Rachel Samson
Pronouns:
Research Mentor(s): Gonzalo Garcia
Research Mentor School/College/Department: Pathology / Medicine
Program:
Authors: Rachel Samson, Jiexian Chen, Joshua Berg, Gonzalo Garcia, Gonzalo Garcia, Richard Miller
Session: Session 3: 11:00 am – 11: 50 am
Poster: 6
Abstract
Intervention drugs in food such as Rapamycin, Acarbose, and Canagliflozin have shown to extend lifespan in mice. Studies of these interventions showed a decline in the extracellular signal-regulated kinase (ERK) signaling pathway. In addition to these signaling changes, there was also a reduction in the levels of enzymes responsible for fat metabolism in liver cells. The underlying mechanism that links lifespan extension and declines in enzymes related to fat metabolism are unknown. We hypothesize that lifespan extension in all of these interventions is mediated by a shared mechanism — reduction in ERK signaling leading to a reduction in fat enzymes. To test the hypothesis, mouse hepatocyte cell lines (AML) were treated with Trametinib, a drug that inhibits the first step of the ERK signaling pathway (MEK1/2, poster figure 1). Western blot analysis showed a reduction in levels of proteins associated with fat enzymes by Trametinib treatments. The data suggested that reduction of ERK1/2 signaling may be responsible for changes in fat metabolism. Since this was seen in vivo with the intervention diets and in vitro with the use of Trametinib, reduction of MEK1/ERK pathway may result in extension of lifespan in mice. Therefore, we have identified one possible underlying cellular mechanism related to ERK signaling that may be key for lifespan extension.
