Exercise is the most underrated and under-utilised DMT. Why?
Ever since I ditched football, or soccer as it is called in the Americas, as a skinny 13-year old for long-distance running I knew intuitively that there was something extraordinary about aerobic exercise. Running is not only mindfulness, but it makes you think clearer in general and lifts your mood. Long-distance running is a philosophy and it adds true meaning to life. For those of you who are exercise-junkies, you will know what I am talking about. For those of you who haven’t experienced the uplifting benefits of exercise, I would suggest reading Haruki Murakami’s book ‘What I Talk About When I Talk About Running’. Murakami is an extraordinary writer and brings a wonderful and mystical Japanese philosophical twist to the task at hand.
It is clear that running or exercise, in general, is one of the most underutilised treatments we have for multiple sclerosis and neurodegeneration in general. It is clear that exercise and diet have to be at the base of any brain health pyramid. As always there is biology that underpins the treatment effects of these simple lifestyle interventions. Most of us have assumed exercise works by simply stimulating growth factors and endorphins in the central nervous system. Growth factors are responsible for anti-ageing effects and endorphins for its mood-elevating effects and explain the runner’s high. However, the latest work just published in Science (see below) shows that the health benefits of exercise on ageing may be mediated by a hormone that is released from the liver.
The circulating factor is glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), which increases after exercise and was shown to correlate with improved cognitive function in aged mice. Importantly blood levels of Gpld1 are increased in active healthy elderly humans. If this work is confirmed it means we may be able to hack exercise’s effects on this pathway and create a drug that you can take that will prevent you from ageing and if you have MS slow down your disease progression. Wouldn’t that be a remarkable innovation?
As always to create a viable market for anti-ageing drugs we need to classify ageing as a disease. This will create the incentive for Big Pharma to invest. If we don’t classify ageing as a disease antiageing medications will be confined to the consumer market, which makes it very difficult to study in diseases such as MS and get them licensed by the regulatory authorities as treatments for multiple sclerosis and other neurodegenerative diseases. If you interested in reading more on this issue please read my Medium post from three years ago where I make the case that ageing is a disease.
Horowitz et al. Blood Factors Transfer Beneficial Effects of Exercise on Neurogenesis and Cognition to the Aged Brain. Science. 2020 Jul 10;369(6500):167-173. doi: 10.1126/science.aaw2622.
Reversing brain aging may be possible through systemic interventions such as exercise. We found that administration of circulating blood factors in plasma from exercised aged mice transferred the effects of exercise on adult neurogenesis and cognition to sedentary aged mice. Plasma concentrations of glycosylphosphatidylinositol (GPI)-specific phospholipase D1 (Gpld1), a GPI-degrading enzyme derived from liver, were found to increase after exercise and to correlate with improved cognitive function in aged mice, and concentrations of Gpld1 in blood were increased in active, healthy elderly humans. Increasing systemic concentrations of Gpld1 in aged mice ameliorated age-related regenerative and cognitive impairments by altering signaling cascades downstream of GPI-anchored substrate cleavage. We thus identify a liver-to-brain axis by which blood factors can transfer the benefits of exercise in old age.
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