A screen of small molecule and genetic modulators of life span in female Drosophila identifies etomoxir, RH5849 and unanticipated temperature effects

References

• Baulieu EE. RU 486 (mifepristone). A short overview of its mechanisms of action and clinical uses at the end of 1996. Ann N Y Acad Sci. 1997;828(1 Uterus, The):47–58. Epub 1997/11/05. PubMed PMID: 9329823.
   PubMedGoogle Scholar
• Chen J, Wang J, Shao J, et al. The unique pharmacological characteristics of mifepristone (RU486): from terminating pregnancy to preventing cancer metastasis. Med Res Rev. 2014;34(5):979–1000. PubMed PMID: 24585714.
   PubMed Web of Science ®Google Scholar
• Gross C, Blasey CM, Roe RL, et al.Mifepristone reduces weight gain and improves metabolic abnormalities associated with risperidone treatment in normal men.Obesity (Silver Spring).2010;18(12):2295–2300. Epub 2010/03/27. PubMed PMID: 20339369
   PubMed Web of Science ®Google Scholar
• Bernal-Sore I, Navarro-Marquez M, Osorio-Fuentealba C, et al. Mifepristone enhances insulin-stimulated Akt phosphorylation and glucose uptake in skeletal muscle cells. Mol Cell Endocrinol. 2018;461:277–283. Epub 2017/09/26. PubMed PMID: 28943275.
   PubMed Web of Science ®Google Scholar
• Gubbi S, Muniyappa R, Sharma ST, et al.Mifepristone improves adipose tissue insulin sensitivity in insulin resistant individuals.J Clin Endocrinol Metab.2021;106(5):1501–1515. Epub 2021/01/29. PubMed PMID: 33507248; PMCID: PMC8063260
   PubMed Web of Science ®Google Scholar
• Lin S, Han Y, Shi Y, et al.Revealing a steroid receptor ligand as a unique PPARgamma agonist.Cell Res.2012;22(4):746–756. Epub 2011/10/12. PubMed PMID: 21986665; PMCID: PMC3257359
   PubMed Web of Science ®Google Scholar
• Wu XJ, Sun XH, Wang SW, et al.Mifepristone alleviates cerebral ischemia-reperfusion injury in rats by stimulating PPAR gamma.Eur Rev Med Pharmacol Sci.2018;22(17):5688–5696. Epub 2018/09/20. PubMed PMID: 30229846
   PubMed Web of Science ®Google Scholar
• Hashimoto T, Igarashi J, Hasan AU, et al.Mifepristone promotes adiponectin production and improves insulin sensitivity in a mouse model of diet-induced-obesity.PLoS One.2013;8(11):e79724. Epub 2013/11/14. PubMed PMID: 24223187; PMCID: PMC3819252
   PubMed Web of Science ®Google Scholar
• Janani C, Ranjitha Kumari BD. PPAR gamma gene–a review.Diabetes Metab Syndr.2015;9(1):46–50. Epub 2014/12/03. PubMed PMID: 25450819
   PubMed Web of Science ®Google Scholar
• Zhang X, Zhang B, Peng B, et al. Different Dose of sucrose consumption divergently influences gut microbiota and PPAR-gamma/MAPK/NF-kappaB pathway in DSS-induced colitis mice. Nutrients. 2022;14(13). Epub 2022/07/10. PubMed PMID: 35807944; PMCID: PMC9268685 doi:10.3390/nu14132765
   Web of Science ®Google Scholar
• Celinski K, Dworzanski T, Fornal R, et al. Comparison of the anti-inflammatory and therapeutic actions of PPAR-gamma agonists rosiglitazone and troglitazone in experimental colitis. J Physiol Pharmacol. 2012;63(6):631–640. Epub 2013/02/08. PubMed PMID: 23388479.
   PubMed Web of Science ®Google Scholar
• Waite LL, Person EC, Zhou Y, et al.Placental peroxisome proliferator-activated receptor-gamma is up-regulated by pregnancy serum.J Clin Endocrinol Metab.2000;85(10):3808–3814. Epub 2000/11/04. PubMed PMID: 11061543
   PubMed Web of Science ®Google Scholar
• Chandra A, Kaur P, Sahu SK, et al. A new insight into the treatment of diabetes by means of pan PPAR agonists. Chem Biol Drug Des. 2022. Epub 2022/01/07. PubMed PMID: 34990085. doi: 10.1111/cbdd.14020
   Web of Science ®Google Scholar
• Zipper L, Jassmann D, Burgmer S, et al. Ecdysone steroid hormone remote controls intestinal stem cell fate decisions via the PPARgamma-homolog Eip75B in Drosophila. eLife. 2020;9. Epub 2020/08/11. PubMed PMID: 32773037; PMCID: PMC7440922. doi: 10.7554/eLife.55795.
   PubMed Web of Science ®Google Scholar
• Ahmed SMH, Maldera JA, Krunic D, et al.Fitness trade-offs incurred by ovary-to-gut steroid signalling in Drosophila.Nature.2020;584(7821):415–419. Epub 2020/07/10. PubMed PMID: 32641829; PMCID: PMC7442704
   PubMed Web of Science ®Google Scholar
• Eggleton JS, Jialal I. Thiazolidinediones. StatPearls. Treasure Island (FL) 2020.
