Abdulkadir ÇOBAN, Abdullah OLGUN, Zeynep KÖKSAL

The effect of reducing Endoplasmic reticulum stress by Tauroursodeoxycholic acid on Caenorhabditis elegans lifespan

Endoplasmic reticulum (ER) stress is involved in many diseases including diabetes, cancer and aging. Tauroursodeoxycholic acid (TUDCA) is a chemical chaperone that reduces ER stress. Caenorhabditis elegans (C. elegans), a widely used model organism in aging studies, also suffers from ER stress. In this study, we tested the effect of TUDCA on C. elegans life span with the aim to decipher the contribution of ER stress on C. elegans aging. We tested TUDCA at the concentrations of 0.625, 1.25, 2.5, 3.75, 5, 7.5, 10, 15 and 20 mM. It showed a negative effect on the life span at all of the tested concentrations except 3.75 mM. At this concentration it had no toxicity nor an effect on longevity. One of the previously reported critical micellar concentrations (CMC) of TUDCA is closer to this concentration. Therefore TUDCA’s mechanism of action could be explained, at least in part, by its micelle formation. It could have exerted negative effects at both lower and higher concentrations than CMC. If it had a positive effect on life span through ameliorating ER stress at the CMC, this could have been neutralized by its partial toxicity. Our results can be helpful in future studies on TUDCA which is a very important and promising therapeutical agent.

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