Blackwell, Thomas KeithKaragodsky, Natalie2014-06-062014-06-062014Karagodsky, Natalie. 2014. Dietary Restriction-Induced Longevity in Caenorhabditis elegans: Mediated by Stress Defense, NAD\(^+\)-Dependent Mechanisms and a Respiratory Shift. Doctoral dissertation, Harvard University.http://dissertations.umi.com/gsas.harvard:11651http://nrs.harvard.edu/urn-3:HUL.InstRepos:12274307Dietary restriction (DR), or the reduction of food consumption without malnutrition, is the most conserved method of preventing or reversing age associated diseases. It is also the most conserved method of increasing lifespan, across model organisms. We developed a robust liquid DR method for C. elegans, to investigate requirements for stress defense and NAD\(^+\)-associated mechanisms in mediating DR induced longevity. We found that DR lifespan extension depended upon stress defense regulators that act downstream of TORC1 and growth pathways, as well as SIR-2.1/SIRT1 and the NAD\(^+\) salvage pathway enzyme PNC-1. Surprisingly, PNC-1 was not required for improvement in two measures of healthspan, or the period of life spent free from disease. This suggests that the genetic regulation of DR effects can be uncoupled from one another, and that increased healthspan does not always indicate increased lifespan.en-USMolecular biologyGeneticsagingdietary restrictionC. elegansNAD+sirtuinsstress defenseThesis or Dissertation