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. 2003 Apr;17(6):690-2.
doi: 10.1096/fj.02-0533fje. Epub 2003 Feb 5.

Genotype and age influence the effect of caloric intake on mortality in mice

Michael J Forster  1 , Paul Morris, Rajindar S Sohal
Affiliations

Genotype and age influence the effect of caloric intake on mortality in mice

Michael J Forster et al. FASEB J. 2003 Apr.

Abstract

Long-term caloric restriction (CR) has been repeatedly shown to increase life span and delay the onset of age-associated pathologies in laboratory mice and rats. The purpose of the current study was to determine whether the CR-associated increase in life span occurs in all strains of mice or only in some genotypes and whether the effects of CR and ad libitum (AL) feeding on mortality accrue gradually or are rapidly inducible and reversible. In one experiment, groups of male C57BL/6, DBA/2, and B6D2F1 mice were fed AL or CR (60% of AL) diets beginning at 4 months of age until death. In the companion study, separate groups of mice were maintained chronically on AL or CR regimens until 7, 17, or 22-24 months of age, after which, half of each AL and CR group was switched to the opposite regimen for 11 wk. This procedure yielded four experimental groups for each genotype, namely AL-->AL, AL-->CR, CR-->CR, and CR-->AL, designated according to long-term and short-term caloric regimen, respectively. Long-term CR resulted in increased median and maximum life span in C57BL/6 and B6D2F1 mice but failed to affect either parameter in the DBA/2 mice. The shift from AL-->CR increased mortality in 17- and 24-month-old mice, whereas the shift from CR-->AL did not significantly affect mortality of any age group. Such increased risk of mortality following implementation of CR at older ages was evident in all three strains but was most dramatic in DBA/2 mice. Results of this study indicate that CR does not have beneficial effects in all strains of mice, and it increases rather than decreases mortality if initiated in advanced age.

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Figures

Figure 1
Figure 1. Survivorship of C57BL/6, B6D2F1, and DBA/2 mice as a function of age
Separate groups of each genotype were maintained from 4 months of age under ad libitum (AL) or 40% calorie-restricted (CR) feeding regimens as described in Materials and Methods.
Figure 2
Figure 2. Mean body weight (grams; ±SE) of surviving C57BL/6, B6D2F1, and DBA/2 mice as a function of age
Separate groups of each genotype were maintained from 4 months of age under ad libitum (AL) or 40% calorie-restricted (CR) feeding regimens as described in Materials and Methods. Data not shown for cells with less than four mice surviving.
Figure 3
Figure 3. Probability of survival over a period of 11 wk following shifts in caloric intake for separate age groups (left to right panels) of C57BL/6, B6D2F1, and DBA/2 mice
Separate groups of each genotype were maintained chronically under AL or CR before the shifts.
Figure 4
Figure 4. Mean body weight (grams; ±SE) following two-way shifts in caloric intake for different age groups (left to right panels) of C57BL/6, B6D2F1, and DBA/2 mice
Separate groups of each genotype were maintained chronically under AL or CR before the shifts.
See this image and copyright information in PMC

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