Most animals, including humans, display sex-specific differences in lifespan but the causes for the differences are poorly studied. In C. elegans, an excellent model system to study aging, the focus has been largely on the hermaphrodites. Male lifespan was found to be shortened by male/male interactions, mating and male pheromones, thus requiring single male lifespan assays to uncover intrinsic male lifespan regulation. We are using a liquid assay in 96-well plates. This assay gains reproducible results, recapitulates the wild type aging experiments on plates, allows us to measure male lifespan without censoring large numbers of males, prevents interactions and is compatible with highly sensitive chemical analysis of ascarosides and other signaling molecules excreted by the worms. So far, we have used this assay to measure the effect of three aging paradigms: germline ablation, density/pheromone dependent lifespan shortening in males and dietary restriction. In contrast to hermaphrodites, male lifespan does not change significantly upon germline loss (either by ablation or glp-1 mutation). We also show that glp-1 hermaphrodites are thermo-tolerant (a trait often found in long-lived animals) while glp-1 males are not. We are profiling other traits of long-lived glp-1/ablated hermaphrodites such as DAF-16, SKN-1 and HLH-30 nuclear localization, expression of genes upregulated in glp-1 animals (QRT-PCR) and metabolic changes (fat storage). We find that glp-1 mutation, in contrast to hermaphrodites, does not dramatically increase fat storage in males suggesting this metabolic shift to increased fat storage is required. Finally, we find differences in levels of dafachronic acids in males and glp-1 hermaphrodites. In addition, we are also assessing contributions of specific tissue to sex-specific differences in lifespan using strains with sex-reversal in specific tissues. We find that intestinal masculinization abrogates the thermo-tolerance of glp-1 hermaphrodites indicating that a female intestine is required in the hermaphrodites for increased thermo-tolerance. However, glp-1 males with feminized intestines are not thermo-tolerant indicating that intestinal feminization is not sufficient to confer increased thermo-tolerance. Our analysis assesses how hormones, pheromones and tissues affect lifespan differently in C. elegans males and hermaphrodites and might shed light onto mechanisms that are conserved in other species as well.

Authors: Gordon, Sarah, McCulloch, Diana, Izrayelit, Yevgeniy, Gudibanda, Pooja, Antebi, Adam, Gems, David, Portman, Douglas, Schroeder, Frank, Rottiers, Veerle

Affiliations:
- Center for Neural Development and Disease, University of Rochester, Rochester, NY
- Max Planck Institute for Biology of Ageing, Cologne, Germany
- Boyce Thompson Institute and Department of Chemistry and Chemical Biology, Cornell University , Ithaca, NY
- Institute of Healthy Ageing, University College London, London, UK
- Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY
- Department of Nutritional Sciences & Toxicology, University of California Berkeley, Berkeley, CA