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.

Aging
Alexander A GoldbergVladimir I Titorenko

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 suppressi...Continue Reading

References

Dec 1, 2004·Aging Cell·Daniel Amador-NoguezGretchen Darlington
May 17, 2005·Mechanisms of Ageing and Development·David A Sinclair
Aug 2, 2005·Cell Metabolism·Sebastian GrönkeRonald P Kühnlein
Sep 3, 2005·FEMS Yeast Research·Choon Pei LowHongyuan Yang
Apr 22, 2006·Aging Cell·Donald K IngramRafael deCabo
May 22, 2007·Ageing Research Reviews·Matt Kaeberlein, R Wilson Powers
May 25, 2007·Aging Cell·Daniel Amador-NoguezGretchen Darlington
Aug 9, 2007·Nature Reviews. Molecular Cell Biology·Steven J Russell, C Ronald Kahn
Aug 19, 2007·Nature Reviews. Molecular Cell Biology·Marco GiorgioPier Giuseppe Pelicci
Sep 13, 2007·Nature Reviews. Molecular Cell Biology·Benoît D'Autréaux, Michel B Toledano
Mar 5, 2008·Cell Metabolism·David Gems, Linda Partridge
Aug 2, 2008·Nature Reviews. Drug Discovery·Charles ThomasKristina Schoonjans
Oct 31, 2008·Cell Cycle·Mikhail V Blagosklonny
May 15, 2009·Ageing Research Reviews·David A Sinclair, Philipp Oberdoerffer
Jun 6, 2009·Ageing Research Reviews·Lydia W S Finley, Marcia C Haigis
Nov 20, 2009·Cell Cycle·Mikhail V Blagosklonny

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Citations

Oct 14, 2011·Oncotarget·Alexander A GoldbergVladimir I Titorenko
Jun 22, 2011·Digestive Diseases·Thijs W H PolsKristina Schoonjans
Dec 7, 2013·Cell Cycle·Luis A RokeachDominic Dulude
Apr 15, 2015·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Anna LeonovVladimir I Titorenko
Sep 23, 2014·International Journal of Molecular Sciences·Anthony Arlia-CiommoVladimir I Titorenko
May 8, 2015·Cell Cycle·Troy A A Harkness
Jun 16, 2018·FEMS Yeast Research·Andreas ZimmermannDidac Carmona-Gutierrez
Jul 28, 2019·Aging·Mélanie ViltardGérard Friedlander
Mar 5, 2013·Oncotarget·James A McCubreyZoya N Demidenko
Jul 21, 2010·Aging·Troy A Harkness
Jul 3, 2013·IUBMB Life·Anna Leonov, Vladimir I Titorenko
Jun 28, 2014·Applied Microbiology and Biotechnology·Ziyun WuDejian Huang
Oct 11, 2017·Cellular Oncology (Dordrecht)·Trang H LuuHassan Nazih
Jun 9, 2017·Oxidative Medicine and Cellular Longevity·Younes MedkourVladimir I Titorenko
Apr 11, 2018·Oxidative Medicine and Cellular Longevity·Karamat MohammadVladimir I Titorenko
Nov 19, 2010·Traffic·Vladimir I Titorenko, Stanley R Terlecky
Oct 15, 2013·FEMS Yeast Research·Tobias Eisenberg, Sabrina Büttner
Dec 9, 2014·Cell Cycle·Vincent R RichardVladimir I Titorenko
Mar 23, 2017·Aging·Tatiana Iouk, Vladimir I Titorenko
Jan 9, 2014·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Yuancai LiuDejian Huang
Oct 27, 2016·Aging·Pavlo KyryakovVladimir I Titorenko
Jan 17, 2016·Annual Review of Food Science and Technology·Susan A Joyce, Cormac G M Gahan
Jun 2, 2017·Natural Products and Bioprospecting·Ai-Jun DingHuai-Rong Luo
Jun 13, 2013·Aging Cell·Sophie D LefevreIda J van der Klei
Aug 29, 2012·Oxidative Medicine and Cellular Longevity·Júlia SantosMaria João Sousa
Feb 10, 2012·PLoS Genetics·Xinhe HuangRobert C Dickson
Apr 27, 2012·Rejuvenation Research·Jens Krøll
Jul 23, 2016·Oncotarget·Vicky LutchmanVladimir I Titorenko

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Methods Mentioned

BETA
fluorescence microscopy

Software Mentioned

eMolecules

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