Cognition impairment in the genetic model of aging klotho gene mutant mice: a role of oxidative stress.

Taku Nagai, Kiyofumi Yamada, Hyoung Chun Kim, Yong Sun Kim, Yukihiro Noda, Akihiro Imura, Yo ichi Nabeshima, Toshitaka Nabeshima

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196 Citations (Scopus)

Abstract

A new gene, termed klotho, is associated with the suppression of several aging phenotypes. Because high expression of klotho gene was detected in the brain, it would be plausible that klotho gene is involved in the regulation of brain aging. We investigated the changes in mnemonic function accompanying aging in klotho mutant mice. Cognitive function measured by novel-object recognition and conditioned-fear tests in klotho mutant mice was normal at the age of 6 wk, but markedly impaired at the age of 7 wk. Lipid (malondialdehyde) and DNA (8-hydroxy-2'-deoxyguanosine) peroxide levels in the hippocampus of klotho mutant mice increased at the age of 5 wk, 2 wk before the development of cognition deficits. Pro-death Bax increased, whereas anti-death Bcl-2 and Bcl-XL decreased, and apoptotic TUNEL-positive cells were detected in the hippocampus of klotho mutant mice at the age of 7 wk. A potent antioxidant, a-tocopherol, prevented cognition impairment and lipid peroxide accumulation and decreased the number of apoptotic cells in klotho mutant mice. These results suggest that oxidative stress has a crucial role in the aging-associated cognition impairment in klotho mutant mice. Klotho protein may be involved in the regulation of antioxidative defense.

Original languageEnglish
Pages (from-to)50-52
Number of pages3
JournalThe FASEB journal : official publication of the Federation of American Societies for Experimental Biology
Volume17
Issue number1
Publication statusPublished - 01-2003
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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