Assessing metabolic activity in aging Caenorhabditis elegans:: concepts and controversies

It is widely believed that normal by-products of oxidative metabolism and the subsequent molecular damage inflicted by them couple the aging process to metabolic rate. Accordingly, high metabolic rates would be expected to accelerate aging, and life-extending interventions are often assumed to act by attenuating metabolic rate. Notorious examples in Caenorhabditis elegans are food restriction, mutation in the Clock genes and several genes of the insulin-like signalling pathway. Here we discuss how metabolic rate can be accurately measured and normalized, and how to deal with differences in body size. These issues are illustrated using experimental data of the long-lived mutant strains clk-1(e2519) and daf-2(e1370). Appropriate analysis shows that metabolic rates in wildtype and in the clk-1 mutant are very similar. In contrast, the metabolic rate profiles point to a metabolic shift toward enhanced efficiency of oxidative phosphorylation in the daf-2 worms.