2006 Volume 43 Issue 3 Pages 342-344
The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g. arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, skin atrophy). We have demonstrated that mice deficient for the klotho gene show endothelial dysfunction as manifested by an attenuated response of aortic relaxation in response to acetylcholine stimulation. Systemic nitric oxide production was also significantly reduced in klotho deficient mice. Oxidative stress was increased in klotho deficient mice. The klotho gene delivery improves multiple aging phenotypes. Our findings establish the basis for the therapeutic potential of klotho gene delivery in age-related diseases.