Researchers have found a way to slow down the aging process by reducing chronic inflammation that plagues older tissues. As we age, our bodies accumulate the cellular equivalent of clutter, much of which is made up of the remains of neutrophils, the most abundant white blood cells in the immune system.
Neutrophils are plentiful because they have an important job — clearing pathogens like bacteria and viruses from the body. In general, neutrophils don’t stick around for very long, though. After 12 to 24 hours, most are cleared through the liver, spleen and bone marrow.
Clearing out any remaining neutrophils is important because when they become old and stick around they become toxic, injuring nearby cells and eventually contributing to inflammation in organs and tissues. This inflammation is one of the hallmarks of aging.
Katrin Andreasson told the outlet that the clearing of senescent neutrophils is important for preventing chronic inflammation. They have been trying to figure out why we age. Now they know one big reason for it.
The job of clearing neutrophils falls to immune cells called macrophages, including a type of macrophage found in every organ of the body. The body normally clears these aging neutrophils, but when prostaglandins, lipids with hormone-like actions that the body makes primarily at sites of tissue damage or infection, bind to certain receptors on the surface of these macrophages, it interferes with their ability to clear old, senescent neutrophils and causes inflammation.
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To prevent this from happening and improve the removal of senescent neutrophils and reduce the effects of aging, researchers at Stanford University and the University of Münster in Germany developed a mouse model in which the gene that codes for the prostaglandin receptor on macrophages, EP2, was deleted.
The deletion prevented conditions such as heart disease and fat accumulation that are both driven by chronic inflammation and common in old age. Deleting the gene also slowed cognitive decline. The results made it clear that chronic inflammation plays an important role in these conditions and in the aging process.
The study compared younger normal mice and older normal mice to other older mice who were identical except the gene for EP2 had been deleted when they were four to six months old. They found that the deletion of the EP2 gene rebooted the destruction of old neutrophils prevented by the binding of a prostaglandin to the EP2 receptor.
As a result, worn-out, senescent neutrophils accumulated in the livers, spleens, bone marrow and other organs of older normal mice, but not in the organs of older mice lacking the EP2 gene.
The researchers found that levels of 71 proteins in the blood were significantly changed in older normal mice compared to younger normal mice. Many of those proteins are produced in the liver.
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Deletion of the EP2 gene reduced inflammation in the blood, liver, colon, heart and kidneys of older mice. It also reduced inflammation in the hippocampus, the part of the brain responsible for memory and navigation ability.
Older mice lacking the EP2 gene could handle a maze and recall objects they had seen before almost as well as younger mice.
Their speed, balance and forelimb grip strength were like those of younger mice. When the researchers treated normal 22-month-old mice with an experimental drug that inhibited EP2, they found it reduced total and senescent neutrophil levels to levels similar to those of younger mice.
These findings suggest a drug that blocks EP2 on tissue-resident macrophages could slow the aging process. No currently approved drugs block just the EP2 receptor, however, although several target the prostaglandin, Katrin Andreasson said. Nonsteroidal anti-inflammatory drugs, or NSAIDs, for example, block the production of the prostaglandin that connects to the EP2 receptor, affecting patient costs.
The study is published in a scientific journal.
