Transcriptomic and metabolomic profiling of long-lived growth hormone releasing hormone knock-out mice: evidence for altered mitochondrial function and amino acid metabolism
| Autor: | Liou Y. Sun, Jessica M. Hoffman, Stephen Barnes, William R. Swindell, Landon Wilson, Aliza Poonawalla, Mert Icyuz |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Longevity
metabolite Biology Growth Hormone-Releasing Hormone Transcriptome 03 medical and health sciences Mice transcriptomics 0302 clinical medicine Blood serum Metabolomics Downregulation and upregulation Adipose Tissue Brown Brown adipose tissue medicine Animals Amino Acids Insulin-Like Growth Factor I mouse 030304 developmental biology Mice Knockout 0303 health sciences aging Cell Biology Growth hormone–releasing hormone Phenotype Cell biology Mitochondria medicine.anatomical_structure Knockout mouse growth hormone Metabolome 030217 neurology & neurosurgery Research Paper |
| Zdroj: | Aging (Albany NY) |
| ISSN: | 1945-4589 |
| Popis: | Numerous genetic manipulations that extend lifespan in mice have been discovered over the past two decades, the most robust of which has arguably been the down regulation of growth hormone (GH) signaling. However, while decreased GH signaling has been associated with improved health and lifespan, many of the underlying physiological changes and molecular mechanisms associated with GH signaling have yet to be elucidated. To this end, we have completed the first transcriptomic and metabolomic study on long-lived growth hormone releasing hormone knockout (GHRH-KO) and wild-type mice in brown adipose tissue (transcriptomics) and blood serum (metabolomics). We find that GHRH-KO mice have increased transcript levels of mitochondrial and amino acid genes with decreased levels of extracellular matrix genes. Concurrently, mitochondrial metabolites are differentially regulated in GHRH-KO. Furthermore, we find a strong signal of genotype-by-sex interactions, suggesting the sexes have differing physiological responses to GH deficiency. Overall, our results point towards a strong influence of mitochondrial metabolism in GHRH-KO mice which potentially is tightly intertwined with their extended lifespan phenotype. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|