Scientists Think Flipping a Single Switch in Your Body Could Slow Down Aging

3 min readHere’s what you’ll learn when you read this story:A new study shows how aging immune cells fail to clear dead white blood cells, driving inflammation and aging. The researchers identified a receptor called EP2 that builds up on aging macrophages, blunting their ability to clear senescent neutrophils, the body’s most common white blood cell.When the EP2 gene was removed from mice, scientists noticed that dozens of blood proteins were younger than those in mice without any genetic alteration.The biological world is filled with threats. While our ancient hominid ancestors lived dangerous lives nestled well below the top of the food chain, they also had to contend with bacteria, viruses, and other dangerous pathogens that could kill in equal measure. Thankfully, hundreds of millions of years of evolution honed our modern immune system, an impressive defensive mechanism where cells, tissues, and organs work together to fend off microbial menaces.However, no defensive strategy is completely perfect, and while human ingenuity has plugged gaps in our defense with antibiotics and vaccines, degradation of the immune system itself could be a key driver of human aging. At least, that’s the conclusion of a new Science study on tissue-resident macrophages, the immune cells that live inside our organs. When they falter with age, dead neutrophils build up in the blood and tissues instead of being cleared away.“Senescent neutrophils are killing our tissues,” Stanford’s Katrin Andreasson, senior author of the study, said in a press statement. “Clearance of these cells is essential for preventing chronic inflammation.”To understand this aging mechanism requires a brief trip down the microbial nesting doll that is the human immune system. Neutrophils are the body’s first line of defense against infection and they’re designed for combat, living only a day at most. Although white blood cells account for only one percent of your total blood volume, the body produces roughly 100 billion of them a day. And all those cells also need to be cleared or they’ll become dysfunctional and cause harmful inflammation. This clean-up job is the work of macrophages, including tissue-resident macrophages that live inside organs.It’s these organ-based macrophages that interest the researchers, because they also make hormones called prostaglandins. One of these hormones, known simply as PGE2, also has a receptor called EP2 that promotes inflammation. As these tissue-resident macrophages age, concentrations of EP2s also rise, preventing the macrophages from carrying out their primary role of clearing neutrophils. Suddenly, you have a teetering domino effect that disrupts the entire system, leading to aging and eventually, death. Aging macrophages produce excess EP2, causing senescent neutrophils to accumulate in the bloodstream and tissues, inducing the inflammation and cellular damage that humans experience as aging.To better understand this mechanism, scientists engineered a population of mice—some younger and some older—without the EP2 gene, and then compared them to unaltered mice of similar age. When the researchers compared the two sets of older mice, the difference was stark. Age had altered 71 blood proteins in the normal animals, but in the EP2-free mice, 59 of those proteins still looked young, and a striking number of them came from the liver. Signs of neutrophil senescence were lower, too.“The liver is one of the body’s most tissue-resident-macrophage-enriched organs and a major contributor to aging-related changes in blood chemistry,” Andreasson said in a press statement. “It’s the central organ determining the body’s metabolic rate.”The researchers also pored over a database containing information about different cell types in diseased human livers and found similar trends also present in the mice-based experiments. Unfortunately, it isn’t simple to design a drug that targets EP2 directly, though many pain medications currently target PGE2. Removing PGE2 entirely isn’t an option because that hormone has other benefits when interacting with different receptors. So the next step will be to somehow find a way to target EP2 while leaving the hormone’s other functions intact.“We’ve been trying to figure out why we age,” Andreasson said in a press statement. “Now we know at least one big reason for it.”Darren lives in Portland, has a cat, and writes/edits about sci-fi and how our world works. You can find his previous stuff at Gizmodo and Paste if you look hard enough.