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Publication : Transcriptomic and metabolomic profiling of long-lived growth hormone releasing hormone knock-out mice: evidence for altered mitochondrial function and amino acid metabolism.

First Author  Hoffman JM Year  2020
Journal  Aging (Albany NY) Volume  12
Issue  4 Pages  3473-3485
PubMed ID  32091406 Mgi Jnum  J:302393
Mgi Id  MGI:6508242 Doi  10.18632/aging.102822
Citation  Hoffman JM, et al. (2020) Transcriptomic and metabolomic profiling of long-lived growth hormone releasing hormone knock-out mice: evidence for altered mitochondrial function and amino acid metabolism. Aging (Albany NY) 12(4):3473-3485
abstractText  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.
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