Improper Calcium Signaling in Immune Cells Contributes to Chronic Inflammation, Accelerates Aging
A team from the University of Virginia School of Medicine has discovered that improper calcium signaling in the mitochondria of certain immune cells contributes to chronic inflammation that accelerates aging. They propose that enhancing calcium uptake in these cells could help to slow down age-related diseases. The findings are published in the scientific journal Nature Aging.
Key Driver of Chronic Inflammation Discovered
University of Virginia School of Medicine researchers have discovered a key driver of chronic inflammation that accelerates aging. That finding could let us slow the clock to live longer, healthier lives, and may allow us to prevent age-related conditions such as deadly heart disease and devastating brain disorders that rob us of our faculties.
Improper Calcium Signaling in Mitochondria
The team at UVA Health, under the leadership of Bimal N. Desai, PhD, found that the mitochondria in macrophages, a type of immune cell, lose their ability to absorb and utilize calcium as they age. They demonstrated that this issue leads to the chronic inflammation accountable for many health problems associated with old age.
Enhancing Calcium Uptake to Deter Inflammation
The researchers propose that enhancing calcium uptake by these mitochondrial macrophages could deter this harmful inflammation and its severe consequences. Given that macrophages are present in all our body organs, including the brain, directing targeted drugs towards such “tissue-resident macrophages” may enable us to slow age-related neurodegenerative diseases.
The Inflammation of Aging – ‘Inflammaging’
Macrophages are white blood cells that play critical roles in our immune systems and, in turn, our good health. They swallow up dead or dying cells, allowing our bodies to remove cellular debris, and patrol for pathogens and other foreign invaders. In this latter role, they act as important sentries for our immune systems, calling for help from other immune cells as needed.
A Keystone Mechanism in Aging
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 what is known as “inflammaging” – chronic inflammation that drives aging.
The Way Forward
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. But Desai’s new discovery has pinpointed the precise molecular machinery involved in this process, so we should be able to discover ways to stimulate this machinery in aging cells.
Aging Findings Published
The researchers have published their findings in the scientific journal Nature Aging.
Reference: “Reduced mitochondrial calcium uptake in macrophages is a major driver of inflammaging” by Philip V. Seegren, Logan R. Harper, Taylor K. Downs, Xiao-Yu Zhao, Shivapriya B. Viswanathan, Marta E. Stremska, Rachel J. Olson, Joel Kennedy, Sarah E. Ewald, Pankaj Kumar and Bimal N. Desai, 5 June 2023, Nature Aging.
The research team consisted of Seegren, Logan R. Harper, Taylor K. Downs, Xiao-Yu Zhao, Shivapriya B. Viswanathan, Marta E. Stremska, Rachel J. Olson, Joel Kennedy, Sarah E. Ewald, Pankaj Kumar, and Desai. The scientists reported that they have no financial interests in the work.
The research was supported by the National Institutes of Health, grants AI155808, GM108989, GM138381, P30 CA044579 and T32 GM007055-46, and by the Owens Family Foundation.