Researchers here establish that calorie restriction started in late life does not extend life in mice, contradicting older research results showing that it does to some degree. This may be a difference resulting from mouse lineage or housing or diet prior to applying calorie restriction. The researchers here point to the behavior of fat tissue in the older mice as being important, so we might think that perhaps the mice in the two studies began calorie restriction with differing amounts of fat tissue.
In any case this is a reminder that the practice of calorie restriction - and therefore treatments that mimic some of its effects - are a method of slowing aging, not reversing aging. For the full benefit to emerge, calories must be restricted, or the treatment applied, throughout much of life. This makes it a comparatively poor area of study when it comes to the development of human therapies to treat aging.
Mice live longer and are healthier in old age if they are given 40 percent less to eat after reaching adulthood than animals who are allowed to eat as much as they want. The dieting mice are fed with food enriched with vitamins and minerals to prevent malnutrition. But if food intake is first reduced in mice first start eating less food when they are already seniors, the researchers observe little or no effect on the life expectancy of the mice. On the other hand, when mice are allowed to eat as much as they like after a period of reduced food intake, they have no long-term protection, so reduced food intake has to be sustained for mice to reap the benefits. Reduced food intake must therefore be implemented early and be sustained until the end of their lives to have positive effects on health in old age.
But why do older mice no longer react to the change in diet? Researchers investigated gene activity in different organs. While the gene activity in the liver quickly adapted when mice are transferred to a restricted diet, the scientists observed a 'memory effect' in the fat tissue of older animals. Although the mice lose weight, the activity of the genes in the fat tissue is similar to that of the mice that continue to eat as much as they want. In addition, the fat composition in old mice does not change as much as in young mice.
This memory effect mainly affects mitochondria, the cells' power houses, which play an important role in the ageing process. Usually, reduced food intake leads to increased formation of mitochondria in fatty tissue. But the study showed that this is no longer the case when older mice are switched to a lower calorie diet. This inability to change at the genetic and metabolic levels may contribute to the shortened lifespan of these animals.