Cardiovascular: Constructing a Younger-performing Heart

Ben Boulden

Gohar Azhar, M.D., is exploring the consequences of having a young heart in an old body, and that’s not a metaphor.

By changing one protein in the cardiac muscle of the heart,  Azhar and her colleagues have been able to make the heart perform in an old mouse as though its chronological age was much less. The team has also been able to do the reverse — age a heart at an accelerated rate faster than the body around it.

“We were the first ones to do these experiments in Dr. Jeanne Wei’s laboratory. It’s a slight change of a single protein that’s changing the entire organ, but not the rest of the body” Azhar said. “That’s exciting, and later on we discovered even more important things about this transcription factor, which is called SRF — Serum Response Factor.”

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Azhar is an associate professor in the UAMS College of Medicine’s Department of Geriatrics and director of the Cardiovascular Aging Program in the UAMS Donald W. Reynolds Institute on Aging.

The heart usually gets stiffer as it ages, and the old cardiac tissue doesn’t relax as well or as rapidly as it once did. That greater rigidity means it doesn’t have the capacity to dilate and hold all the blood in the heart that it could, even if its ability to pump blood out might be equally as good as that of young adults. Having less flexibility and less tolerance for stress also raises the risk for heart attacks and heart failure.

Effectively making the heart younger by modulating the level of SRF, Azhar and her research team can give it a greater capacity to tolerate stress. However, much work remains to be done to perfect it.

“If you inhibit SRF too much, it results in dilated cardiomyopathy and death,” she said. “A very mild reduction results in a better-functioning old heart. A mild increase results in accelerated aging. It’s very interesting that there is a small window within which a mild increase or a mild decrease of SRF can effectively produce an old heart in a young body or a young heart in an old body. However, moderate reductions or moderate increases of SRF can be lethal.”

The team is now endeavoring to better define that window and understand the SRF protein mechanism more precisely. They also are testing drugs in cells that inhibit it and researching ways to minimize the effect of SRF manipulation on the rest of the body.

SRF plays an important role in skeletal muscle as well as cardiac muscle, so Azhar also works closely with Robert Wolfe, Ph.D., director of the Center for Translational Research in the Institute on Aging.  Their focus is on possible nutritional interventions that can improve the health of both cardiac and skeletal muscle. Azhar and Wolfe both conduct their research through the Claude D. Pepper Older Americans Independence Center.

“Our objective is not to prolong life,” Azhar said. “It’s to make people as independent and functional as we can, and to have a better quality of life, for as long as possible. We want them to have good cognition and be able to engage in work or hobbies, participate in society and enjoy life to the fullest. They have so much to give in wisdom and experience in return.”