The Brain-Boosting Properties of Runner’s Blood

Whenever I donate blood, I like to imagine the lucky recipient suddenly perking up, feeling the vivifying effects of my runner’s hemoglobin-rich red blood cells. “Whoa, that’s the good stuff,” I imagine this hypothetical person exclaiming. (Hey, it gets me off the couch and to the donation center.)

Turns out I’ve been underselling myself, according to a cool new study that injects “runner plasma” from exercising mice into sedentary mice and sees a range of remarkable brain-boosting effects, including better memory and reduced inflammation. The study, published in Nature by researchers in the lab of Stanford University neurologist Tony Wyss-Coray, offers some exciting new insights about how and why exercise is good for the brain. It has also generated some media coverage along a predictable theme: “An exercise pill might one day produce health gains without the exertional pain,” as Scientific American puts it. Maybe so—but only in a very limited way.

The details of the study are described in a detailed press release from Stanford. The key part of the experiment involved letting a group of mice run four to six miles every night on an exercise wheel for a month, while another group lived in similar cages but with the exercise wheel locked. Then they injected a third group of mice with plasma from either the runners or the sedentary group, and put them through a bunch of tests.

Sure enough, the mice that received runner plasma were—and this is Wyss-Coray’s word—“smarter.” They did better on tests of memory and cognition, for example finding a submerged platform in a pool of opaque water. They also had less inflammation in the brain, which is important since brain inflammation is associated with the progression of diseases like Alzheimer’s. A series of elegant experiments suggested that a protein called clusterin was responsible for most of this effect.

An obvious point to consider is that results in mice don’t necessarily transfer to humans. The Stanford paper does include a human component: 20 older adults with mild cognitive impairment did a mix of aerobic and resistance exercise three times a week for six months. At the end of the program, they had more clusterin in their blood, and also did better on memory tests. That’s not proof, but it does bolster the case for believing these results are relevant.

The tougher question is what these findings might portend. The press release ends like this: “Wyss-Coray speculated that a drug that enhances or mimics clusterin… might help slow the course of neuroinflammation-associated neurodegenerative diseases such as Alzheimer’s.” That’s the goal that motivated this research, and as someone whose family has been impacted by Alzheimer’s I’m really hoping it pans out, and quickly.

But as for the more general hopes of a pill that reproduces the benefits of exercise without breaking a sweat, it’s worth looking back at some earlier research. For example, last year a team from the University of California San Francisco led by Saul Villeda, a former postdoc in Wyss-Coray’s lab, published a similar experiment in which plasma from exercised mice improved brain function and triggered the formation of new brain cells in older sedentary mice—but identified a different molecule called glycosylphosphatidylinositol-specific phospholipase D1 as the active ingredient. In other words, there isn’t just one magic exercise molecule that affects your brain. And there probably aren’t just two, either.

Back in 2009, Frank Booth and Matt Laye, then at the University of Missouri, wrote an article in the Journal of Physiology decrying the rise of research into (and publicity for) “exercise mimetics,” which is another way of saying “exercise in a pill.” At the time they were reacting to a spate of publicity about research from the Salk Institute for Biological Studies into a drug called AICAR (a line of research that is still ongoing today). But Booth and Laye didn’t buy it. For one thing, they pointed out, exercise has hundreds of demonstrated biological effects in pretty much every organ system in the body: “circulatory, neural, endocrine, skeletal muscle, connective tissue (bones, ligaments and tendons), gastrointestinal, immune and kidney.” No single pill could possibly mimic all those effects.

Even if you’re only interested in one specific organ, it’s hard to isolate the source of exercise’s benefits. Clusterin, from Wyss-Coray’s study, is likely produced in the liver and heart then affects the brain. The molecule in Villeda’s study also comes from the liver. Exercise is a full-body therapy whose impact in one place depends on responses in other places.

Booth and Laye have more general critiques of the pursuit of a pharmaceutical alternative to exercise, mostly notably its cost compared to spending more effort getting people to do exercise. There are some important counterarguments to their paper. Some people can’t exercise; others, it seems increasingly clear, won’t. And even if they do, exercise on its own can’t fully prevent or halt the progression of diseases such as Alzheimer’s. So I’m fully supportive of Wyss-Coray’s research—both for pragmatic reasons, and simply because it offers fascinating new insight into how the body works.

I do think it needs to be kept in context, though. We may eventually get a new drug for Alzheimer’s, though the odds of this particular molecule leading to success—like the odds of your precociously speedy toddler eventually setting a world record—are very, very long. But we’re never going to get a drug that truly replaces all the benefits of exercise, and we should stop pretending it’s even theoretically possible.

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