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

Abstract

AbstractA 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 PSREDaphniafemales. 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 statementAdvances in aging studies revealed the need to extend the old-age health and functionality data from theDrosophila-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” inDaphnia– 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.