Suppose Smokey Bear were to lose it and start setting forest fires instead of putting them out. That roughly describes the behavior of certain cells of our immune system that become increasingly irascible as we grow older. Instead of stamping out embers, they stoke the flames of chronic inflammation.
Biologists have long theorized that reducing this inflammation could slow the aging process and delay the onset of age-associated conditions, such as heart disease, Alzheimer’s disease, cancer, and frailty, and perhaps even forestall the gradual loss of mental acuity that happens to nearly everyone.
Yet the question of what, exactly, causes particular cells of the immune system to kick into inflammatory overdrive has lacked a definitive answer.
Now, Stanford Medicine researchers think they have one. If their findings in old mice and in human cell cultures apply to actual humans, they could presage the pharmaceutically managed recovery of older people’s mental abilities.
In a study published Jan. 21 in Nature, the investigators pin the blame on a set of immune cells called myeloid cells. Katrin Andreasson, MD, professor of neurology and neurological sciences, is the study’s senior author. Its lead author is MD-PhD student Paras Minhas.
Myeloid cells, which are found in the brain, the circulatory system and the body’s peripheral tissues, are part soldier and part park ranger. When not fighting off infectious intruders, they keep busy cleaning up debris, such as dead cells and clumps of aggregated proteins; provide nutrient snacks to other cells; and serve as sentinels watching for signs of invading pathogens.
But as we age, myeloid cells begin neglecting their normal, health-protecting functions and adopting an agenda of endless warfare with a nonexistent enemy, inflicting collateral damage to innocent tissues in the process.
In the study, blocking the interaction of a particular hormone and a receptor that abounds on myeloid cells was enough to restore the youthful metabolism and placid temperament of mouse and human myeloid cells in a dish and in living mice. This blockade also reversed age-related mental decline in older mice, restoring their recall and navigation skills to those exhibited by young mice.
“If you adjust the immune system, you can de-age the brain,” Andreasson said. Her team’s experiments in human cells suggest that similar rejuvenation may be possible in people, she said.
Myeloid cells are the body’s main source of PGE2, a hormone that belongs to the family known as prostaglandins. PGE2 does many different things in the body — some good, some not always so good — for example, promoting inflammation. What PGE2 does depends on which cells, and which of several different varieties of receptor on those cells’ surfaces, the hormone lands on.
One receptor type for PGE2 is EP2. This receptor is found on immune cells and is especially abundant on myeloid cells. It initiates inflammatory activity inside the cells after binding to PGE2.