To ensure that this reaction was not purely rodent-based, the scientists also checked blood drawn from elderly people. The older men and women who habitually walked for exercise showed higher levels of GPLD1 in their bloodstreams than those who did not.
The combined upshot of these findings seems to be that exercise improves brain health in part by prompting the liver to pump out extra amounts of GPLD1, Dr. Villeda says, although it is not yet clear how the protein then changes the brain. Subsequent experiments by the scientists showed that the protein probably does not breach the blood-brain barrier and act directly on the brain, Dr. Villeda says. Instead, it is likely to incite alterations in other tissues and cells elsewhere in the body. These tissues, in turn, produce yet more proteins that have effects on other tissues that eventually lead to direct changes to the neurotransmitters, genes and cells in the brain itself that undergird cognitive improvements.
Dr. Villeda believes that if further experiments show that GPLD1, in isolation, helps to initiate this molecular chain reaction, then it is at least conceivable that infusions of the substance might offer the brain benefits of exercise to people who are too frail or disabled for regular physical activity.
This experiment principally involved mice, though, not people, and does not tell us anything about the systemic effects of extra GPLD1, which in high amounts might be undesirable. More fundamentally, the findings highlight the pervasive, intricate, whole-body effects of exercise, with the liver, in this case, somehow changing minds and brains after workouts. At the moment, it is impossible to know if the same synchronized, interwoven processes all would occur in response to a GPLD1 exercise pill and, if not, whether it could be considered an exercise pill at all.
Dr. Villeda is quick to agree that pharmaceutical GPLD1, even if effective for brain health, “would not recapitulate the benefits of exercise.” There would be none of the usual fat burning, muscle building or cardiovascular improvements, he points out. But he hopes that, if future experiments in his lab with animals and people show consistent results, the substance might eventually help people who find moving difficult to think better.