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Creative Minds: The Muscle-Brain Connection

Posted on by Dr. Francis Collins

Muscle activity and brain function

There’s mounting evidence that exercise has a powerful effect on the human brain. For example, many studies have shown that physical activity appears to reduce the incidence of depression. Exercise can also delay or possibly even prevent Alzheimer’s disease, as well as easing symptoms in people who have these disorders [1, 2, 3, 4, 5]. But how, exactly, does getting our legs moving and our hearts pumping exert a positive influence on our brains?

Two scientists at Stanford University School of Medicine are out to get some answers to this important question. They have proposed that when we exercise, our muscles secrete a factor or combination of factors into the bloodstream, leading to structural and functional changes in the brain.

Winners of a 2013 NIH Director’s Transformative Research Award, Tony Wyss-Coray and Thomas Rando plan to collect all of the molecules that muscles secrete that enable them to communicate with other cells. These molecules include hormones, growth factors, and small proteins called cytokines that are important in cell signaling. The Stanford duo suspects that the key to exercise’s beneficial impact on the brain may lie in its effect on this collection of molecules—which they have dubbed “the communicome.”

To study the communicome, Wyss-Coray and Rando will use a technique called parabiosis to couple the circulatory systems of physically active mice with mice that are less active. If the “couch potato” mice benefit from the blood of the active mice, then the team will analyze the blood to find the responsible factor(s).

This is definitely high-risk high-reward research. It won’t be easy, but finding molecules that mimic exercise’s brain-boosting effects may open the door to new ways of preventing or treating age-related cognitive declines and a wide range of other neurological conditions. This is especially important for people for whom it is difficult or even hazardous to exercise because of conditions such as arthritis, osteoporosis, and Alzheimer’s disease and other forms of dementia.

Still, for the vast majority of us, there’s no reason to sit around waiting for results of the latest research on the exercise-brain connection. Put on your sneakers, hop on your bike, grab your gym bag, or do whatever else it takes to get yourself moving on a regular basis. It will do your entire body good—and that’s a fact.

Head shots of Wyss-Coray and Rando
Credit: Stanford School of Medicine; The NIH Record


[1] Physical activity and risk of neurodegenerative disease: a systematic review of prospective evidence. Hamer M, Chida Y. Psychol Med. 2009 Jan;39(1):3-11.

[2] Cardiovascular fitness in males at age 18 and risk of serious depression in adulthood: Swedish prospective population-based study. Åberg MA, Waern M, Nyberg J, Pedersen NL, Bergh Y, Åberg ND, Nilsson M, Kuhn HG, Torén K. Br J Psychiatry. 2012 Nov;201(5):352-9.

[3] Physical activity and risk of cognitive decline: a meta-analysis of prospective studies. Sofi F, Valecchi D, Bacci D, Abbate R, Gensini GF, Casini A, Macchi C. J Intern Med. 2011 Jan;269(1):107-17.

[4] Physical activity reduces hippocampal atrophy in elders at genetic risk for Alzheimer’s disease. Smith JC, Nielson KA, Woodard JL, Seidenberg M, Durgerian S, Hazlett KE, Figueroa CM, Kandah CC, Kay CD, Matthews MA, Rao SM. Front Aging Neurosci. 2014 Apr 23;6:61.

[5] Physical exercise as a preventive or disease-modifying treatment of dementia and brain aging. Ahlskog JE, Geda YE, Graff-Radford NR, Petersen RC. Mayo Clin Proc. 2011 Sep;86(9):876-84.


The Common Fund (NIH)

NIH Director’s Transformative Research Award Program

Tony Wyss-Coray and Thomas A. Rando, A New Muscle-Brain Axis Underlying the Cognitive Benefits of Physical Activity
, Stanford University and VA Palo Alto, CA

Wyss-Coray Lab, Stanford University

Rando Lab, Stanford University

Benefits of Exercise (NIHSeniorHealth)

NIH support: Common Fund; National Institute on Aging; National Institute of Arthritis and Musculoskeletal and Skin Diseases


  • Fernando Aguirre P says:

    EXCELENTE. Brain, exercise and the learning process in adolescents. Is it possible to demonstrate this??

  • Kevin McNulty says:

    This should come as no surprise. It is not a surprise to me. I have always felt better, worked better, and thought better after vigorous exercise.

  • Joseph A. Salmon, Jr. says:

    I just attended the NIH Researchfest. Please inform me fully about this research.

  • C.D.L. says:


  • Colin Pinto says:

    These studies may help unlock, at a physiological level the secret behind Qi-gong. The gentle, rhythmic movements of Qigong reduce stress, build stamina, and enhance the immune system. It has also said to improve cardiovascular, respiratory, circulatory, and digestive functions.

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