The influence of metabolic rate on longevity in the nematode Caenorhabditis elegans.

Much of the recent interest in aging research is due to the discovery of genes in a variety of model organisms that appear to modulate aging. A large amount of research has focused on the use of such long-lived mutants to examine the fundamental causes of aging. While model organisms do offer many advantages for studying aging, it also critical to consider the limitations of these systems. In particular, ectothermic (poikilothermic) organisms can tolerate a much larger metabolic depression than humans. Thus, considering only chronological longevity when assaying for long-lived mutants provides a limited perspective on the mechanisms by which longevity is increased. In order to provide true insight into the aging process additional physiological processes, such as metabolic rate, must also be assayed. This is especially true in the nematode Caenorhabditis elegans, which can naturally enter into a metabolically reduced state in which it survives many times longer than its usual lifetime. Currently it is seen as controversial if long-lived C. elegans mutants retain normal metabolic function. Resolving this issue requires accurately measuring the metabolic rate of C. elegans under conditions that minimize environmental stress. Additionally, the relatively small size of C. elegans requires the use of sensitive methodologies when determining metabolic rates. Several studies indicating that long-lived C. elegans mutants have normal metabolic rates may be flawed due to the use of inappropriate measurement conditions and techniques. Comparisons of metabolic rate between long-lived and wild-type C. elegans under more optimized conditions indicate that the extended longevity of at least some long-lived C. elegans mutants may be due to a reduction in metabolic rate, rather than an alteration of a metabolically independent genetic mechanism specific to aging.