Neurobiology of Aging
Volume 28, Issue 10 , Pages 1613-1622, October 2007

Caloric restriction suppresses apoptotic cell death in the mammalian cochlea and leads to prevention of presbycusis

  • Shinichi Someya

      Affiliations

    • Departments of Genetics & Medical Genetics, University of Wisconsin, Madison, WI 53706, USA
    • Department of Applied Biological Chemistry, University of Tokyo, Tokyo 113-8657, Japan
    • ,
  • Tatsuya Yamasoba

      Affiliations

    • Department of Otolaryngology, University of Tokyo, Tokyo 113-8655, Japan
    • ,
  • Richard Weindruch

      Affiliations

    • Department of Medicine and Veterans Administration Hospital, University of Wisconsin, Madison, WI 53705, USA
    • ,
  • Tomas A. Prolla

      Affiliations

    • Departments of Genetics & Medical Genetics, University of Wisconsin, Madison, WI 53706, USA
    • ,
  • Masaru Tanokura

      Affiliations

    • Department of Applied Biological Chemistry, University of Tokyo, Tokyo 113-8657, Japan
    • Corresponding Author InformationCorresponding author. Tel.: +81 3 5841 5165; fax: +81 3 5841 8023.

Received 22 March 2006; received in revised form 20 June 2006; accepted 22 June 2006. published online 10 August 2006.

Abstract 

Presbycusis is characterized by an age-related progressive decline of auditory function, and arises mainly from the degeneration of hair cells or spiral ganglion (SG) cells in the cochlea. Here we show that caloric restriction suppresses apoptotic cell death in the mouse cochlea and prevents late onset of presbycusis. Calorie restricted (CR) mice, which maintained body weight at the same level as that of young control (YC) mice, retained normal hearing and showed no cochlear degeneration. CR mice also showed a significant reduction in the number of TUNEL-positive cells and cleaved caspase-3-positive cells relative to middle-age control (MC) mice. Microarray analysis revealed that CR down-regulated the expression of 24 apoptotic genes, including Bak and Bim. Taken together, our findings suggest that loss of critical cells through apoptosis is an important mechanism of presbycusis in mammals, and that CR can retard this process by suppressing apoptosis in the inner ear tissue.

Keywords: Presbycusis, Hearing loss, Calorie restriction, Apoptosis, Aging

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PII: S0197-4580(06)00233-8

doi:10.1016/j.neurobiolaging.2006.06.024

Neurobiology of Aging
Volume 28, Issue 10 , Pages 1613-1622, October 2007

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