Can immune cells cure the “aging” of the brain?

Researchers have identified important factors in mental aging.

They also showed that by modifying the glitches of soldiers at the forefront of the immune system, it could be prevented or reversed.

Certain cells of our immune system become more and more unstable as we grow older. Instead of punching out the embers, they stir up the flames of chronic inflammation.

Biologists have long argued that reducing this inflammation slows down the aging process and can delay the onset of age-related conditions such as heart disease. Alzheimer’s diseasePrevents the gradual loss of mental acuity that occurs in cancer, frailty, and perhaps almost everyone.

But to be precise, the question of what causes certain cells of the immune system to initiate inflammatory overdrive lacks a definitive answer.

Now researchers think they have it. If the findings in aged mice and human cell cultures apply to real humans, they can predict the recovery of the psychological capacity of the pharmaceutically controlled elderly.

In a new study of Nature, Researchers hold responsibility for a set of immune cells called bone marrow cells.

The bone marrow cells found in the brain, circulatory system, and peripheral tissues of the body are partly soldiers and partly park rangers. When they do not repel infectious invaders, they are busy cleaning up debris such as dead cells and aggregated protein clumps. Provides nutritional snacks to other cells. It acts as a sentry to monitor for signs of invading pathogens.

But as we grow older, bone marrow cells begin to ignore normal health protection functions, adopt the agenda of endless warfare with non-existent enemies, and in the process cause incidental damage to innocent tissues. ..

Reverse aging of the brain

In this study, blocking the interaction of certain hormones with receptors that are abundant in bone marrow cells restores youthful metabolism and mild temperament of dish and living mouse and human bone marrow cells. It was enough to do.This blockade also reversed age-related stuff Mental decline Older mice revert their recall and navigation skills to those shown by younger mice.

“By adjusting the immune system, the brain can age,” says Katrin Andreason, a senior author who is a professor of neurology and neuroscience at Stanford University. Her team’s experiments with human cells suggest that similar rejuvenation may be possible for people, she says.

Bone marrow cells are the body’s main source of PGE2, a family hormone known as prostaglandins. PGE2 does many things in the body, including promoting inflammation. For example, some are good and some are not always good. What PGE2 does depends on which cell and which of several different types of receptors on the surface of those cells the hormone lands on.

One receptor type for PGE2 is EP2. This receptor is found in immune cells, especially in bone marrow cells. After binding to PGE2, it initiates inflammatory activity inside the cell.

Andreason’s team cultured macrophages, a class of bone marrow cells found in tissues throughout the body of people over the age of 65, and compared them to macrophages in people under the age of 35.

“Double wormy”

They observed that old mouse and human macrophages not only produce much more PGE2 than younger macrophages, but also have much more EP2 on the surface. Andreason and her colleagues also confirmed a significant increase in PGE2 levels in the blood and brain of aged mice.

“It’s a double pain and a positive feedback loop,” says Andreasson. The resulting exponential increase in PGE2-EP2 binding amplifies the intracellular processes associated with inflammation of bone marrow cells.

Researchers have shown how this inflammatory hyperdrive begins in both human and mouse bone marrow cells. Significant increases in PGE2-EP2 binding in the bone marrow cells of the elderly alter these intracellular energy production by rerouting glucose, which promotes intracellular energy production. From consumption to storage.

Researchers have found that bone marrow cells are more likely to be caused by an increase in PGE2-EP2 binding with age, converting this energy source into long glucose chains called glycogen (starch-equivalent animals). Discovered to store glucose. Energy production. Its storage and subsequent chronic energy depletion drive cells into inflammatory anger, causing havoc in aged tissue.

“This powerful pathway accelerates aging,” says Andreason. “And it can shift down.”

Researchers have shown this by blocking hormone receptor responses on the surface of mouse bone marrow cells. They fed mice with one of two compounds known to interfere with PGE2-EP2 binding in animals. They also incubated cultured mouse and human macrophages with these substances. In doing so, the old bone marrow cells metabolized glucose in the same way as the young bone marrow cells, reversing the inflammatory properties of the old cells.

Even more impressive, these compounds reversed the age-related ones in mice. Cognitive decline.. Older mice that received them were tested for recall and spatial navigation, as were young adult mice.

One of the two compounds used by the researchers was effective without crossing the blood-brain barrier. According to Andreason, this suggests that simply resetting bone marrow cells outside the brain can have a significant impact on what is happening inside the brain.

Neither compound has been approved for human use and was not observed in mice, she said, but may have toxic side effects. They provide a roadmap for developing compounds that pharmaceutical companies can give to people.

Additional researchers from Stanford University, Princeton University, and Keio University School of Medicine in Tokyo also contributed to this study.

The work was funded by the National Institutes of Health, the American Heart Association, Bright Focus, the Soros Foundation, Gerald J. Lieberman Fellowship, Howard Hughes Medical Institute Hanna H. Gray Fellow Program, Burroughs Welcome Fund, and Stanford Innovation. .. Fund, Takeda Pharmaceutical Science Frontier Fund, Ludwig Cancer Foundation, Japan Science and Technology Agency, Scully Family Initiative, Taube Family Foundation, Jumperkins Foundation.

Source: Stanford University