Understanding – and increasing – calcium signaling could lead to new therapeutic strategies for age-associated inflammation.
Researchers have discovered a key driver of chronic inflammation that accelerates aging, a finding that could lead to longer, healthier lives and the possible prevention of age-related conditions such as heart disease and brain disorders.
The harmful inflammation is driven by improper calcium signaling in the mitochondria of certain immune cells, University of Virginia School of Medicine researchers found. Mitochondria are the power generators in all cells, and they rely heavily on calcium signaling [1].
Longevity.Technology: The UVA Health researchers found that, as we age, mitochondria in immune cells called macrophages lose their ability to take up and use calcium. This leads to chronic inflammation that drives aging and that is responsible for many of the ailments that afflict our later years – inflammaging.
The researchers believe that increasing calcium uptake by the mitochondrial macrophages could prevent the inflammation and its terrible effects; because macrophages reside in all of the body’s organs, including the brain, targeting them with appropriate drugs may help slow age-associated neurodegenerative diseases.
“I think we have made a key conceptual breakthrough in understanding the molecular underpinnings of age-associated inflammation,” said Bimal N Desai of UVA’s Department of Pharmacology and UVA’s Carter Immunology Center who led the study [2].
Desai added that the discovery, which has been published in Nature Aging provides potential treatment strategies to head off inflammatory cascades that lie at the heart of many cardiometabolic and neurodegenerative diseases.
Inflammaging 101
Macrophages are white blood cells that play critical roles in the immune system and good health. They swallow up dead or dying cells, allowing the removal of cellular debris, and they patrol for pathogens and other foreign invaders. In this latter role, they act as important sentries for the immune system, calling for help from other immune cells as needed. It has been known that macrophages become less effective with age, but it has been unclear why; Desai’s new discovery suggests answers.
Desai and his team say their research has identified a “keystone” mechanism responsible for age-related changes in the macrophages. These changes, the scientists believe, make the macrophages prone to chronic, low-grade inflammation at the best of times. And when the immune cells are confronted by an invader or tissue damage, they can become hyperactive – this drives inflammaging, the chronic inflammation that drives aging.
In addition, the UVA Health scientists suspect that the mechanism they have discovered will hold true not just for macrophages, but for many other related immune cells generated in the bone marrow. That means it may be possible to stimulate the proper functioning of those cells as well, potentially giving our immune systems a big boost in old age, when we become more susceptible to disease.
Chalk it up to research
Fixing inflammaging won’t be as simple as taking a calcium supplement. The problem isn’t a shortage of calcium so much, as the macrophages’ inability to use it properly. However, Desai’s discovery has pinpointed the precise molecular machinery involved in this process, and this means further research should be able to discover ways to stimulate this machinery in aging cells [1].
Desai credits the success of the research to interdisciplinary effort – which combined computational biology, immunology, cell biology and biophysics – as well as the determination of graduate student Phil Seegren who spearheaded the project.
“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,” Desai said [2].
[1] https://www.nature.com/articles/s43587-023-00436-8
[2] https://bit.ly/43XAZcC
