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| Status |
Public on Nov 30, 2021 |
| Title |
Transcriptome-Wide Analysis of Human Liver Reveals Age-Related Differences in the Expression of Select Functional Gene Clusters and Evidence for a PPP1R10-Governed ‘Aging Cascade’. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
A transcriptome-wide analysis of human liver for demonstrating differences between young and old humans has not yet been performed. However, pinpointing major age-related alterations in hepatic gene expression may identify ontogenetic shifts with important hepatic and systemic con-sequences, provide novel pharmacogenetic information, offer clues to efficiently counteract symptoms of old age, and improve the overarching understanding of ontogeny and individual decline. By applying next-generation sequencing and subsequent statistical and bioinformatic [Ensemble Feature Selection (EFS)] analysis, we identified 44 transcripts among 60,617 total and 19,986 protein-encoding transcripts that significantly (p = 0.0003 to 0.0464; EFS score >0.3: 16 transcripts; EFS score >0.2: 28 transcripts) differ between young and old livers. Genes encoding for 25 of these highly age-related transcripts were assigned to the categories ‘regulome’, ‘in-flammaging’, ‘regeneration’, and ‘pharmacogenes’, plus two genes that did not match these cate-gories. Our results have major implications in the area of ontogeny/aging and for the age-dependently increased occurrence of non-alcoholic fatty liver, steatohepatitis, and hepatocellular carcinoma. In addition, we present a broadly substantiated and testable hypothesis on a genetical-ly governed ‘aging cascade’, wherein the protein phosphatase 1 regulatory subunit 10 (PPP1R10) gene acts as a putative ontogenetic master regulator, which is prominently flanked by the genes for the insulin-like growth factor-binding protein acid labile subunit (IGFALS) and dual specificity phosphatase 1 (DUSP1). The results of this transcriptome-wide analysis of human liver offer potential clues towards developing better therapeutic interventions against major liver diseases and increased insight into key mechanisms underlying aging.
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| Overall design |
Examination of differences in gene expression of human livers from 9 patients below age of 49 years and 8 patients older than 74 years.
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| Web link |
https://0-doi-org.brum.beds.ac.uk/10.3390/pharmaceutics13122009
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| |
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| Contributor(s) |
Schreiter T, Gieseler RK, Vílchez-Vargas R, Jauregui R, Sowa J, Klein-Scory S, Broering R, Croner RS, Treckmann JW, Link A, Canbay A |
| Citation(s) |
34959291 |
| Submission date |
Sep 10, 2021 |
| Last update date |
Mar 10, 2022 |
| Contact name |
Ramiro Vichez-Vargas |
| E-mail(s) |
ramiro.vilchez@med.ovgu.de
|
| Phone |
+493916724713
|
| Organization name |
Otto-von-Guericke-Universität Magdeburg
|
| Department |
Gastroenterology, Hepatology and infectious diseases
|
| Lab |
Molecular Gastroenterology and Microbiota-associated Diseases
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| Street address |
Leipzigerstr. 44
|
| City |
Magdeburg |
| State/province |
Saxony Anhalt |
| ZIP/Postal code |
39120 |
| Country |
Germany |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (17)
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| Relations |
| BioProject |
PRJNA762335 |
| SRA |
SRP336561 |
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