Metabolism and aging in the nematode Caenorhabditis elegans1,2

Abstract

Research into the causes of aging has greatly increased in recent years. Much of this interest is due to the discovery of genes in a variety of model organisms that appear to modulate aging. Studies of long-lived mutants can potentially provide valuable insights into the fundamental mechanisms of aging. While there are many advantages to the use of model organisms to study aging it is also important to consider the limitations of these systems, particularly because ectothermic (poikilothermic) organisms can survive a far greater metabolic depression than humans. As such, the consideration of only chronological longevity when assaying for long-lived mutants provides a limited perspective on the mechanisms by which longevity is increased. Additional physiological processes, such as metabolic rate, must also be assayed to provide true insight into the aging process. This is especially true in the nematode Caenorhabditis elegans, which has the natural ability to enter into a metabolically reduced state in which it can survive many times longer than its normal lifetime. 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 for aging.