Dietary restriction in rodents--delayed or retarded ageing?

Dietary restriction (DR) feeding increases survival significantly in strains of rats and mice. There remains however, the question as to whether these two species are always responding in an identical manner to the feeding regime. Enhanced survival can be achieved either through a set-point effect, where there is a change in the elevation of the Ln age-specific mortality rate or, by a decrease in the slope of the Ln age-specific mortality rate that results in a significant increase in the time to double the rate of mortality. It is only the second response that is evidence of a slower rate of ageing. These two possible responses to DR feeding may confound attempts to identify the biochemical mechanisms underlying the effect of DR on survival. A general lack of consistency is evident in the data and this is apparent when evaluating the free radical hypothesis of ageing in this model. Further, this hypothesis as currently viewed may be too simplistic to explain the variety and complexity of the ageing phenotype. What may be more important is not oxidative macromolecular damage but the slow transition to this cellular endpoint through the slow development of oxidative stress and the role it plays in modifying cell gene expression profiles.