• Open Access

Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening

Authors

  • Chen-Yu Liao,

    1. Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
    2. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
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  • Brad A. Rikke,

    1. Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA
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    • *

      These authors contributed equally to this study.

  • Thomas E. Johnson,

    1. Institute for Behavioral Genetics, University of Colorado, Boulder, CO 80309, USA
    2. Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA
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    • *

      These authors contributed equally to this study.

  • Vivian Diaz,

    1. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
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  • James F. Nelson

    1. Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
    2. Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA
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    • *

      These authors contributed equally to this study.


James F. Nelson, Department of Physiology and Barshop Institute for Longevity and Aging Studies, 15355 Lambda Drive, University of Texas Health Science Center at San Antonio, TX 78245, USA. Tel.: +1 210 562 6132;
fax: +1 210 562 6130; e-mail: nelsonj@uthscsa.edu

Summary

Chronic dietary restriction (DR) is considered among the most robust life-extending interventions, but several reports indicate that DR does not always extend and may even shorten lifespan in some genotypes. An unbiased genetic screen of the lifespan response to DR has been lacking. Here, we measured the effect of one commonly used level of DR (40% reduction in food intake) on mean lifespan of virgin males and females in 41 recombinant inbred strains of mice. Mean strain-specific lifespan varied two to threefold under ad libitum (AL) feeding and 6- to 10-fold under DR, in males and females respectively. Notably, DR shortened lifespan in more strains than those in which it lengthened life. Food intake and female fertility varied markedly among strains under AL feeding, but neither predicted DR survival: therefore, strains in which DR shortened lifespan did not have low food intake or poor reproductive potential. Finally, strain-specific lifespans under DR and AL feeding were not correlated, indicating that the genetic determinants of lifespan under these two conditions differ. These results demonstrate that the lifespan response to a single level of DR exhibits wide variation amenable to genetic analysis. They also show that DR can shorten lifespan in inbred mice. Although strains with shortened lifespan under 40% DR may not respond negatively under less stringent DR, the results raise the possibility that life extension by DR may not be universal.

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