dr. Vermulst’s investigation of the role non-genetic errors made during cell transcription and translation play in age-related diseases. This is a new, “non-DNA centric way to understand how aging results ultimately in age-related diseases,” Dr. Vermulst said. He has been working with the National Cancer Institute’s Jeffrey N. Strathern, PhD, and the University of North Carolina’s Dorothy Erie, PhD, on the project.

Dr. Vermulst developed a number of novel assays to conduct this research, which he hopes “may significantly deepen our understanding of aging and age-related pathology and help identify new targets for treatments or prevention strategies in the clinic.” The investigators are currently focused on four diseases: Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and Amyotrophic Lateral Sclerosis, also known as ALS or Lou Gehrig’s disease.

In their experiments, Dr. Vermulst and his team increased the error rate of transcription in living cells and found “features that are indicative of accelerated aging,” he said. For example, Dr. Vermulst pointed out that some age-related diseases are caused by an aggregation of proteins. And as the researchers increased the error rate of transcription, they also increased the rate at which these proteins aggregated, which suggests that a link exists between transcription errors and age-related diseases.

While his investigation is basic and clinical applications of the work remain in the future, Dr. Vermulst says the project’s focus on establishing a better understanding of the mechanisms of aging could lead to future treatment strategies. “If we understand the reason why aging causes age-related diseases, we can pinpoint targets for intervention,” he said.

To learn more about the groundbreaking research being conducted at the Center for Mitochondrial and Epigenomic Medicine, visit CMEM’s website.

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