The march of time can be cruel to the human body, but new research points to a cause – and possible solution – for some of the diseases and decline that often come with age.
Scientists have long known that cognitive decline as we age and that specific age-related illnesses, including Alzheimer’s, are linked to inflammation, but are still finding out exactly why and how it occurs.
Research published on Wednesday in the journal Nature points to the role of a messenger hormone found at much higher levels in older people and mice than their younger counterparts.
When the hormone was blocked in older mice, they performed as well as younger rodents in memory and navigation tests.
The researchers found that higher levels of the hormone affected the metabolism of immune cells called macrophages, causing them to store energy instead of consuming it.
This effectively leaves the starvation cells and sends them into a harmful inflammatory hyperdrive that contributes to age-related cognitive decline and various age-related illnesses.
The hormone prostaglandin E2 (PGE2) “is an important regulator of all types of inflammation, both good and bad, and its effect depends on the receptor that is activated,” the study’s senior author, Katrin Andreasson, told AFP.
“In this study, we identified the EP2 receptor … as the receptor that leads to energy depletion and maladaptive inflammation,” added Andreasson, professor of neurology at Stanford University.
Having isolated the role played by PGE2, Andreasson and his team began to see if there was a way to counteract its negative effects.
They administered rats two experimental compounds that can block the EP2 receptor and found that they reversed the metabolic problems seen in older macrophages – restoring their younger behavior and preventing destructive inflammatory activity.
They found similar effects in mice that were genetically modified with EP2 receptor deletions.
Older mice that received the compounds or had the receptor deleted from their genes performed as well as young mice when tested for navigation and spatial memory, which deteriorate with aging and diseases like Alzheimer’s.
“Our study suggests that the development of maladaptive inflammation and cognitive decline in aging may not be a static or permanent condition, but that it can be reversed,” says the study.
Andreasson said the findings, while still preliminary, could have implications for a wide range of conditions.
“This applies to most age-related inflammatory diseases,” she told AFP.
“There are many of them, for example atherosclerosis … metabolic syndrome, frailty, arthritis, Alzheimer’s disease,” she added, saying that she is “very excited” about the possible applications.
But the research is still in its early stages and there are several unanswered questions. It is not yet clear how much PGE2 is too much and how it accumulates throughout life.
And none of the experimental compounds have been tested on humans, so it is unclear whether they can be toxic, although no harmful side effects have been seen in the mice tested.
Andreasson said his team is now working on several issues raised by the research, including a more complete understanding of the mechanisms that produce cognitive decline and investigating the role of cell metabolism functions in aging.
© 2021 AFP