Chapter 1 - The Genetic Network of Life-Span Extension by Dietary Restriction

Abstract

This chapter focuses on the genetic pathways that mediate longevity induced by various dietary restriction (DR) regimens in Caenorhabditis elegans and provides evidence that these pathways are relatively independent, but interact to form a DR network. It also highlights the most conserved nodes of the DR network throughout species. C. elegans normally live in the soil and feed on bacteria, for example, those present on rotten fruits. One of the most commonly used methods to mimic DR is a genetic mutation (eat-2) that reduces the pharyngeal pumping rate of the worms, thereby leading to reduced nutrient consumption. In addition to this genetic way of inducing DR, there are four DR methods in which the source of nutrient is altered in liquid media. While liquid cultures are not the typical conditions for growing worms, they allow an easier manipulation of the nutrients. The most frequently used liquid method of DR, devised by Klass in 1977, consists in simply diluting E. coli bacteria in liquid cultures and has been termed bacterial DR (BDR). This BDR method has been further refined to include both a solid support and a liquid dilution of bacteria, and term this DR regimen LDR, for liquid DR. Finally, it provides possible explanations as to why distinct DR regimens trigger different genetic pathways to promote longevity and discusses how these different pathways might be harnessed to mimic DR.