1. Division of Molecular Genetics, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187, Japan
2. The 2nd Department of Internal Medicine, University of Gunma School of Medicine, 3-39-22, Showa, Maebashi, Gunma 371, Japan
3. Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113, Japan
4. Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumakoto 862, Japan
5. Lead Optimization Research Laboratory, Tanabe Seiyaku Co. Ltd, 2-2-50 Kawagishi, Toda, Saitama 335, Japan
6. Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, 3-6-6 Asahimachi, Machidashi, Tokyo 194, Japan
7. Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, 118 Shimotagari, Nagaizumi, Sunto, Shizuoka 411, Japan
8. Core Research for Evolutional Science & Technology (CREST), JRDC and
9. Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565, Japan

Correspondence to: Makoto Kuro-o¹Yo-ichi Nabeshima^1,8,9 Correspondence and requests for materials should be addressed to M.K. (e-mail: Email: kuroo@ncnaxp.ncnp.go.jp) or Y.N.(e-mail: Email: nabemr@imcb.osaka-u.ac.jp).The nucleotide sequence data will appear in the DDBJ, EMBL and GenBank nucleotide sequence databases under the accession numbers AB005141 and AB005142 for mouse and human mRNA for klotho, respectively.

Abstract

A new gene, termed klotho, has been identified that is involved in the suppression of several ageing phenotypes. A defect in klotho gene expression in the mouse results in a syndrome that resembles human ageing, including a short lifespan, infertility, arteriosclerosis, skin atrophy, osteoporosis and emphysema. The gene encodes a membrane protein that shares sequence similarity with the -glucosidase enzymes. The klotho gene product may function as part of a signalling pathway that regulates ageing in vivo and morbidity in age-related diseases.