It is commonly assumed that there is a trade off between the pace of life and longevity, an assumption that is the basis for many theories of ageing. In a nutshell, it has long been observed in comparative studies that there is an inverse relationship between the rate of energy expenditure and lifespan of species. A candidate mechanism explaining this link is the oxidative stress theory of ageing, where damaging molecules, reactive oxygen species, are produced in proportion to metabolic rate, thereby damaging life's building blocks (nucleic acids, proteins, lipids) and shortening an individual's life. Luckily, protective and repair mechanisms exist and the balance between damage, protection and repair explains the extent of oxidative damage.
Despite extensive efforts in studying physiological mechanisms related to oxidative stress, the basic assumption linking metabolic rate and lifespan through oxidative damage remains unclear. To test the hypothesis that increased energy expenditure will induce greater oxidative damage and therefore reduce lifespan, Colin Selman, Jane McLaren and John Speakman from the University of Aberdeen and their colleagues from the Rowett Research Institute experimentally increased energy expenditure in short-tailed field voles by exposing them to the cold. By maintaining one group of voles at 22°C and another group of paired siblings at 7°C, the team managed to increase energy expenditure throughout the life of the cold-exposed group. It was then possible for the group not only to test the impact of increased energy expenditure on lifespan but also to monitor a collection of variables,such as oxidative stress indicators, levels of antioxidant molecules and the activity of antioxidant enzymes in a variety of tissues to see how the different life styles had affected the animals' physiology.
Exposing voles to the cold throughout most of their life increased energy use; all three measurements taken as an index of energy use (resting metabolic rate, daily energy expenditure and food intake) increased by approximately 50%or more. Even though a significant increase in energy expenditure was induced,the cold-exposed voles did not die younger than the warm-maintained group. Moreover, until late in their life the warm-exposed group had higher mortality risks than the cold-maintained voles. The fine details of the `live fast, die young' assumption may thus need further scrutiny as it does not appear to simply apply to this species.
To get a good grasp of the impact of metabolic rate variation on oxidative damage, the group measured various metabolic parameters. Indicators of oxidative damage on lymphocyte and hepatocyte DNA and hepatocyte lipids showed no effect of cold exposure in almost all cases, except a possible increase in damage to hepatocyte DNA. The team also monitored antioxidant molecule levels in the liver of these animals, and found no differences between the cold- and warm-exposed voles for the three antioxidants that they analysed. Moreover,the group measured the activity of three antioxidant enzymes in the heart,liver, kidney, muscle, duodenum and brown adipose tissue and only found a significant increase in superoxide dismutase in the cold vole's brown adipose tissue. So despite running at a higher metabolic rate, the team found no evidence of increased oxidative damage in the cold voles.
Together, this study shows that integrative approaches are necessary to test current hypotheses connecting metabolism and lifespan. An important increase in energy expenditure did not shorten lifespan or induce an obvious increase in oxidative damage in short-tailed field voles and it had little effect on antioxidant molecules and enzyme levels in most tissues. We have yet to establish when the `live fast, die young' rule applies.
