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

Int J Mol Sci. 2024 Sep 11;25(18):9836. doi: 10.3390/ijms25189836.

Abstract

DNA methylation clocks provide information not only about chronological but also biological age, offering 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 responses with specific fitness traits and may help identify biological age markers, which are 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 in 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 an apparently 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 improved welfare auditing in gilthead sea bream.

Keywords: DNA methylation; biological age; chronological age; epigenetics; fish welfare; transcriptomics.

MeSH terms

  • Aging / genetics
  • Animal Welfare
  • Animals
  • Biomarkers*
  • DNA Methylation*
  • Epigenesis, Genetic*
  • Gene Expression Profiling
  • Sea Bream* / genetics
  • Sea Bream* / metabolism
  • Transcriptome*

Substances

  • Biomarkers

Grants and funding

This study forms part of the ThinkInAzul program and was supported by MCIN with funding from European Union NextGenerationEU (PRTR-17.I1) and by Generalitat Valenciana (THINKINAZUL/2021/024) to JP-S. Additional funding was obtained by the Spanish MCIU project BreamHOLOBIONT (PID2023-146990OB-I00).