Dietary Restriction (DR) in C. elegans: Identify genes that interact with DR and modulate its affect on lifespan

Specific Aims

Dietary restriction (DR), which can be defined as a reduction in nutrient intake without malnutrition, has been reported to extend lifespan in a diverse array of evolutionarily divergent species, including yeast, nematodes, fruit flies, mice, fish, spiders, rodents and rhesus monkeys. The primary goals of this project are to utilize the nematode C.elegans to better understand the interaction among components of this pathway with respect to longevity control and identify causal mechanisms of lifespan extension downstream of dietary restriction.

Project Introduction

The nematode C. elegans has been used extensively to study the biology of aging, and several determinants of C. elegans longevity are observed in higher order organisms. The specific mechanisms of longevity in C. elegans have not been completely identified and many pathways are still poorly understood. Dietary restriction is one promising pro-longevity intervention, though like other aspects of longevity, its mechanism is also poorly defined. DR, a reduction in caloric intake without malnutrition, extends lifespan and has been found to delay the onset of age-associated disease, not only in C. elegans, but in a wide range of species including yeast, flies, mice, and primates. We are performing a genome-wide screen of the Vidal RNA interference (RNAi) Library, which has a catalog of 11,511 clones (10,953 genes, targeted by 11,511 RNAi clones; due to overlapping genes). By knocking down specific genes within the C. elegans genome through RNAi, we are able to observe an extension or reduction in longevity in response to DR. After cutting off the genes with a 70% survival rate using liquid culture, and checking candidate genes’ lifespan using solid culture. We will follow up on our collected data by measuring the full lifespans of all mutants that respond strongly in the screen. By screening such a large number of genes, the widespread effect, and hopefully, mechanism of DR will be elucidated. We hope to see genes significantly affected by DR cluster into groups with common functionality, or along the same pathway, and then follow up on those specific pathways to clarify the mechanisms underlying DR. If these pathways are discovered, research findings relating to C. elegans may be applicable to other organisms. We hope to confirm these results and further investigate the interaction between DR and other potential longevity pathways.

DR team: Haeri Choi, Shannon Klum, Marissa Simko, Heather Schneider