Analysis of Different Strains of the Turquoise Killifish Identify Transcriptomic Signatures Associated With Heritable Lifespan Differences

Abstract

The African turquoise killifish Nothobranchius furzeri represents an emerging short-lived vertebrate model for aging research. Captive strains of this species are characterized by large differences in lifespan. To identify gene expression correlates of this lifespan differences, we analyzed a public transcriptomic dataset comprising 4 different tissues in addition to embryos. We focused on the GRZ and the MZM0410 captive strains, which show a near twofold difference in lifespan, but similar growth- and maturation-rates and validated the results in a newly generated dataset from a third longer-lived strain. The 2 strains show distinct transcriptome expression patterns already as embryos and the genotype has a larger effect than age on gene expression, both in terms of number of differentially expressed genes and magnitude of regulation. Network analysis detected RNA processing and histone modifications as the most prominent categories upregulated in GRZ. This strain also showed idiosyncratic expression patterns, such as high expression of DND is somatic tissues and transcriptional aging signatures already at sexual maturity (anticipated aging) in all 4 tissues, suggesting that short lifespan is the results of events that occur early in life rather than the progressive accumulation of strain-dependent differences. The GRZ strain is the most commonly used N furzeri strain in intervention studies and our results warrant replication of at least key findings in longer-lived strains.

Keywords: Aging; Animal model; Genetics; Killifish; Systems biology.