Genotype and age influence the effect of caloric intake on mortality in mice
Genotype and age influence the effect of caloric intake on mortality in mice
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DOI：
10.1096/fj.02-0533fje
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发表时间：
2003-02-01
期刊：
影响因子：
4.8
通讯作者：
Sohal, RS
中科院分区：
文献类型：
--
作者：
Forster, MJ;Morris, P;Sohal, RS
在实验室小鼠和大鼠中，长期热量限制(CR)被反复证明可以延长寿命并延缓与年龄相关的疾病的发生。本研究的目的是确定CR相关的寿命延长是否发生在所有品系的小鼠中，还是仅发生在某些基因类型中，以及CR和随意喂养(AL)对死亡率的影响是逐渐增加的，还是快速诱导和可逆的。在一项实验中，雄性C57BL/6、DBA/2和B6D2F(1)组小鼠从4个月龄开始饲喂AL或CR(60%的AL)，直到死亡。在配对研究中，不同的组小鼠长期服用AL或CR方案，直到7、17或22-24个月龄，之后，每组AL和CR组的一半切换到相反的方案11wk。这一程序为每种基因型产生了四个试验组，即AL-->；AL、AL-->；CR、CR-->；CR和CR-->；AL，分别按长期和短期热量方案指定。长期CR可延长C57BL/6和B6D2F(1)小鼠的中位寿命和最长寿命，但对DBA/2小鼠的中位寿命和最长寿命均无影响。从AL-->；AL的转变增加了17和24个月龄小鼠的死亡率，而从CR->；AL的转变对任何年龄组的死亡率都没有显著影响。在老年实施CR后，死亡风险的增加在所有三个品系中都是明显的，但在DBA/2小鼠中表现最显著。这项研究的结果表明，CR并不是对所有品系的小鼠都有好处，如果在高龄时开始使用，它会增加而不是降低死亡率。
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 B6D2F(1) 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 B6D2F(1) 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.