α-Klotho, a multifunctional protein, has been demonstrated to protect tissues 
from injury via anti-oxidation and anti-inflammatory effects. The expression of 
α-klotho is regulated by several physiological and pathological factors, 
including acute inflammatory stress, oxidative stress, hypertension, and chronic 
renal failure. Exhaustive exercise has been reported to result in tissue damage, 
which is induced by inflammation, oxidative stress, and energy metabolism 
disturbance. However, little is known about the effects of exhaustive exercise 
on the expression of α-klotho in various tissues. To determine the effects, the 
treadmill exhaustion test in mice was performed and the mice were sacrificed at 
different time points following exhaustive exercise. Our results confirmed that 
the full-length (130 kDa) and shorter-form (65 kDa) α-klotho were primarily 
expressed in the kidneys. Moreover, we found that, except for the kidneys and 
brain, other tissues primarily expressed the shorter-form α-klotho, including 
liver, which was in contrast to previous reports. Furthermore, the shorter-form 
α-klotho was decreased immediately following the acute exhaustive exercise and 
was then restored to the pre-exercise level or even higher levels in the next 
few days. Our results indicate that α-klotho may play a key role in the body 
exhaustion and recovery following exhaustive exercise.