Mitochondria enable cellular respiration and their functions have been known to influence normal senescence as well as a range of aging-related diseases. Mitochondrial replacement therapy has been suggested to cure mitochondrial diseases by replacing pathogenic mitochondrial DNA. However, mitochondrial function relies on over 1,000 nuclear-encoded genes whose products function in the mitochondria. The interactions between mitochondrial and nuclear genomes (mito-nuclear interactions) are essential to mitochondrial performance, and thereby promote intergenomic coevolution. Tigriopus californicus is an emerging model for understanding mito-nuclear interactions because viable hybrids are easily generated in crosses between geographical populations with divergent mitochondrial sequences. It has also been proposed as an alternative model system for sex-specific studies due to the absence of sex chromosomes. Here we developed T. californicus as a new invertebrate model system to investigate sex-specific gene expression, the role of mitochondria in aging, and the effects of mito-nuclear interactions on sex-specific aging. In this study, two populations with 20.6% mitochondrial sequence divergence were crossed to produce two parental lines and two reciprocal F1 hybrids. For each cross, survivorship was measured over the full lifespan, and single-individual transcriptome sequencing was performed at 28 and 56 days post hatching. The findings will contribute to a better understanding of the mitochondrial basis of aging and the potential effects of mitochondrial replacement therapy on human health and aging in both sexes.