Live fast--live long? A commentary on a recent paper by Speakman et al.

Abstract

The recent paper by Speakman et al. (2004), ‘Uncoupled and surviving: individual mice with high metabolism have greater mitochondrial uncoupling and live longer’, is significant for two reasons. First, Speakman et al . demonstrate that within a cohort of mice there is a positive correlation between metabolic rate and longevity. This result is contrary to long-proposed theories of aging that inversely link energy expenditure to aging. Second, they provide a credible explanation for why such a positive correlation might exist: increased activation of uncoupling proteins may increase metabolic rates, but decrease the overall production of reactive oxygen species (ROS). As such, this research potentially provides an important contribution towards understanding and attenuating aging. The scientific origins of the concept that aging is inversely related to the rate of energy expenditure extend back nearly 100 years. In 1908 Rubner published results comparing metabolic rates in five species of mammals and concluded that despite large differences in their chronological longevity, these mammals had approximately equal, mass-specific (metabolic output standardized to a given body mass), lifetime energy output. These studies were expanded on by Pearl, who proposed the ‘rate of living hypothesis’, which directly linked the metabolic output of an organism to its longevity (Pearl, 1928). The causal mechanism linking these two was unclear, but Pearl proposed that the duration of life was determined by the exhaustion of a vital cellular component that was consumed at a rate proportional to the metabolic rate, with death occurring upon