Aerobic exercise induces many adaptive changes in the whole body and improves 
metabolic characteristics. Klotho, an anti-aging gene, is mainly expressed in 
the brain and kidney. The roles of Klotho in the brain and kidney during aerobic 
exercise remain largely unknown. The present study aimed to determine whether 
aerobic exercise could influence the expression of Klotho, decrease reactive 
oxygen species (ROS) and prolong life span. Sprague Dawley rats were exercised 
on a motor treadmill. Klotho mRNA and protein expression levels in rat brain and 
kidney tissues were examined using reverse transcription-quantitative polymerase 
chain reaction and western blotting, respectively. ROS production was detected 
following intermittent aerobic exercise (IAE) or continuous aerobic exercise 
(CAE). Kaplan-Meier curve analysis demonstrated that aerobic exercise 
significantly improved rat survival (P<0.001). The ROS levels in rat brain and 
kidney tissues were decreased in the aerobic exercise groups compared with the 
control group (P<0.05). In addition, Klotho mRNA and protein expression levels 
were increased significantly following aerobic exercise compared with controls 
(P<0.05). There was no significant difference between the IAE and CAE groups in 
any experiments (P>0.05). These results suggest that aerobic exercise-stimulated 
Klotho upregulation extends the life span by attenuating the excess production 
of ROS in the brain and kidney. As Klotho exhibits a potential anti-aging 
effect, promoting Klotho expression through aerobic exercise may be a novel 
approach for the prevention and treatment of aging and aging-related diseases.