Abstract

Dietary restriction appears to act as a general non-genetic mechanism that can robustly prolong lifespan. There have however been reports in many systems of cases where restricted food intake either shortens, or does not affect, lifespan. Here we analyze lifespan and the effect of food restriction via deprived peptone levels on lifespan in wild isolates and introgression lines (ILs) of the nematode Caenorhabditis elegans. These analyses identify genetic variation in lifespan, in the effect of this variation in diet on lifespan and also in the likelihood of maternal, matricidal, hatching. Importantly, in the wild isolates and the ILs, we identify genotypes in which peptone deprivation mediated dietary restriction reduces lifespan. We also identify, in recombinant inbred lines, a locus that affects maternal hatching, a phenotype closely linked to dietary restriction in C. elegans. These results indicate that peptone deprivation mediated dietary restriction affects lifespan in C. elegans in a genotype-dependent manner, reducing lifespan in some genotypes. This may operate by a mechanism similar to dietary restriction.

Highlights

  • Dietary restriction appears to act as a general non-genetic mechanism that can robustly prolong lifespan

  • To test if the genetic background affects the lifespan effects of peptone deprivation mediated dietary restriction (DR) we tested five introgression lines (ILs), each containing an introgressed portion of the CB4856 genome in an N2 genetic background that had previously been shown to affect lifespan[39]

  • Maternal hatching and the effect of peptone deprivation could be under balancing selection in nature, we studied these traits in 23 wild isolates and N2 (Figs 3 and 4; Supplementary Dataset 2)

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Summary

Introduction

Dietary restriction appears to act as a general non-genetic mechanism that can robustly prolong lifespan. We analyze lifespan and the effect of food restriction via deprived peptone levels on lifespan in wild isolates and introgression lines (ILs) of the nematode Caenorhabditis elegans These analyses identify genetic variation in lifespan, in the effect of this variation in diet on lifespan and in the likelihood of maternal, matricidal, hatching. Many ageing and most DR studies in C. elegans have avoided maternal hatching by assaying worms in the presence of 5-fluorodeoxyuridine (FUdR), a drug that inhibits cell division and prevents eggs from hatching This is potentially problematic when considering variation in the response to DR, as FUDR has been shown to affect lifespan in a genotype-dependent manner[31,32] and to interact with the stress response[33]. The genetics of variation in maternal hatching is poorly understood and a small number of quantitative trait loci (QTL) affecting maternal hatching have been identified[34], it is not known if these are related to variation in lifespan

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