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Does caloric restriction extend life in wild mice?

James M Harper1, Charles W Leathers, Steven N Austad

  • 1Department of Biological Sciences, University of Idaho, Moscow, ID 83844, USA.

Aging Cell
|October 24, 2006
PubMed
Summary

Caloric restriction (CR) in wild-derived mice altered hormones like laboratory rodents but did not extend mean lifespan. However, CR showed a significant anticancer effect and potentially extended maximum lifespan in this genetically diverse population.

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Area of Science:

  • Gerontology
  • Animal Models
  • Nutritional Science

Background:

  • Caloric restriction (CR) is known to extend lifespan and healthspan in laboratory rodents.
  • Laboratory-adapted rodents show specific hormonal and demographic responses to CR.
  • It remains unclear if these CR effects translate to genetically diverse rodent populations not subjected to extensive laboratory selection.

Purpose of the Study:

  • To determine if genetically heterogeneous, wild-derived mice exhibit similar hormonal and demographic responses to CR as laboratory-adapted rodents.
  • To investigate the impact of CR on mean and maximum longevity in a wild-derived mouse model.
  • To assess the anticancer effects of CR in this population.

Main Methods:

  • Genetically heterogeneous male mice, grandoffspring of wild-caught ancestors, were subjected to CR or ad libitum (AL) feeding.

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  • Hormonal levels (corticosterone, testosterone) and mortality patterns were monitored.
  • Gompertz mortality models were used to analyze demographic responses.
  • Anticancer effects were evaluated.

    • Main Results:

    • CR induced hormonal changes (increased corticosterone, decreased testosterone) similar to laboratory rodents.
    • No significant difference in mean longevity was observed between AL and CR groups.
    • CR resulted in higher early-life mortality but lower late-life mortality, with the longest-lived animals all in the CR group.
    • A significant anticancer effect of CR was observed, consistent with findings in laboratory rodents.

    Conclusions:

    • Wild-derived mice show some conserved hormonal responses to CR but not a clear extension of mean lifespan.
    • The lack of extended mean lifespan may be due to the severity of the CR regimen for this population or inherent genetic variation.
    • CR demonstrates a potent anticancer effect in wild-derived mice, suggesting conserved benefits.
    • Laboratory domestication may have inadvertently selected for genetic variants that respond to CR with extended life.