Chemical genetic screen identifies lithocholic acid as an anti-aging compound that extends yeast chronological life span in a TOR-independent manner, by modulating housekeeping longevity assurance processes
Citations Over TimeTop 10% of 2010 papers
Abstract
In chronologically aging yeast, longevity can be extended by administering a caloric restriction (CR) diet or some small molecules. These life-extending interventions target the adaptable target of rapamycin (TOR) and cAMP/protein kinase A (cAMP/PKA) signaling pathways that are under the stringent control of calorie availability. We designed a chemical genetic screen for small molecules that increase the chronological life span of yeast under CR by targeting lipid metabolism and modulating housekeeping longevity pathways that regulate longevity irrespective of the number of available calories. Our screen identifies lithocholic acid (LCA) as one of such molecules. We reveal two mechanisms underlying the life-extending effect of LCA in chronologically aging yeast. One mechanism operates in a calorie availability-independent fashion and involves the LCA-governed modulation of housekeeping longevity assurance pathways that do not overlap with the adaptable TOR and cAMP/PKA pathways. The other mechanism extends yeast longevity under non-CR conditions and consists in LCA-driven unmasking of the previously unknown anti-aging potential of PKA. We provide evidence that LCA modulates housekeeping longevity assurance pathways by suppressing lipid-induced necrosis, attenuating mitochondrial fragmentation, altering oxidation-reduction processes in mitochondria, enhancing resistance to oxidative and thermal stresses, suppressing mitochondria-controlled apoptosis, and enhancing stability of nuclear and mitochondrial DNA.
Related Papers
- → To Study the Relationship between Ergonomics & Efficiency of the Housekeeping Employees at Workplace(2016)2 cited
- → Synthetic studies of vitamin D3analogues from bile acids. Part 3. Syntheses of 1α,25-, 1α,24R-, and 1α,24S-dihydroxycholecalciferols from lithocholic acid and their biological activities(1979)8 cited
- → Dietary Bile Acids and Lipid Metabolism. V. Reversibility of the Effects of Lithocholic Acid in Chicks(1964)6 cited
- THE PROBLEMS FACED BY THE HOUSEKEEPINGDEPARTMENT OF NOVOTEL SOLO(2010)
- → Housekeeping Services: Hospital Ends Housekeeping Woes through in-depth Utilization Study(1971)