Age-related analysis of transcriptome-wide sequencing of human liver

Background For the first time, transcriptome-wide analysis of human liver has been performed for demonstrating differences between young and old humans, identifying major age-related alterations in hepatic gene expression may pinpoint ontogenetic shifts with important hepatic and systemic consequences, provide novel pharmacogenetic information, and offer clues to more efficiently counteract symptoms of old age.

Methods We applied next-generation sequencing (NGS), normalized the expression strength to transcripts per million and carried out statistical (Mann-Whitney non-parametric test) and bioinformatic [by Ensemble Feature Selection (EFS) software] analysis. NGS results were exemplarily validated by quantitative real-time polymerase chain reaction (qRT-PCR).

Results Among 60,617 total and 19,986 protein-encoding transcripts, we identified 44 transcripts whose expressions highly significantly (p = 0.0003 to 0.0464) and most strikingly (EFS score >0.3: 16 transcripts; EFS score >0.2: 28 transcripts) differ between young and old livers. The genes encoding for 25 of these highly age-related transcripts could be assigned to the categories ‘regulome’, ‘inflammaging’, ‘regeneration’, and ‘pharmacogenes’, and two genes of interest did not match these categories. The differences were confirmed by qRT-PCR for 14 out of 16 selected transcripts. Our results have major implications in the area of ontogeny/aging and for the age-dependently increased occurrence of major diseases such as non-alcoholic fatty liver and steatohepatitis as well as hepatocellular carcinoma.

Conclusion Results of a transcriptome-wide analysis of human liver offer potential options towards developing future therapeutic interventions against major liver diseases and increased insight into key mechanisms underlying aging.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022