The Durk Pearson & Sandy Shaw®
Life Extension NewsTM
Volume 6 No.
3 • June 2003
Caloric Restriction Does Not Increase the Lifespan of All Breeds of Mice
The authors of a recent paper carried out a study to determine whether caloric restriction (CR) can increase the lifespan in all genetic strains of mice and whether the beneficial effects of CR accrue gradually or whether they are rapidly induced and reversible when there is a shift from ad libitum (AL) feeding to CR.
They compared the effects of CR on two mouse strains, C57BL/6 and DBA/2, and their first-generation hybrids, B6D2F1. Under AL conditions, the median lifespans of the strains of mice differed only slightly, with B6D2F1 and C57BL/6 mice living 1 to 2 months longer than DBA/2. However, under CR conditions, the C57BL/6 and B6D2F1 had a 6-to-7-month-longer median lifespan and an 8-to-11-month-longer maximum lifespan, whereas in the DBA/2 mice, CR resulted in a slight decrease in lifespan. Hence, CR did not increase the lifespan of all the strains studied.
In the second part of the study, one-half of the original group of AL mice in each genotype and age were switched and maintained in CR. Half of the original CR mice were switched to AL and maintained at AL. The groups were kept on these switched regimens for at least 11 weeks, along with control groups that remained on their original AL or CR regimens. The results showed that switching CR mice to AL at advanced age had little or no effect on mortality over the 11-week period compared to CR mice maintained on CR. The authors suggest that the beneficial effects of CR are, therefore, not rapidly reversible. Switching old AL-fed mice to CR failed to increase lifespan; in fact, it tended to increase mortality compared to AL mice maintained on AL. The increased mortality was evident by 17 months in the DBA/2 and C57BL/6 mice, but not until 24 months in the B6D2F1. The authors conclude that “CR instituted at a relatively advanced age may be without benefit and, depending on genotype, could have significant deleterious effects.”
The genetic difference between strains of mice is far, far smaller than the genetic difference between humans and mice or even humans and monkeys. Hence, since CR does not increase the lifespan of all mouse strains, and even if CR ultimately proves to increase mean or maximum lifespan in monkeys, it is still not clear whether lifelong caloric restriction would increase mean or maximum lifespan in humans.
This is an ideal problem for study with gene-expression microarray chips. The expression of many genes is altered by CR. The expression of the critical genes for the life-extending effect of CR will be different in the DBA/2 mice as compared to the C57BL6 and B6D2F mice. Once the genes that are responsible for the differences in CR in the mouse strains are identified, the effect of CR can then be studied on the homologous genes in human cells. We will be helping to support this research.
- Forster, Morris, Sohal. Genotype and age influence the effect of caloric intake on mortality in mice. FASEB J, Feb 5, 2003.