TY  - GEN
T1  - Caenorhabditis Intervention Testing Program: the farnesoid X receptor agonist obeticholic acid does not robustly extend lifespan in nematodes
AU  - Morshead, Mackenzie L
AU  - Sedore, Christine A
AU  - Jones, E Grace
AU  - Hall, David
AU  - Plummer, W Todd
AU  - Garrett, Theo
AU  - Lucanic, Mark
AU  - Guo, Max
AU  - Driscoll, Monica
AU  - Phillips, Patrick C
AU  - Lithgow, Gordon
DO  - 10.17912/micropub.biology.000257
UR  - http://beta.micropublication.org/journals/biology/micropub-biology-000257/
AB  - The Caenorhabditis Intervention Testing Program (CITP) is a multi-institutional, National Institute on Aging (NIA)-funded consortium. The goal of the program is to identify chemical compounds that extend lifespan robustly and reproducibly across genetically diverse Caenorhabditis strains (Lucanic et al. 2017). The CITP test compounds are selected if they are consistently highly ranked via computational prediction for lifespan or healthspan effects (Coleman-Hulbert et al. 2019), if they are predicted or known to interact with known lifespan-regulating pathways, or if they have previously been reported as extending lifespan or healthspan in laboratory animals. Obeticholic acid is an analog of the natural bile acid chenode oxycholic acid, which acts as an agonist of the farnesoid X receptor (FXR) (Neuschwander-Teri et al. 2015), a nuclear receptor (NR) closely involved with hepatic triglyceride homeostasis. Obeticholic acid is most commonly used to treat the autoimmune liver disease, primary biliary cholangitis. The most likely homolog of FXR in C. elegans is DAF-12, which can bind and be activated by human bile acids (Held et al. 2006; Zhi et al. 2011). DAF-12 modulation is of particular interest because it is closely linked to dauer formation, lifespan extension, and metabolism homeostasis (Antebi 2015).
PY  - 2020
JO  - microPublication Biology
ER  -