Exploring Multifunctional Markers of Biological Age in Farmed Gilthead Sea Bream (<em>Sparus aurata</em>). A Transcriptomic and Epigenetic Interplay for an Improved Fish Welfare Assessment Approach

Abstract

DNA-methylation clocks inform not only about chronological but also biological age, which brings a high resolution and precise understanding of age-related pathology and physiology. Attempts based on transcriptomic and epigenetic approaches arise as integrative biomarkers linking the quantification of stress response with a given fitness trait and may help to identify biological age markers, also considered welfare indicators. In gilthead sea bream, targeted gene expression and DNA-methylation analyses in white skeletal muscle proved sirt1 as a reliable marker of age-mediated changes of energy metabolism. To complete the list of welfare auditing biomarkers, wide-analyses of gene expression and DNA-methylation in one- and three-year old fish were combined. After discriminant analysis, 668 differentially expressed transcripts were matched with those containing differentially methylated (DM) regions (14,366), and 172 were overlapping. Through enrichment analyses and selection, two sets of genes were retained: 33 showing an opposite trend for DNA-methylation and expression, and 57 down-regulated and hypo-methylated. The first set displayed apparently a more reproducible and reliable pattern and 10 multifunctional genes with DM CpG in regulatory regions (sirt1, smad1, ramp1, psmd2 – up-regulated; col5a1, calcrl, bmp1, thrb, spred2, atp1a2 – down-regulated) were deemed candidate biological age markers for an improved welfare auditing in gilthead sea bream.