When Immune Cells Malfunction
Myeloid cells are special immune cells found in the brain, circulatory system and peripheral tissue. They not only help to fend off infection, but also clear away debris. However, as our bodies age, these cells malfunction and are unable to carry out these tasks effectively. Myeloid cells are also the body's main source of the hormone-like molecule prostaglandin E2 (PGE2) which can promote inflammation. One particular receptor for PGE2 is found in abundance on myeloid cells. It's called EP2. When PGE2 docks with EP2 it triggers inflammation inside the cells. The researchers wanted to confirm if this happens more in older people. So, they cultured macrophages, a class of myeloid cells, and microglia, a type of macrophage that's found in the brain, from people over age 65, and compared those cell cultures to cultures from those under age 35. They did the same for old and young mice. The Stanford scientists discovered that, in both mice and humans, not only is much more PGE2 produced in the older cells, but there were far higher numbers of EP2 receptors on the cells’ surfaces. What’s more, in the blood and brains of elderly rodents they found much higher levels of PGE2 than they did in the blood and brains of the younger mice. Lead scientist Katrin Andreasson described the higher numbers of both the hormone and its receptor as "a double whammy - a positive feedback loop" that ramps up intracellular processes linked to inflammation in the macrophages.How Inflammaging Happens
This damaging process begins with glucose, or sugar. Vastly higher PGE2-EP2 docking in older cells diverts glucose into storage instead of towards the production of energy. And it’s this chronic state of energy depletion that prevents normal cellular function and stokes the fires of inflammation. But what would happen when the Stanford team blocked the receptor so PGE2 can't attach to EP2 in older cells? In both mouse and human myeloid laboratory cell cultures, researchers found improved glucose metabolism—as strong as in the young myeloid cells— and a signifncant drop in inflammation. The big question now was whether this restoration of youthful metabolism could be replicated in mice, and if so, how would this affect their memories?Turning Back the Clock for Mouse Memories
Stanford researchers used a group of mice that were genetically modified from birth to remove the EP2 receptor in both macrophages and microglia. Then, they gave a drug to normal mice that only turns off the receptor in macrophages outside the brain. The startling result was that under both conditions, old mice given navigation tests and object recognition tests to assess learning and memory performed just as well as their young counterparts. Even more exciting, in the healthy elderly mice, age-related cognitive decline was reversed. This fascinating finding means that even resetting myeloid cells outside the brain can have profound effects inside the brain. Dr. Andreasson described the changes caused by PGE2-EP2 binding as a powerful pathway that drives aging but "it can be downshifted. If you adjust the immune system, you can de-age the brain," the neuroscientist said.Lowering PGE2 with Food
She also believes their findings have implications for most age-associated inflammatory diseases. "There are many of these, for example atherosclerosis...metabolic syndrome, frailty, arthritis, Alzheimer's" she added, saying she is "very excited" about the discovery’s potential. However, it could be many years before a treatment becomes available for people. In the meantime, Dr. Andreasson’s findings emphasize the importance of eating a diet containing plenty of inflammation-lowering compounds that are found particularly in colorful fruits and vegetables. Some of these have even been shown to block PGE2 at the cellular level. Examples include resveratrol from grapes, red wine, blueberries, cranberries, and dark chocolate; quercetin, found in apples, raspberries, onions, red grapes, cherries, citrus fruits, and green leafy vegetables; and fisetin found in strawberries. In other words, eat a diet rich in colorful fruits and vegetables to fight inflammation, while avoiding inflammatory foods such as refined sugar or anything processed or fried. There are also a wide variety of supplements available to help lower inflammation. Dr. Andreasson and her team of neurocscientists published their findings in the journal Nature in January.