Effects of dietary restriction in a new invertebrate model for sex-specific aging

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Project Summary Dietary restriction (DR) has been shown to increase lifespan in a wide range of organisms including yeast, nematodes, fruitflies, mice and humans. However, fairly little is known about how DR effects on aging differ between sexes. Further, while mitochondrial function is central to our understanding of dietary effects on lifespan, the impact of alternative mitochondrial haplotypes (mitotypes) on the success of DR intervention have been explored in only a limited number of taxa. The proposed project addresses these questions using a new invertebrate model for aging, the copepod Tigriopus californicus. This species is well suited to assessing mitochondrial and mitonuclear impacts on aging, because viable and fertile hybrids are easily produced in crosses between populations with tremendously divergent mitochondrial DNA (mtDNA). Further, because the species lacks sex chromosomes, sex specific mitochondrial effects are not confounded with the effects of sex chromosomes. Importantly, the species shows dramatic sex differences in features that may impact the success of DR, with females raised under control conditions having shorter lifespan, higher stress tolerance, higher mtDNA content, lower 8-OH-dG DNA damage, lower expression of genes involved in oxidative phosphorylation and higher expression of genes involved in mitochondrial biogenesis. Because effects of DR on aging have never been investigated in this species, this pilot study first tests the effects of a series of restricted food rations on sex-specific lifespan. And because the success of DR may vary with mitotype, assays will be done on three different mitotypes placed onto the same nuclear background. As a preliminary test of the functional consequences of DR, lines will be assayed for mitochondrial copy number and DNA damage in both sexes. By providing foundational data on the response of T. californicus to dietary restriction, this project will pave the way for future work on this species aimed at understanding mechanisms of sex-specific mitochondrial response to DR.