Mar 31, 2020

Development of an in vitro senescent hepatic cell model for metabolic studies in aging

BioRxiv : the Preprint Server for Biology
Bianca MoioliJin Zhou

Abstract

Although in vitro senescence models have been developed using primary fibroblasts, they may not be applicable for the study of metabolically active organs such as the liver. We thus developed an in vitro protocol to induce senescence in AML12 non-transformed hepatocyte cell lines derived from mice transgenic for transforming growth factor-alpha. Sequential oxidative stress with hydrogen peroxide-induced premature senescence in these cells as they exhibited molecular and metabolic signatures, had increased SA-{beta}Gal and {gamma}H2A.X staining and elevated senescence and pro-inflammatory gene expression that resembled the livers from aged mice. Metabolic phenotyping showed fuel switching towards more glycolysis, mitochondrial glutamine oxidation, and impaired energy production that also was similar to the livers from aged mice. Additionally, Senescence Activated Secretory Proteins (SASPs) sensitized normal AML12 cells to palmitate-induced toxicity, a known pathological effect of hepatic aging. In summary, we have generated an in vitro senescent AML12 cell model that not only show the molecular hallmarks of aging, but also recapitulates the aberrant metabolic phenotype found in aged liver. As such, they represent a novel and use...Continue Reading

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Mentioned in this Paper

Biological Markers
Gene Polymorphism
Genome-Wide Association Study
Study
Immune Response
Exons
Cd109 Gene (Procedure)
Genes
Candidate Disease Gene
Dysequilibrium Syndrome

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