Mechanisms through which lithocholic acid delays yeast chronological aging under caloric restriction conditions
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Anthony Arlia-Ciommo1, Anna Leonov1, Karamat Mohammad1, Adam Beach1, Vincent R. Richard1, Simon D. Bourque1, Michelle T. Burstein1, Alexander A. Goldberg1, Pavlo Kyryakov1, Alejandra Gomez-Perez1, Olivia Koupaki1 and Vladimir I. Titorenko1
1Department of Biology, Concordia University, Montreal, Quebec, Canada
Vladimir I. Titorenko, email: firstname.lastname@example.org
Keywords: yeast; cellular aging; geroprotectors; lithocholic acid; metabolism
Received: August 15, 2018 Accepted: September 17, 2018 Published: October 09, 2018
All presently known geroprotective chemical compounds of plant and microbial origin are caloric restriction mimetics because they can mimic the beneficial lifespan- and healthspan-extending effects of caloric restriction diets without the need to limit calorie supply. We have discovered a geroprotective chemical compound of mammalian origin, a bile acid called lithocholic acid, which can delay chronological aging of the budding yeast Saccharomyces cerevisiae under caloric restriction conditions. Here, we investigated mechanisms through which lithocholic acidcan delay chronological aging of yeast limited in calorie supply. We provide evidence that lithocholic acid causes a stepwise development and maintenance of an aging-delaying cellular pattern throughout the entire chronological lifespan of yeast cultured under caloric restriction conditions. We show that lithocholic acid stimulates the aging-delaying cellular pattern and preserves such pattern because it specifically modulates the spatiotemporal dynamics of a complex cellular network. We demonstrate that this cellular network integrates certain pathways of lipid and carbohydrate metabolism, some intercompartmental communications, mitochondrial morphology and functionality, and liponecrotic and apoptotic modes of aging-associated cell death. Our findings indicate that lithocholic acid prolongs longevity of chronologically aging yeast because it decreases the risk of aging-associated cell death, thus increasing the chance of elderly cells to survive.
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