Inflammation: Discovery Could Slow Down Aging

The study indicates that improper calcium signaling in the mitochondria of certain immune cells is responsible for driving harmful inflammation. This is important because the mitochondria can be seen as the power generators in all of our cells, and they rely heavily on calcium signaling. The UVA researchers found that the mitochondria in macrophage immune cells lose their ability to take up calcium with age, which leads to chronic inflammation that is responsible for many of the ailments that afflict us in older years.

The team believes that increasing mitochondrial macrophage uptake of calcium could help to prevent this harmful inflammation and the resulting horrible effects. As macrophages reside within all of our bodily organs which includes the brain, targeting tissue resident macrophages with appropriate medications may also allow us to slow down age-associated neurodegenerative disease. 

“I think we have made a key conceptual breakthrough in understanding the molecular underpinnings of age-associated inflammation,” said Bimal N. Desai, Ph.D., of UVA’s Department of Pharmacology and UVA’s Carter Immunology Center and study lead. “This discovery illuminates new therapeutic strategies to interdict the inflammatory cascades that lie at the heart of many cardiometabolic and neurodegenerative diseases.”

Macrophages are white blood cells that play critical roles in the immune system, which promote good health by “eating” dead or dying cells, this allows the body to remove cellular debris, and guard against foreign invaders and other pathogens. They act as sentries on patrol for the immune system and call for help from other immune cells as required. 

Although it is known that macrophages become less effective with age, the reasons why have been less clear. This research indicates possible answers, identifying a keystone mechanism that is responsible for age-related changes in the macrophages, and these changes are believed to make the macrophages susceptible to chronic, low-grade inflammation even at the best of times. When these immune cells are confronted by an invader of damaged tissue they can become hyperactive, and this hyperactivity known as inflammaging is the chronic inflammation that drives aging. 

The researchers believe that the mechanism discovery will hold true for many other related immune cells generated in the bone marrow, meaning that we may be able to stimulate the proper function of those cells as well to potentially give the immune system a boost in older age when we need it the most as we become more susceptible to disease. 

Addressing this inflammaging will not be simple, the problem is not a shortage of calcium so much as the inability to utilize it properly. However, this discovery identified the molecular machinery involved which opens paths to discover new ways to stimulate the machinery in aging cells to provide tangible anti-aging health benefits. 

“This highly interdisciplinary research effort, at the interface of computational biology, immunology, cell biology, and biophysics, wouldn’t have been possible without the determination of Phil Seegren, the graduate student who spearheaded this ambitious project,” Desai said. “Now, moving forward, we need an equally ambitious effort to figure out the wiring that controls this mitochondrial process in different types of macrophages and then manipulate that wiring in creative ways for biomedical impact.”