UC San Diego

The downregulation of ELOVL2, a fatty acid elongation enzyme, is associated with hallmarks of aging in multiple tissues. Currently, most work investigating the effects of the down regulation of ELOVL2 has only been conducted in the retina. However, given that previous research has demonstrated that ELOVL2 is highly expressed in the young liver, it is time to redirect attention and examine its effects in the liver during aging. The loss of ELOVL2 functionality in the aging liver is known to cause the dysregulation of major metabolic and inflammatory pathways that are needed to prevent liver diseases such as non-alcoholic fatty liver disease (NAFLD) and dysregulation of Il6 mediated signaling pathway. The aging liver is at a higher risk of multiple diseases including NAFLD, however, early state detection of fatty liver could ameliorate some of the symptoms caused by this disease. We aimed to create an accelerated aging liver model by knocking down ELOVL2 expression in a hepatic human cell line. By creating an accelerated aging liver model, we aimed to identify some of the major dysregulated genes during aging within the metabolic pathways involved in NASH. Through qPCR analysis it was possible to quantify the knockdown impact a small interfering RNA transfection treatment had in a hepatic cell line. Results indicated that siRNA transfection treatments worked the most efficiently to knockdown ELOVL2 and to mimic accelerated aging in the hepatic cells. Creating a model to observe the effects of loss of functionality of ELOVL2 in hepatic human cells may be the start of developing treatments to recover its functionality and ameliorate the effects of dysregulation in metabolic pathways involved in NASH, which affects about 25 percent of the adult U.S. population. Results were further extended by comparative analysis of gene expression in an Elovl2 mutant mouse line. Comparative analysis revealed that there was a significant increase in expression of IL6ST in the hepatic cell line, one of the main receptors involved in Il6 mediated signaling pathway. There was no significant change in gene expression for other observed genes such as MYC and STA1.