Univ. of Virginia, School of Medicine researchers discovery – a key driver of chronic inflammation causing ageing to accelerate in human bodies. This finding can potentially lead to a position where we could slow down our natural ageing clock and so live longer,healthier lives, where many age related conditions like heart disease and devastating brain disorders could be dlayed or even avoided all together.
The driver of this harmful inflammation is improper calcium signaling in the mitochondria of certain immune cells. Mitochondria are each of your cells power generators and each of these relies heavily on calcium signaling.
UVA Health researchers, led by Bimal N. Desai PhD, found that mitochondria in immune cells called macrophages lose their ability to take up and use calcium with age. This leads to the chronic inflammation responsible for many ailments that afflict us in our later years.
Researchers believe that increasing calcium uptake by mitochondrial macrophages could prevent the harmful inflammation and these terrible effects. Because macrophages reside in all of our bodies organs including the brain, targeting such “tissue resident macrophages” with appropriate drugs may allow us to slow age related neurodegenerative diseases.
Desai said “I think we have made a key conceptual breakthrough in understanding the molecular underpinnings of age associated inflammation,. This discovery illuminates new therapeutic strategies to interdict inflammatory cascades lying at the heart of many cardiometabolic and neurodegenerative diseases.”
Inflammation of Aging — ‘Inflammaging’
Macrophages are white blood cells that play critical roles within immune systems and so in turn, our good health. They swallow dead or dying cells, so allowing our bodies to remove cellular debris, they patrol for pathogens and other foreign invaders. In this latter role, they act as important sentries for immune systems, that can gather help from other immune cells, when needed.
Scientists knew that macrophages became less effective with age, but were 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 macrophages. These changes, they believe, make macrophages prone to chronic, low grade inflammation at the best of times. When immune cells are confronted by invaders or tissue damage, they can be hyperactive so driving “inflammaging” a chronic inflammation that drives aging.
There ios a further potential that UVA Health scientists suggest is the mechanism they have discovered will hold true not only for macrophages but many other related immune cells generated in bone marrow. This means it may be possibly to stimulate a proper functioning of those cells as well, potentially giving our immune systems a big boost into old age, the time we all become more susceptible to disease.
Fixing “inflammaging” won’t be a simple “Take a calcium supplement”. The problem isn’t a calcium shortage but the macrophages’ inability to use this properly. But Desai’s new discovery has pinpointed the precise molecular machinery in this process, so we should also be able to discover ways to stimulate this 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 controlling this mitochondrial process in different types of macrophages and then manipulate its wiring in creative ways for biomedical impact.”