University of Virginia School of Medicine researchers have made a groundbreaking discovery of a key mechanism that drives chronic inflammation associated with aging.
This finding could potentially lead to longer, healthier lives and could help in the prevention of age-related conditions such as deadly heart diseases and brain disorders.
A Malfunction in the Mitochondria
The harmful inflammation is attributed to improper calcium signaling in the mitochondria of certain immune cells, the researchers found.
Mitochondria, the power generators of all cells, rely heavily on calcium signaling.
As we age, mitochondria in immune cells called macrophages lose their ability to absorb and use calcium, leading to chronic inflammation responsible for many age-related ailments.
The researchers, led by Bimal N. Desai, believe that enhancing the calcium uptake by mitochondrial macrophages could prevent this inflammation and its damaging effects.
As macrophages are present in all body organs, including the brain, targeting them with specific drugs could help slow down age-associated neurodegenerative diseases.
Aging and Inflammation: ‘Inflammaging’
Macrophages are white blood cells with crucial roles in the immune system. Their functions include cleaning up dead or dying cells and patrolling for pathogens and other foreign invaders.
While it is known that macrophages become less effective with age, the reasons behind this decline have been unclear until now.
Desai and his team believe they have identified a “keystone” mechanism responsible for age-related changes in macrophages, which renders them prone to chronic, low-grade inflammation.
When these immune cells are confronted by an invader or tissue damage, they become hyperactive, driving what is known as “inflammaging”— chronic inflammation that accelerates aging.
The researchers suspect that this mechanism will not only apply to macrophages but also many other related immune cells generated in the bone marrow.
If true, it could potentially boost our immune systems in old age when we are more susceptible to diseases.
The Road Ahead
Addressing inflammaging will not be as simple as taking a calcium supplement. The problem lies not in a calcium shortage but in the macrophages’ inability to use it correctly.
However, Desai’s discovery has identified the exact molecular machinery involved in this process, so researchers could potentially discover ways to stimulate this machinery in aging cells.
Desai acknowledged the interdisciplinary research effort involved in this discovery, combining computational biology, immunology, cell biology, and biophysics.
Now, the focus is on figuring out the wiring that controls this mitochondrial process in different types of macrophages and then manipulating that wiring creatively for biomedical impact. The findings have been published in the journal Nature Aging.
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The study was published in Nature Aging.
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