How our brains may influence our physical endurance

March 31st, 2026

Written by Emma Noel

Your heart is racing, sweat is dripping in your eyes, your brain and muscles are begging you to stop. You look at your watch with the jarring realization that what felt like a five mile run was in fact five minutes of exercise. While the first run often feels like this, over time, you’ll likely realize that enduring longer and harder exercise sessions becomes easier. We intuitively know that consistently going for a run will make us better runners, but until recently the neural pathways underlying why exercise feels better the more that we do it were poorly understood. 

Our ability to sustain long periods of exercise is typically referred to as endurance which is abstractly defined as “the ability to withstand hardship or adversity, especially the ability to sustain a prolonged stressful effort or activity.”¹ Hidden within this definition is the idea that building physical endurance requires both the body and brain. Inside our bodies, physical endurance is improved by activities that strengthen our muscles, lower our heart rate and increase our lung capacity. Mentally, building physical endurance engages our brains through conscious mechanisms, such as maintaining motivation or positive feedback from achieving the desired physique. Historically, it has been thought that the process of building physical endurance (improving cardiovascular fitness, the heart and lungs working together to efficiently use and supply oxygen) worked independently from the brain. 

New research^2,3 is challenging that idea, suggesting that building physical endurance depends not only on the body and brain but on subconscious conversations between them. Importantly, this process appears to be separate from conscious ways that our brains contribute to building endurance, including willpower or effort, and occur outside of our own awareness (in the background). Beyond building endurance, this brain/body connection may even be necessary to maintain the physical benefits of exercise. 

How the brain may mediate physical changes associated with endurance 

In response to exercise, our bodies respond to increases in energy demand by burning energy stores our bodies have built from our food or fuel intake.⁴ When we exercise, we increase our body’s energy demand and trigger these metabolic processes. This is one reason why we see physical impacts of exercise on our bodies, including reduction in body fat and increase in muscle mass. Until now, the idea that our brains could influence, or even hinder, some physical benefits of exercise seemed unlikely, given that this process primarily occurs in our muscles and fat stores. Nonetheless, it is possible that our brains can influence  metabolic responses to exercise. 

Researchers at the University of Pennsylvania set out to understand how the brain may be involved in the relationship between repeated exercise and endurance to get a better idea of if our brains can help control the effects of exercise on our bodies⁵. To do so, they studied mice who underwent repeated exercise and focused on a brain region that is primarily involved in sending the signal to our brains that we are full⁶ called the ventromedial hypothalamus (VMH). Within the VMH, they focused on a group of neurons that had been linked to metabolic processes, called SF1 neurons. Previous research in mice showed that removing SF1 neurons in the VMH reduced the effect of exercise on metabolic changes, suggesting that without SF1 neurons our bodies are less effective at promoting metabolic changes, like reducing body fat, after exercise. This made the researchers wonder whether the same neurons might impact the relationship between repeated exercise and endurance.⁶ 

These previous studies had shown that SF1 neurons are involved in short-term metabolic responses to exercise, but the University of Pennsylvania researchers wanted to know if SF1 neurons may also help mediate longer-term processes like how our bodies respond to repeated exercise.⁵ This is important as it may help shape the way we think about how our bodies adapt to exercise, potentially helping researchers discover ways to promote the long-term benefits of exercise in individuals who are not able to regularly exercise. 

To examine this relationship, the researchers first established that SF1 neurons are activated by bouts of exercise. Once they had established this relationship, they next asked whether they may play a role in long-lasting effects of exercise like building endurance by “turning off” (stopping the action of) SF1 neurons as mice exercised. The researchers reasoned that if turning off the neurons prevented the mice from building endurance then they must play an important role in that process. Indeed, given the same amount of previous running training, animals with their SF1 neurons turned off ran shorter distances on a treadmill prior to exhaustion (a measure of endurance) than animals with functional SF1 neurons. Together, these experiments show that SF1 neurons are not only activated by exercise, but that they may be necessary for building endurance following repeated exercise.

Knowing that SF1 neurons likely influence how mice build endurance, the researchers next asked how these neurons change as the mouse exercises more. To do so, they measured what signals are sent to SF1 neurons from surrounding neurons, called the inputs, using a technique called patch clamping. Patch clamping allows researchers to determine how active a neuron is before and after responding to a stimulus like exercise. They found that the inputs to SF1 neurons were stronger after repeated exercise, making the SF1 neurons themselves quicker to activate. Altogether, this suggests that exercise may be strengthening the pathways that communicate with SF1 neurons and changing how easily they activate to drive metabolic processes. 

Despite these interesting findings, there are still many unknowns, especially about how other processes related to exercise and endurance interact with those studied here. The mechanisms described by this paper examine subconscious processes that relate repeated exercise to changes in endurance, but conscious processes like motivation also play an important role that may work by different neural mechanisms. It is also unknown if and how the neurons that may regulate how our bodies respond physiologically to exercise may relate to the mental and emotional benefits of exercise, including improved mood and reduced stress. 

Despite our general knowledge of exercise and its benefits and government initiatives to promote exercise, only around a quarter of Americans meet the recommended standard for daily exercise (30-60 minutes of moderate exercise).⁸ Given the demands of everyday life, including long work hours, the rising cost of childcare in America, and expenses related to starting exercise (like gym memberships or equipment costs), finding the time and energy to exercise can be difficult. Some individuals also struggle with physical disabilities that limit mobility. Future work building on the research described here may help to design systems that artificially activate neurons that facilitate the positive benefits of exercise, giving the benefits of endurance to individuals who cannot regularly exercise. 

References

1. Definition of ENDURANCE. (n.d.). Www.merriam-Webster.com. https://www.merriam-webster.com/dictionary/endurance
2. Research, I. of M. (US) C. on M. N., & Marriott, B. M. (1994). The Metabolic Responses to Stress and Physical Activity. In http://www.ncbi.nlm.nih.gov. National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK209038/
3. Zhang, J., Chen, D., Sweeney, P., & Yang, Y. (2020). An excitatory ventromedial hypothalamus to paraventricular thalamus circuit that suppresses food intake. Nature Communications, 11(1), 6326. https://doi.org/10.1038/s41467-020-20093-4 ‌
4. Research, I. of M. (US) C. on M. N., & Marriott, B. M. (1994). The Metabolic Responses to Stress and Physical Activity. In http://www.ncbi.nlm.nih.gov. National Academies Press (US). https://www.ncbi.nlm.nih.gov/books/NBK209038/ ‌
5. Kindel, M., Post, R. J., Grose, K., Lantier, L., Hwang, E., Carty, J. R. E., Dohnalová, L., Lepeak, L., Kern, H. C., Villari, R., Goldstein, N., Lo, E., Yeung, A., Richie, L., Skelly, B., Golub, J., Rai, M., Fujikawa, T., Ayala, J. E., & Elmquist, J. K. (2026). Exercise-induced activation of ventromedial hypothalamic steroidogenic factor-1 neurons mediates improvements in endurance. Neuron. https://doi.org/10.1016/j.neuron.2025.12.033 ‌
6. Fujikawa, T., Castorena, C. M., Pearson, M., Kusminski, C. M., Ahmed, N., Battiprolu, P. K., Kim, K. W., Lee, S., Hill, J. A., Scherer, P. E., Holland, W. L., & Elmquist, J. K. (2016). SF-1 expression in the hypothalamus is required for beneficial metabolic effects of exercise. ELife, 5. https://doi.org/10.7554/elife.18206 ‌
7. Talya Minsberg. (2025, January 21). Are Americans Doing Fitness Wrong? The New York Times. 

Cover photo by Andrew Rashotte from Burst