Oncotarget

Research Papers:

Mechanisms through which lithocholic acid delays yeast chronological aging under caloric restriction conditions

Anthony Arlia-Ciommo, Anna Leonov, Karamat Mohammad, Adam Beach, Vincent R. Richard, Simon D. Bourque, Michelle T. Burstein, Alexander A. Goldberg, Pavlo Kyryakov, Alejandra Gomez-Perez, Olivia Koupaki, Vladimir I. Titorenko _

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Oncotarget. 2018; 9:34945-34971. https://doi.org/10.18632/oncotarget.26188

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Abstract

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

Correspondence to:

Vladimir I. Titorenko, email: vladimir.titorenko@concordia.ca

Keywords: yeast; cellular aging; geroprotectors; lithocholic acid; metabolism

Received: August 15, 2018    Accepted: September 17, 2018    Published: October 09, 2018

ABSTRACT

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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PII: 26188