A test of the free-radical damage hypothesis of ageing and an evaluation of the effectiveness of dietary antioxidants
It has been suggested that elevation of an organism’s metabolic rate, such as cold exposure, will lead to an increase in reactive oxygen species (ROS) production. If this ROS production exceeds the antioxidant defence and repair mechanisms, oxidative stress will occur, particularly to proteins, lipids and DNA resulting in a decreased longevity. ROS scavengers, such as exogenous antioxidants, have been suggested as effective ‘anti-ageing’ strategies, and were expected to reverse the suggested increase in ROS production, caused by long-term cold exposure, and increase longevity. I sought to test these ideas in a novel small mammalian model, the short-tailed field vole, Microtus agrestis. Cold exposure caused the metabolic rate of voles to increase by approximately 50%. This was expected to cause an increase in oxidative damage, but contradictory to the ‘free radical’ theory of ageing there were no increases in oxidative lymphocyte or hepatocyte DNA damage or hepatic lipid peroxidation. In vole hepatocytes, with advancing age, lipid peroxidation decreased and the levels of endogenous antioxidants increased. Using electron spin resonance (ESR) the in vitro incubation of liver microsomes with an iron/ADP solution did not indicate an increase in lipid radical production either with age or cold exposure. The longevity of cold exposed voles was not significantly different to that of warm housed controls. The supplementation of voles with either a-tocopherol or ascorbic acid reduced lipid peroxidation and increased the levels of endogenous antioxidants compared to non-supplemented controls, but did not have any effect on oxidative lymphocyte DNA damage. There were no significant differences in the mean lifespans of supplemented voles compared to non-supplemented voles. This study indicates that the postulated link between metabolic rate and ageing may not be as tight as first thought, and that dietary antioxidants are ineffective in extending the lifespan of voles.