While radiation nephropathy is a major problem associated with radiotherapy, the 
exact mechanisms underlying its pathogenesis and the mediators involved in 
kidney deterioration remain to be elucidated. In view of the finding that 
senescence is typically increased post‑irradiation, the present study examined 
whether ionizing radiation may cause kidney injury by enhancing premature 
senescence. The present study explored the relevance of the aging suppressor, 
Klotho, which has anti‑aging activity and is highly expressed in murine renal 
cells/kidney tissues, under irradiation conditions. Firstly, the effects of 
radiation on mouse inner medullary collecting duct‑3 (mIMCD‑3) cells and kidney 
tissues of mice were assessed. Subsequently, the mRNA expression levels of 
Klotho, TNF‑α and ADAM metallopeptidase domain (ADAM)9/10/17 were analyzed by 
reverse transcription‑quantitative PCR following exposure to radiation. In 
addition, the levels of these proteins were measured by western blotting or 
ELISA. The results revealed that irradiation of mIMCD‑3 cells clearly triggered 
cellular senescence. Notably, Klotho gene expression was considerably decreased 
in radiation‑exposed mIMCD‑3 cells and in the kidney tissues of irradiated 
BALB/c mice, and the corresponding translated protein was consistently expressed 
following radiation exposure. Moreover, expression of TNF‑α, a negative 
regulator of Klotho, was significantly increased, whereas ADAM9/10/17, an 
ectodomain shedding enzyme of Klotho, was decreased in irradiated mIMCD‑3 cells 
and in the kidney tissues of BALB/c mice. Collectively, these data suggested 
that TNF‑α‑mediated inhibition of Klotho expression and blockage of soluble 
Klotho formation via decreased ADAM expression following irradiation may 
contribute to the development of renal dysfunction through acceleration of 
radiation‑induced cellular senescence.