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. 2006 Dec;5(6):441-9.
doi: 10.1111/j.1474-9726.2006.00236.x. Epub 2006 Oct 27.

Does caloric restriction extend life in wild mice?

James M Harper  1 , Charles W Leathers, Steven N Austad
Affiliations

Does caloric restriction extend life in wild mice?

James M Harper et al. Aging Cell. 2006 Dec.

Abstract

To investigate whether mice genetically unaltered by many generations of laboratory selection exhibit similar hormonal and demographic responses to caloric restriction (CR) as laboratory rodents, we performed CR on cohorts of genetically heterogeneous male mice which were grandoffspring of wild-caught ancestors. Although hormonal changes, specifically an increase in corticosterone and decrease in testosterone, mimicked those seen in laboratory-adapted rodents, we found no difference in mean longevity between ad libitum (AL) and CR dietary groups, although a maximum likelihood fitted Gompertz mortality model indicated a significantly shallower slope and higher intercept for the CR group. This result was due to higher mortality in CR animals early in life, but lower mortality late in life. A subset of animals may have exhibited the standard demographic response to CR in that the longest-lived 8.1% of our animals were all from the CR group. Despite the lack of a robust mean longevity difference between groups, we did note a strong anticancer effect of CR as seen in laboratory rodents. Three plausible interpretations of our results are the following: (1) animals not selected under laboratory conditions do not show the typical CR effect; (2) because wild-derived animals eat less when fed AL, our restriction regime was too severe to see the CR effect; or (3) there is genetic variation for the CR effect in wild populations; variants that respond to CR with extended life are inadvertently selected for under conditions of laboratory domestication.

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Figures

Fig. 1
Fig. 1
(A) Longitudinal trends in body weights of ad libitum (AL) and caloric restriction (CR) wild-derived mice. (B) Longitudinal trends in CR animals that are long- [> 143 weeks (1000 days)] or short-lived (< 143 weeks).
Fig. 2
Fig. 2
Fecal (A) corticosterone and (B) testosterone concentrations in caloric restriction (CR) vs. ad libitum (AL) mice. ***P ≤ 0.001; **0.001 < P ≤ 0.01; *0.01 < P < 0.05 for differences between CR and AL at equivalent times.
Fig. 3
Fig. 3
Longevity of ad libitum (AL) and caloric restriction (CR) animals. (A) Comparative survival shows no statistical difference. Numbers in parenthesis are mean values for each group. (B) Distribution of deaths in the two groups. CR animals show more early deaths but fewer later deaths than the AL group. (C) Age-specific hazard rates and Gompertz plots for the two groups. Despite the lack of a difference in survival between the groups, there is a statistical difference in Gompertz parameters (P = 0.014).
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