What are myokines and how do they protect the brain during resistance training?
Myokines are signaling molecules released by muscles during resistance training that cross the blood-brain barrier and directly benefit the brain. The two most important are irisin, which triggers the expression of BDNF (brain-derived neurotrophic factor) and stimulates the growth of new neurons in the hippocampus, and interleukin-6, which acts as a powerful anti-inflammatory agent during exercise and is also responsible for suppressing tumour cell growth.
What makes myokines so significant is not just their biological role — it's their exclusivity. Pharmaceutical companies are spending billions of dollars trying to replicate these molecules in a pill or injection and have consistently failed. The brain-protective cascade that begins when a muscle contracts under load is, so far, irreproducible outside the body. This is one of the core arguments explored in the episode, drawing on the SMART trial, which demonstrated that resistance training two to three times per week in people already experiencing mild cognitive impairment not only preserved their cognitive function but actively enhanced processing speed, fluid intelligence, and slowed grey matter loss.
The practical implication is direct: the weight room functions as a molecular pharmacy that no lab has been able to match. You can hear the full conversation, including why Bartlett describes leg strength as "by far the most important tool in your toolbox," on The Diary Of A CEO on Listenly.
"Having strong legs is by far the most important tool in your toolbox for the prevention of Alzheimer's disease."
— Steven Bartlett, The Diary Of A CEOSee also
A study on identical twins with the exact same genetic profile, tracked over a 10-year period with cognitive tests and MRIs, found that the twin with the stronger legs showed meaningfully better cognitive outcomes, pointing to leg strength as a key protective factor against Alzheimer's disease.
The ApoE4 gene (Apolipoprotein E gene) is one of the strongest genetic risk factors for Alzheimer's disease. One copy raises risk by two to three times for males and up to six-fold for females — but carrying it is not a foregone conclusion.
The SMART trial took a group of people with mild cognitive impairment and gave them resistance training two to three times per week. They not only preserved their cognitive functions but also enhanced processing speed, fluid intelligence, and showed a measurable slowing of grey matter loss.