UVA School of Medicine researchers have discovered a key driver of chronic inflammation that accelerates aging.
They call it “inflammaging.”
The discovery could enable humans to slow the clock and live longer, healthier lives, as well as prevent age-related conditions including heart disease and devastating brain disorders that rob us of our faculties.
The key is improper calcium signaling in the mitochondria of certain immune cells. Mitochondria, the power generators in all cells, rely heavily on calcium signaling.
Led by Dr. Bimal N. Desai, the UVA researchers found that the mitochondria in the immune cells called macrophages lose their ability to take up and use calcium with age. This leads to chronic inflammation responsible for many ailments that affect human health as we get older.
“I think we have made a key conceptual breakthrough in understanding the molecular underpinnings of age-associated inflammation,” Desai, of UVA’s Department of Pharmacology and UVA’s Carter Immunology Center, said. “This discovery illuminates new therapeutic strategies to interdict the inflammatory cascades that lie at the heart of many cardiometabolic and neurodegenerative diseases.”
Increasing calcium uptake by the mitochondrial macrophages could prevent the harmful inflammation and its terrible effects. Targeting such “tissue-resident macrophages” with appropriate drugs could slow the progress of age-associated neurogenerative diseases, because macrophages reside in all organs of our bodies.
Macrophages are white blood cells that swallow up dead or dying cells, which allows our bodies to remove cellular debris and patrol for pathogens and other foreign invaders. Macrophages act as important sentries for the immune system, calling for help from other immune cells.
Scientists have known that macrophages become less effective with age, but were unsure why. Desai and his team identified a “keystone” mechanism responsible for age-related changes in the macrophages. The 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, which drives “inflammaging” – chronic inflammation that drives aging.
However, calcium supplements will not fix “inflammaging,” because the problem is not a shortage of calcium so much as the macrophages’ inability to use it properly. Desai’s discovery pinpointed the precise molecular machinery involved in this process, so we should be able to discover ways to stimulate the machinery in aging cells.
“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.”
Funded by grants from the National Institutes of Health, Desai and his team’s research results are published in the scientific journal Nature Aging.
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Rebecca Barnabi
