Over the last twenty years researchers have undertaken a great many rodent studies of calorie restriction, also known as dietary restriction, and its ability to improve health, slow aging, and extend longevity. As this paper goes to show there is much left to learn, however. In particular, the relationships between degrees of calorie restriction, enhanced longevity, and benefits to particular narrow aspects of health are complex. One of the unexpected outcomes here is that mild calorie restriction has a very similar outcome in terms of life expectancy as that of more rigorous calorie restriction - at least in one particular commonly used laboratory rat lineage. That qualification is necessary, as results have varied over a selection of various lineages.
Given that short-lived species such as mice and rats have far more plastic life spans than long-lived species such as humans, the long-term characteristics of the calorie restriction response when it comes to aging and disease are likely to be quite different for us in many of the important details. Certainly it doesn't extend human life by up to 40% as it does in mice, as that outcome would have been noticed centuries ago at the very least. This is the case even though many of the short-term measures of changing metabolism in response to calorie restriction are similar for all mammals, and it has been shown to result in notable health benefits for human practitioners.
Dietary restriction (DR) has become the gold standard to which manipulations that increase life span and appear to retard aging are compared. DR has been shown to increase life span and reduce or delay the increase in age-related pathologies and the decline in most physiological functions in numerous genotypes of laboratory rodents. DR increases the life span of a wide variety of other organisms. These data have led to the view that the effect of DR on longevity and aging is universal, a view that was reinforced in 2009 with the first data showing that DR significantly decreased the incidence of age-related deaths and delayed the onset of age-related pathologies in rhesus monkeys. The universality of the effect of DR on longevity was called into question in 2010 when researchers reported the effect of DR on approximately 40 different recombinant inbred lines of male and female mice. Surprisingly, approximately one-third of the mice showed a decrease in life span on the DR diet; one-third showed no effect of DR on life span; and only one-third showed the expected increase in life span.
One possible explanation for the recent contradictory data on DR is that the level of DR required to increase life span is genotype dependent, and because the previous studies used only one, relatively high, level of DR, which might have had a negative effect (instead, lower levels of DR might increase life span). The standard DR diet that is usually used in DR rodent studies one in which rodents are fed 60% of the diet consumed by animals fed ad libitum (AL) (i.e., 40% DR). This is the level of restriction used by the National Institute on Aging (NIA) for their aged rodent colonies, which have been available to investigators studying aging. It is generally believed that the increase in life span is directly related to the level of DR, that is, increasing the level of restriction leads to a greater increase in life span up to a certain point (e.g., around 60% DR) where further restriction is harmful. However, there are only limited data to support this view.
The purpose of this study was to determine whether a modest level of DR (10% DR) could increase the life span of male F344 rats and compare its effects on life span and pathology to the effects of 40% DR. We found that 10% DR significantly increased mean life span, and surprisingly, the increase in mean life span obtained by 10% DR was similar to that observed with 40% DR. However, we observed differences in the effects of 10% and 40% DR on the incidence of fatal neoplasia; 40% DR resulted in a significant reduction in fatal neoplastic diseases, especially leukemia, which was the most common neoplastic disease in the rats.