The `free radical' theory of ageing, which relates to the production of harmful, lifetime-reducing reactive oxygen species, currently receives much attention. This hypothesis suggests that animals live longer when they reduce their caloric intake, because the associated drop in their metabolic rate leads to a decreased production of reactive oxygen species. Thus, to disentangle the relationship between metabolic rate and reactive oxygen species, experiments involving food-restricted animals are necessary. But, as animals also lose weight during fasting, an important question is whether caloric restriction directly affects metabolism or, alternatively, whether any changes in metabolic rate may simply be attributed to weight loss and different organ composition in thinner animals.
To address this issue, Colin Selman from the Department of Aging and Geriatric Research at the University of Florida and his colleagues in Florida and Scotland investigated the energy expenditure and body morphology of well-fed and food-restricted Fischer rats. The team expected caloric restriction to result in a drop in the rodents' metabolic rate. Restricting the food intake of 12 young and old rats by 40%, they tried to uncover how caloric restriction, and thus a lowered metabolic rate, affects the ageing process. Simultaneously, they measured total daily energy expenditure using the doubly labelled water method both in ad libitum-fed and food-restricted rats from the two age classes. To assess the impact of morphology and lean tissue mass on the rats' total energy budgets, the team sacrificed all the rats and performed intensive organ morphometric analyses.
As expected, Selman and his colleagues found that food-restricted rats expended less energy than their well-fed conspecifics. However, this was only the case for 6-month-old juveniles. The team was surprised to find that older food-restricted rats (aged 26 months) expended just as much energy as their ad libitum-fed counterparts of the same age. Selman and his team attributed this to the fact that the ad libitum food intake of elderly rats declined from the beginning of the food intake measurements until the end of the experiment, so that they ended up eating about the same amount as the food-restricted rats. Thus, the energy expenditure of well-provisioned rats was not different from that of undernourished rats. The authors generated an interesting model to predict the energy demands of rats with different food intakes, based on the rats' morphological variation, and compared these predicted energy demands with their observed data. They found that food-restricted rats spent significantly more energy than the authors predicted from the rats' altered morphology. Selman and his colleagues concluded that both young and old underfed rats have a significantly increased metabolic rate when taking into account the rats' altered body condition.
At first sight, these results contradict the free radical theory of ageing,as old rats with high levels of energy expenditure presumably have to cope with more free radicals. Since previous studies on mice and dogs have revealed that increased energy expenditure is associated with increased longevity, the authors suggest that the free radical theory of ageing should be reassessed. Can fasting rats provide us with clues to the secret of a longer life?