Researchers: 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
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 acid can 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.
References
- Lessons on longevity from budding yeast.
- Small molecule SIRT1 activators for the treatment of aging and age-related diseases.
- Small-molecule allosteric activators of sirtuins.
- Geroprotectors.org: a new, structured and curated database of current therapeutic interventions in aging and age-related disease.
- Developing criteria for evaluation of geroprotectors as a key stage toward translation to the clinic.
- Geroprotectors: A Unified Concept and Screening Approaches.
- Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes.