Aging and reproductive “rejuvenation” at a single nuclei resolution

Aging is a multifaceted process that occurs on the background of and is significantly driven by transcriptional and cell type abundance changes. Aging-related transcriptional changes may include reduced transcription of maintenance, repair and DNA methylation genes, de-differentiation, or increased transcription of transposons. Unbiased detection of these changes and full understanding of their physiological effects requires single-cell resolution. We studied single-nuclei transcriptomes of a model microcrustacean Daphnia magna sampled from 3 age- and reproductive status groups: young, old reproductively senescent, and old, regaining reproductive function late in life. We detected 17 cell clusters, some identifiable as ovary or fat body-, midgut-, epithelium-, and neural tissue-related, some escaping unambiguous identification. At the same time, some well-characterized cell types were not detected, such as hemocytes or myocytes. We detect significant changes of cell type abundance with age and with reproductive “rejuvenation” in ovary- and gut-related clusters. We also detect several patterns of functional transcriptional differences between age classes with nearly all cell types, with changes between old reproductive and old non-reproductive Daphnia often reversing age-related changes, and often in good concordance with previous bulk RNAseq data.