Physiology Friday #114: "Exercise Transplant" Improves Brain Health
Sedentary mice who were given an infusion of blood from exercise-trained mice experienced dramatics improvements in cognitive performance, suggesting that the benefits of exercise may be transferable.
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We all know that exercise is great for both body and brain, mind and soul. A prerequisite for a healthy lifespan seems to involve at least a minimal amount of physical activity. You know the saying: “a body in motion stays in motion.”
Exercise might become more important as we age — especially for the brain. Age-related cognitive decline, dementia, and Alzheimer’s disease are all concerns for elderly individuals. Exercise seems to be one way to offset the negative effects of time on the brain. In animals, exercise has been shown to prevent neurodegeneration and even reverse some of the impairments in cognition, learning, and memory that occur with age.
The problem is — most people don’t exercise enough. Some people enjoy it, some people need it, but others despise it. The fact is, a large majority of our population doesn’t even meet the minimum physical activity requirements. While this has an uncontroversial impact on metabolic health, there’s a good chance that sedentary lifestyles contribute to the “epidemics” of cognitive decline and unhealthy aging.
This brings up the much-debated but enticing topic of an “exercise pill.” What if we could “bottle up” the benefits of exercise and take it as a supplement. We could save time, money, and energy, all while reaping the benefits of a long hard run or a vigorous session in the weight room. An exercise supplement could be given like a medicine to older people who can't exercise or individuals with certain debilitating diseases.
Since exercise upregulates literally thousands of genes in our body, it’s unlikely we will find a “pill” that fully encapsulates every single benefit of activity. You just can’t perfectly mimic the integrative effects of exercise without actually going out and breaking a sweat. Sorry to burst your bubble.
But, as a new study shows, there are specific aspects of exercise that we could potentially harness into a pill or elixir, allowing us to transfer the benefits to non-exercising organisms. Specifically, it might be possible to get the brain-boosting power of exercise by receiving an exercise “transplant” from a friendly, fit donor.
Published in the journal Science, the study had the aim of testing whether exercise-induced circulating factors in the blood could transmit the beneficial effects of exercise on brain regeneration and cognition in old mice.
Brief study overview
In the first set of experiments, two groups of mice were studied: one group was allowed 24/7 access to a running wheel, and the other group was allowed to be sedentary. The exercised and sedentary mice were compared to each other and compared to young mice to assess the levels of cognitive impairment that occur with age, and how exercise might affect this process.
To test whether the benefits of exercise on brain aging could be transferred through blood plasma, old sedentary mice were injected with plasma from the old exercised mice for 3 weeks. Old mice were also injected with plasma from mature (not old) mice who exercised. The purpose here was to see if the age of the mice made a difference in the effects of plasma transfer.
A set of experiments in this study determined that a specific factor known as GPLD1 was primarily responsible for some of the beneficial effects of exercise on the brain. Old exercised mice (and healthy elderly humans) had higher levels of GPLD1 compared to sedentary animals and humans.
So next, the goal was to determine if simply providing GPLD1 could recapitulate the benefits of exercise on the brain. Aged sedentary mice were injected with gene expression constructs for GPLD1, which would “artificially” increase levels of this molecule in their circulation (mainly the liver).
Unsurprisingly, the old mice who exercised had increased levels of neuron growth (neurogenesis), increased levels of a beneficial brain compound called brain-derived neurotrophic factor (BDNF), and better learning and memory performance compared to old sedentary mice.
In old mice given plasma from old exercised mice, higher levels of neuron growth were observed along with greater BDNF expression.
Higher levels of neuron growth in mice given exercised plasma (Run) vs. sedentary (Sed) mice
What about cognitive performance? Old sedentary mice who got the exercised plasma performed better on tests of learning and memory when compared to sedentary mice.
It didn’t matter whether the plasma came from mature or old exercised mice — both were beneficial.
When GPLD1 was overexpressed in the liver of old sedentary (non-exercised) mice, they too showed increased levels of neurogenesis, BDNF, and higher levels of cognitive performance when compared to their sedentary peers who didn’t receive the GPLD1. This suggests that GPLD1 alone is sufficient to cause many of the brain-enhancing effects of exercise in mice.
Overexpressing GPLD1 in mice enhanced neurogenesis and led to better cognitive performance compared to controls
Thoughts and musings
The novel findings of this study were not that exercise improves brain health and function with age — this was well established. What the research uncovers is that you can take plasma from exercised animals, give it to sedentary animals, and the sedentary animals can reap the rewards.
Now — this study only measured a few aspects of cognitive structure and function. We can’t conclude that the sedentary mice received ALL of the benefits of exercise on their physiology; they likely did not.
However, at least in terms of neurogenesis and “rescuing” the mice from cognitive decline, the plasma swap was effective.
Furthermore, it turns out that you don’t even need whole blood plasma for the “exercise transplant” to work effectively — GPLD1 alone will do the trick. That’s pretty remarkable — that one little molecule (likely with many downstream signaling cascades) can provide so many benefits.
As our population ages and cognitive disorders become prevalent, strategies targeted to the brain seem worthwhile. Even more interesting is that perhaps we could use GPLD1 as a "cognitive enhancer" for healthy people.
Will we bottle up GPLD1 and start giving it out to everyone like a vitamin? Probably not. But, this research just adds to the growing body of evidence that the benefits of exercise are transmitted through thousands of molecules, some of which we can identify and potential use as therapeutic strategies.
If an exercise pill existed, would you take it? I’d love to hear your thoughts in the comments below.
Until next Friday,