Post-senescence reproductive rebound inDaphniaassociated with reversal of age-related transcriptional changes

A long-lived species of zooplankton microcrustaceans, Daphnia magna, sometimes exhibits late-life rebound of reproduction, briefly reversing reproductive senescence. Such events are often interpreted as terminal investment in anticipation of imminent mortality. We demonstrate that such post-senescence reproductive events (PSREs) neither cause not anticipate increased mortality. We analyze an RNAseq experiment comparing young, old reproductively senescent, and old PSRE Daphnia females. We first show that overall age-related transcriptional changes are dominated by the increase transcription of guanidine monophosphate synthases and guanylate cyclases, as well as two groups of presumed transposon-encoded proteins and by a drop in transcription of protein synthesis-related genes. We then focus on gene families and functional groups in which full or partial reversal of age-related transcriptional changes occur. This analysis reveals reversal, in the PSRE individuals, of age-related up-regulation of apolipoproteins D, lysosomal lipases, and peptidases and of age-related down-regulation of E3 ubiquitin kinases, V-type proton ATPases, and numerous proteins related to mitochondrial and muscle functions. While it is not certain which of these changes enable reproductive rejuvenation, and which are by-products of processes that lead to it, we present some evidence that post-senescence reproductive events are associated with the reversal of age-related protein and lipid aggregates removal, apoptosis, and with restoration of mitochondrial integrity. Significance statement Advances in aging studies revealed the need to extend the old-age health and functionality data from the Drosophila-C.elegans- yeast triad of model organisms to include those that combine the advantages of non-vertebrate models with stronger similarities to mammalian aging. This paper presents a previously unreported phenomenon: reproductive “rejuvenation” in Daphnia – a classic and a re-emerging choice model for longevity studies. These postsenescence reproductive episodes result in fecundity similar to that of young individuals and are accompanied by transcriptional shifts, often reverting age-related changes to youthful levels. Transcripts that show such reversal point to restoration of aggregate removal and of mitochondrial function. We believe that this finding opens a novel window of research towards mechanistic understanding of healthy aging.