eli5: What actually makes you tired from doing something strenuous?

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Like when you run and you “run out of gas”, what happens inside the body that makes you stop?

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In your muscles, you have chemicals called ATP (adenosine tri-phosphate). These molecules are what allows the muscle cells to contract, which is what causes your muscles to do what they do. When you run out, it takes time before your muscle cells “refuel”. A chemical called creatine helps re-charge the ATP so it can be used again. This chemical is stored in your muscles in some amounts, but it’s easy to run out. This is what allows the most “explosive” kind of movement.

When you’re out of these (typically after 10-ish seconds), your muscle cells need to find an alternative source of energy. They can resort to anaerobic (meaning without sufficient access to oxygen) “refueling”, with carbohydrates as fuel, but this generates an unpleasant waste product called lactic acid. This waste product is what causes what many describe as a burning sensation in your muscles.

If too much of this chemical builds up, it will be more and more difficult to keep moving without giving your body time to get rid of the waste products. Getting rid of them takes more time than it took to create them, so you need to rest.

If the exercise is light enough, your body will be able to regenerate energy fast enough aerobically, meaning no lactic acid builds up, and your muscles don’t get tired. This is why we can practically walk for miles without having to stop because of exhaustion. There’s no build-up of waste products, so there’s no need to stop to let them get “flushed out”.