The science of how contracting your muscles sends chemical signals that strengthen memory, focus, and long-term brain health.
The Missing Piece in Brain Health
What if the key to sharper memory isn’t in your head—but in your muscles?
Many people know exercise “helps the brain,” but few understand why.
Muscle is more than a tissue that helps move your body from one place to another – rather muscle itself acts as an endocrine organ. Muscle acts as an endogenous communicator sending biochemical messages – known as myokines – to help protect and enhance the brain.
Muscles as an Endocrine Organ
For decades, we thought of muscles as mere “motors” for movement. Modern neuroscience and physiology reveal that they’re also endocrine organs — meaning they release signaling molecules into the bloodstream during contraction.
Our muscles release myokines (Myo- for “muscle” -kine for “to move” or “to set in motion”) which are protein complex’s released from the muscle fiber contractions into the bloodstream. They act as hormones and peptides traveling through the blood to influence distant organs, including the brain.
BDNF (Brain-Derived Neurotrophic Factor)
Not directly produced by muscle but is produced through a myokine-related process
Boosts neuroplasticity, learning, memory, and emotional resilience. Released during muscle contraction; levels spike after resistance and aerobic exercise.
IGF-1
(Insulin-like Growth Factor 1)
Promotes neuronal growth, survival, and synaptic repair. Produced in muscle and liver; transported to the brain post-exercise.
Cathepsin B
Stimulates hippocampal neurogenesis (memory center of the brain). Released after moderate to intense muscular activity.
Irisin
Converts inactive neurons to active ones and supports metabolism and cognition. Formed from FNDC5 during prolonged or intense muscle work.
Lactate
Metabolite, acts like myokine
Fuels neurons and enhances BDNF expression in the brain. Produced by muscles under exertion.
Why Only Muscular Contraction Unlocks These Benefits
When a muscle contracts under tension – whether during lifting, sprinting, or other resistance-based movements – it initiates a cascade of mechanical-to-chemical signaling within the body. These contractions trigger changes in intracellular calcium and metabolic stress, which serve as the key cues for the release of myokines. This process cannot be replicated by sitting, thinking, or taking supplements; only voluntary, repeated muscle contractions activate this sophisticated signaling network. Importantly, muscular effort also demands precise coordination from the brain, creating a dynamic brain-muscle dialogue that enhances synaptic efficiency and stimulates the production of neural growth factors. While low-intensity activity offers some benefit, it is moderate-to-high effort – such as lifting challenging weights or performing interval training – that maximizes the release of critical molecules like BDNF, IGF-1, and irisin, providing the most potent stimulus for cognitive and memory enhancement.
How Myokines Improve Memory and Cognition
Stimulating Neurogenesis: Myokines released during muscle contraction encourage the hippocampus – the brain’s memory hub – to generate new neurons, enhancing learning and recall (Vints, Van Craenenbroeck, & Dendale, 2023; Yang, Dou, & Zhang, 2019).
Enhancing Synaptic Plasticity: Exercise-induced BDNF and IGF-1 strengthen existing neural connections, supporting sharper thinking, adaptability, and overall cognitive performance (Severinsen, Pedersen, & Fischer, 2020; Rentería, Gómez, & Torres, 2022).
Reducing Neuroinflammation: Regular strength training helps suppress chronic inflammation and oxidative stress, factors linked to cognitive decline, through myokine signaling (Gao, Li, Chen, & Wang, 2024; Villamil-Parra, Hernández, & Silva, 2024).
Improving Blood Flow and Oxygen Delivery: Strong muscles enhance vascular health, ensuring optimal delivery of nutrients and oxygen to the brain, which supports cognitive function and overall brain resilience (Landers, Landers, & Young, 2025).
Balancing Neurochemistry: Physical exercise modulates key neurotransmitters such as dopamine and serotonin, promoting improved focus, motivation, and emotional balance (Vints, Van Craenenbroeck, & Dendale, 2023).
TIPS to Train for Maximum Brain Benefit
Focus on compound, full-body movements:
Squats, deadlifts, presses, and pulls involve large muscle groups, maximizing myokine release.
Intensity and progression:
Aim for moderate to high intensity — enough to challenge your muscles while maintaining good form.
Frequency:
2–3 sessions per week are sufficient for most people to see both physical and cognitive benefits.
Include aerobic activity:
Combine resistance training with some form of cardio — the synergy boosts BDNF even more.
Cognitive load matters:
Movements that challenge balance, coordination, or learning new skills (e.g., kettlebells, dance, martial arts) further stimulate brain circuitry.
Your muscles aren’t just movers – they’re chemical messengers that keep your brain sharp, resilient, and young. Memory, learning, and focus depend on signals your body can only generate through physical effort. In short: “Train your body, build your brain.”
References
Gao, X., Li, Y., Chen, Z., & Wang, H. (2024). Unlocking the potential of exercise: Harnessing myokines to delay musculoskeletal aging and improve cognitive health. Frontiers in Physiology, 15, 1488375. https://doi.org/10.3389/fphys.2024.1488375
Landers, J. B., Landers, K. R., & Young, N. G. (2025). The effects of blood flow restriction exercise on muscle–brain crosstalk: A systematic review. Muscles, 4(2), 19. https://www.mdpi.com/2813-0413/4/2/19
Rentería, I., Gómez, F., & Torres, M. (2022). The molecular effects of BDNF synthesis on skeletal muscle. Frontiers in Physiology, 13, 934714. https://doi.org/10.3389/fphys.2022.934714
Severinsen, M. C. K., Pedersen, B. K., & Fischer, C. P. (2020). Muscle–organ crosstalk: The emerging roles of myokines. Endocrine Reviews, 41(4), 594–629. https://doi.org/10.1210/endrev/bnaa016
Villamil-Parra, W., Hernández, C., & Silva, M. (2024). Effects of physical exercise on irisin and BDNF levels: Implications for metabolic and mental health. Neuroscience Letters, 803, 136–140. https://doi.org/10.1016/j.neulet.2024.136140
Vints, W. A. J., Van Craenenbroeck, A., & Dendale, P. (2023). Myokines as mediators of exercise-induced cognitive enhancement. Frontiers in Physiology, 14, 10374322. https://doi.org/10.3389/fphys.2023.10374322
Yang, X., Dou, J., & Zhang, L. (2019). Muscle-generated BDNF is a sexually dimorphic myokine. Science Signaling, 12(586), eaau1468. https://doi.org/10.1126/scisignal.aau1468