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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 β-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.

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Acknowledgements

We thank E. Ozawa, T. Ishikawa, K. Hanaoka and I. Nonaka for earlier contributions to this work, T. Matsuzaki, S. Kameya and Y. Hiroi for maintaining mice, and H. Yamato and Y. Nagai for bone analyses.

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Affiliations

  1. *Division of Molecular Genetics, National Institute of Neuroscience, NCNP, 4-1-1 Ogawahigashi, Kodaira, Tokyo 187, Japan

    • Makoto Kuro-o
    • , Yutaka Matsumura
    • , Hiroki Aizawa
    • , Takako Shiraki-Iida
    •  & Yo-ichi Nabeshima
  2. †The 2nd Department of Internal Medicine, University of Gunma School of Medicine, 3-39-22, Showa, Maebashi, Gunma 371, Japan

    • Yutaka Matsumura
    • , Hiroki Aizawa
    • , Tatsuo Suga
    • , Toshihiro Utsugi
    • , Yoshio Ohyama
    • , Masahiko Kurabayashi
    •  & Ryozo Nagai
  3. ‡Department of Orthopaedic Surgery, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113, Japan

    • Hiroshi Kawaguchi
  4. §Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumakoto 862, Japan

    • Tadashi Kaname
  5. Lead Optimization Research Laboratory, Tanabe Seiyaku Co. Ltd, 2-2-50 Kawagishi, Toda, Saitama 335, Japan

    • Eisuke Kume
    •  & Hitoshi Iwasaki
  6. ¶Tokyo Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, 3-6-6 Asahimachi, Machidashi, Tokyo 194, Japan

    • Akihiro Iida
    •  & Takako Shiraki-Iida
  7. #Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co. Ltd, 118 Shimotagari, Nagaizumi, Sunto, Shizuoka 411, Japan

    • Satoshi Nishikawa
  8. Core Research for Evolutional Science & Technology (CREST), JRDC and

    • Ryozo Nagai
    •  & Yo-ichi Nabeshima
  9. ††Institute for Molecular and Cellular Biology, Osaka University, 1-3 Yamada-oka, Suita, Osaka 565, Japan

    • Yo-ichi Nabeshima

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Correspondence to Makoto Kuro-o or Yo-ichi Nabeshima.

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DOI

https://doi.org/10.1038/36285

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