Age-related cognitive decline reversed in mice by fighting inflammation in the brain

As mammals age, inflammation levels increase. I’m not talking about painful reactions to wound or infection, but rather a more low-key, grinding, background inflammation that grows increasingly intense the longer we live. This growing inflammation has been associated with diabetes, high blood pressure, frailty, cancer, and just about every chronic health problem we tend to see in old age. This also includes cognitive decline and, at least in this case, scientists believe that it can be reversed through managing inflammation in the brain, as studies on mice have shown.

Researchers at the University of Brighton in the UK found that microglia — a specialized population of macrophage-like cells in the central nervous system, which act as immune cells that defend the brain and spinal cord from foreign invaders — are very vulnerable to changes in the levels of inflammation, particularly to a molecule called  prostaglandin E2(PGE2).

When this molecule was in high amounts, the microglia had trouble carrying out their normal cellular processes and related cells didn’t generate energy as well as they could.

Levels of PGE2 naturally increase with age in our cells and those of other mammals due to the growing number of senescent cells. These dysfunctional cells cannot divide anymore and their presence causes the release of PGE2, as well as other inflammatory molecules.

But there’s a way to reverse this process. Writing in the journal Nature, scientists described how PGE2 exerts its effects on cells by interacting with the EP2 receptor on the macrophages, another important type of white blood cell.

When these white blood cells were treated in the lab with drugs that turned this receptor off, the cells recovered. Moving away from the petri dish, the researchers replicated the experiment on mice.

The researchers genetically modified rodents that lacked the EP2 receptor and simply waited for them to grow old (the average lifespan of a mouse kept in captivity is two years). They then tested the cognitive abilities of these elderly mice by subjecting them to a barrage of tests, including navigating mazes and “object location” tasks.

Strikingly, the researchers found that the old genetically modified mice could learn and remember things just as well as their young counterparts. The same effects were replicated in old, normal mice that weren’t genetically modified but which received drugs that turn the EP2 receptor on or off.

Essentially, this series of experiments shows that suppressing the PGE2 receptor may represent an important target for treating and maybe even reversing age-related cognitive disorders. Or at least that seems to be the case in mice. Clinical trials in the future on humans may shed more light.

In the meantime, research has shown that foods such as blueberries, strawberries, and spinach improve cognition in both older mice and people. These foods are rich in fisetin, quercetin, and resveratrol, which are known to flush senescent cells out of the body. One possible mechanism by which they may achieve this is by blocking PGE2 at the cellular level. So until more research can offer more straightforward answers, stock up on that spinach.


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