The search for the genetic basis of aging: the identification of gerontogenes in the nematode Caenorhabditis elegans

Abstract

Study of C. elegans has provided much information for gerontologists. The influence of the genome on life span is clearly observable, and at least one gerontogene, age-1, has been defined. Data relating to important evolutionary questions has emerged and will continue to be used in testing current hypotheses. We are using an approach unbiased by theoretical constraints to delineate aging processes simultaneously at the molecular and organismal levels. Much remains to be discovered before fundamental questions posed in this article are answered to a satisfactory degree. The immediate agenda is the identification and isolation of gerontogenes which influence life span in invertebrate models. This work is well in hand and will lead to the unraveling of specific life-span-determining processes. At this point we may be able to predict whether analogous processes also limit life in mammals. If we are fortunate and aging processes exhibit evolutionary conservation, many exciting possibilities await. Molecular tools provided by the invertebrate system can then be used to isolate homologous mammalian gerontogenes that could be subsequently utilized in highly targeted attempts to intervene in mammalian aging. This offers the most direct strategy for identifying life-span prolongation genes in humans.