Researchers Reveal Mechanism that Impairs Blood Flow with Aging

Erika Boerman, PhD

The Physiological Society’s Journal of Physiology recently published a study led by Erika Boerman, identifying an age-related cause of arterial dysfunction.

 

 

With the world’s elderly population expected to double by 2050, understanding cardiovascular disease, the No. 1 cause of death worldwide, is often highlighted and now University of Missouri researchers have identified an age-related cause of arterial dysfunction, a finding that could lead to future treatments.

“Aging affects everyone and causes changes throughout our bodies,” said Erika Boerman, a post-doctoral fellow in the Department of Medical Pharmacology and Physiology at the MU School of Medicine and lead author of the study. “We found that older arteries had a significantly lower number of sensory nerves in the tissues surrounding them and they were less sensitive to an important neurotransmitter responsible for dilation.”

Boerman’s study focused on mesenteric arteries ― a type of artery that supplies blood to the small intestines ― of mice that were 4 months and 24 months old. These ages correspond to humans in their early 20s and mid-60s, respectively. Without stimulation, the diameter of the blood vessels of both younger and older mice was approximately the same. However, when stimulated to induce dilation, differences between the age groups became apparent.

“The younger arteries dilated as expected,” Boerman said. “However, when we performed the same stimulation to the arteries of older mice, the vessels did not dilate. When we examined the presence of sensory nerves, we noted a 30 percent decrease in the amount surrounding the older arteries compared to the younger arteries.”

Additionally, the researchers found that even when purposefully exposing older mesenteric arteries to defined amounts of the neurotransmitter calcitonin gene-related peptide, or CGRP, the arteries’ ability to dilate was greatly reduced.

“Poor neurotransmitter function and a reduced presence of sensory nerves surrounding older vessels lead to age-related dysfunction of mesenteric arteries,” Boerman said. “The importance of this discovery is that if we can identify why this happens to mesenteric arteries, it may be possible to prevent the same thing from happening to other blood vessels throughout the body.”

More research is needed to understand why aging affects sensory nerve distribution and neurotransmitter performance. However, identifying this new mechanism of vascular dysfunction opens the door for future studies that could eventually lead to the treatment of health issues such as stroke and cardiovascular disease.

The study was published in The Physiological Society’s Journal of Physiology.

Blood Vessels Can Actually Get Better With Age

 

Although the causes of many age-related diseases remain unknown, oxidative stress has been linked to cardiovascular and neurodegenerative diseases including diabetes, hypertension and age-related cancers.

However, researchers at the University of Missouri recently found that aging actually offered significant protection against oxidative stress, suggesting that aging may trigger an adaptive response to counteract the effects of oxidative stress on blood vessels.

“Molecules known as reactive oxygen species, or ROS, play an important role in regulating cellular function,” said Steven Segal, at the MU School of Medicine and senior author of the study. “However, the overproduction of ROS can help create a condition referred to as oxidative stress, which can alter the function of cells and interfere with their growth and reproduction.”

To understand the effects of aging on the function of blood vessels when they are exposed to oxidative stress, Segal’s team studied the inner lining, or endothelium, of small resistance arteries. Resistance arteries are important to cardiovascular function because they regulate both the amount of blood flow into tissues and systemic blood pressure.

“We studied the endothelium from resistance arteries of male mice at 4 months and 24 months of age, which correspond to humans in their early 20s and mid-60s,” Segal said. “We first studied the endothelium under resting conditions and in the absence of oxidative stress. We then simulated oxidative stress by adding hydrogen peroxide.

When oxidative stress was induced for 20 minutes, the endothelial cells of the younger mice had abnormal increases in calcium when compared to the endothelial cells of the older mice. This finding is important because when calcium gets too high, cells can be severely damaged.”

When oxidative stress was extended to 60 minutes, Segal’s team found that the death of endothelial cells in the younger mice was seven times greater than those from the older mice. These findings indicated that with advancing age, the endothelium had adapted to preserve cellular integrity when confronted with oxidative stress.

“This finding contrasts with the generally held belief that the functional integrity of the endothelium is compromised as we age. Our study suggests that blood vessels adapt during the aging process to regulate ROS and minimize cell death when subjected to an abrupt increase in oxidative stress. This adaptation helps to ensure that the arteries of older individuals can still do their jobs.”

The study was published in the Physiological Society’s Journal of Physiology.