Scientists may have discovered how to reverse aging in the brain – BGR

• A Stanford team has figured out how to reverse brain aging and restore mental acuity, a breakthrough that could one day lead to drugs that treat medical problems and cognitive decline.
• The researchers found a way to block the inflammation responsible for the cognitive decline that comes with age.
• Using tailor-made drugs to block the link between a specific hormone and a receptor, the researchers restored the normal function of immune cells that go crazy with age.
• They observed that mice treated with the drug regained memory and spatial orientation skills, performing as well as younger animals in similar tests.

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The aging process is a risk factor in most medical conditions. The older your body and mind, the more difficult it is to do most things, including fighting an infection like the new coronavirus. But several teams of researchers are looking for ways to slow aging, reverse aging or age some organs. In the latter category are Stanford researchers, who may have figured out how to reverse brain aging.

It turns out that the immune system is to blame, at least in part, for aging brain. The scientists found a process to reverse mental aging in mice, and the experiments also worked on human cells in laboratory tests. However, these are just the first steps in creating drugs that could one day be used to prevent medical conditions associated with cognitive decline.

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Dr. Katrin Andreasson’s team published a study in Nature describing his initial work to reduce brain aging. Like Stanford Medicine he explains, biologists have long theorized that inflammation may be responsible for the aging process. Reducing it can delay the onset of certain conditions, such as loss of mental acuity, or even prevent the conditions altogether. Andreasson’s team may have discovered what causes some immune cells to favor inflammatory processes within the body and how to prevent them.

The team found that a type of immune cell called myeloid cells (like macrophages) overdrives as they age, causing inflammation within the tissues, including the brain. Myeloid cells must clean up debris, supply nutrients to other cells and monitor pathogens. But as they get older, they start to misbehave and it damages nearby tissue.

The researchers found that blocking the interaction of a specific hormone (PGE2) and a receptor (EP2) is sufficient to “restore juvenile metabolism and the placid temperament of human and mouse myeloid cells in a dish and in live mice”. The experimental drugs were able to reverse cognitive decline in rats, restoring memory and navigation skills to levels comparable to those of young rats.

“If you adjust the immune system, you can age the brain,” said Andreasson Stanford Medicine.

The problem with the PGE2-EP2 link is “a double hit”. Myeloid cells, like macrophages, produce more PGE2 than younger cells and have more EP2 receptors on their surfaces. This leads to an increase in the processes that lead to local inflammation. EP2 is found in immune cells, including myeloid cells, and can initiate inflammatory activity inside cells after binding to PGE2.

Andreasson’s team tried two experimental drugs that blocked the PGE2-EP2 link. This caused the aging myeloid cells to behave like the younger versions, reversing their inflammatory activities in laboratory tests with incubated mice and human macrophages. As for live mice, the older individuals who received the drugs performed as well on tests of memory and spatial navigation as the younger mice, and the indication that the drugs can age the brain. One of the drugs was effective, although it did not penetrate the blood-brain barrier.

While this research looks promising, the team is far from conducting clinical trials for drugs that can slow or reverse conditions like dementia or Alzheimer’s. Andreasson said neither of the two drugs being tested could be used in humans, citing potential toxic side effects. But the study may lead to different compounds that may be safe for testing in humans in the future and may eventually help prevent cognitive decline after a certain age.

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