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.