   Google Scholar
• White MA, Wolfner MF. The effects of male seminal fluid proteins on gut/gonad interactions in Drosophila.Insects.2022;13(7):623. Epub 2022/07/28. Epub 2022/07/28.
   PubMed Web of Science ®Google Scholar
• White MA, Bonfini A, Wolfner MF, et al. Drosophila melanogaster sex peptide regulates mated female midgut morphology and physiology. Proc Natl Acad Sci U S A. 2021;118(1). Epub 2021/01/15. PubMed PMID: 33443193; PMCID: PMC7817148 doi:10.1073/pnas.2018112118
   Web of Science ®Google Scholar
• Sieber MH, Spradling AC. Steroid signaling establishes a female metabolic state and regulates SREBP to control oocyte lipid accumulation.Curr Biol.2015;25(8):993–1004. Epub 2015/03/25. PubMed PMID: 25802149
   PubMed Web of Science ®Google Scholar
• Reiff T, Jacobson J, Cognigni P, et al. Endocrine remodelling of the adult intestine sustains reproduction in Drosophila. eLife. 2015;4:e06930. PubMed PMID: 26216039; PMCID: PMC4515472.
   PubMed Web of Science ®Google Scholar
• Morris BO, Jasper H. Reactive oxygen species in intestinal stem cell metabolism, fate and function. Free Radic Biol Med. 2021;166:140–146. Epub 2021/02/19. PubMed PMID: 33600942.
   PubMed Web of Science ®Google Scholar
• Zwick RK, Ohlstein B, Klein OD. Intestinal renewal across the animal kingdom: comparing stem cell activity in mouse and Drosophila.Am J Physiol Gastrointest Liver Physiol.2019;316(3):G313–G22. Epub 2018/12/14. PubMed PMID: 30543448; PMCID: PMC6415738
   PubMed Web of Science ®Google Scholar
• Zhang P, Holowatyj AN, Ulrich CM, et al.Tumor suppressive autophagy in intestinal stem cells controls gut homeostasis.Autophagy.2019;15(9):1668–1670. Epub 2019/06/20. PubMed PMID: 31213134; PMCID: PMC6693466
   PubMed Web of Science ®Google Scholar
• Tower J, Landis GN, Shen J, et al. Mifepristone/RU486 acts in Drosophila melanogaster females to counteract the life span-shortening and pro-inflammatory effects of male sex peptide. Biogerontology. 2017;18(3):413–427. PubMed PMID: 28451923; PMCID: PMC5507676.
   PubMed Web of Science ®Google Scholar
• Landis GN, Salomon MP, Keroles D, et al. The progesterone antagonist mifepristone/RU486 blocks the negative effect on life span caused by mating in female Drosophila. Aging (Albany NY). 2015;7(1):53–69. PubMed PMID: 25614682; PMCID: PMC4350324.
   PubMedGoogle Scholar
• Landis GN, Doherty DV, Yen CA, et al.Metabolic signatures of life span regulated by mating, sex peptide, and mifepristone/Ru486 in female Drosophila melanogaster.J Gerontol A Biol Sci Med Sci.2021;76(2):195–204. Epub 2020/07/11. Epub 2020/07/11
   PubMed Web of Science ®Google Scholar
• Landis GN, Hilsabeck TAU, Bell HS, et al. Mifepristone increases life span of virgin female Drosophila on regular and high-fat diet without reducing food intake. Front Genet. 2021;12:751647. Epub 2021/10/19. Epub 2021/10/19.
   PubMed Web of Science ®Google Scholar
• Landis GN, Riggan L, Bell HS, et al. Mifepristone increases life span in female Drosophila without detectable antibacterial activity. Front Aging. 2022;3:924957. Epub 2022/08/09. Epub 2022/08/09.
   PubMedGoogle Scholar
• Loch G, Zinke I, Mori T, et al.Antimicrobial peptides extend lifespan in Drosophila.PLoS One.2017;12(5):e0176689. Epub 2017/05/19. PubMed PMID: 28520752; PMCID: PMC5435158
   PubMed Web of Science ®Google Scholar
• Sun J, Tower J. FLP recombinase-mediated induction of Cu/Zn-superoxide dismutase transgene expression can extend the life span of adult Drosophila melanogaster flies. Mol Cell Biol. 1999;19(1):216–228. PubMed PMID: 9858546.
   PubMed Web of Science ®Google Scholar
• Ren C, Finkel SE, Tower J. Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity. Exp Gerontol. 2009;44(3):228–235. PubMed PMID: 18955126.
   PubMed Web of Science ®Google Scholar
• Ren C, Webster P, Finkel SE, et al. Increased internal and external bacterial load during Drosophila aging without life-span trade-off. Cell Metab. 2007;6(2):144–152. PubMed PMID: 17681150.
   PubMed Web of Science ®Google Scholar
• McGuire SE, Le PT, Osborn AJ, et al. Spatiotemporal rescue of memory dysfunction in Drosophila. Science. 2003;302(5651):1765–1768. PubMed PMID: 14657498.
   PubMed Web of Science ®Google Scholar
• Antonello ZA, Reiff T, Ballesta-Illan E, et al.Robust intestinal homeostasis relies on cellular plasticity in enteroblasts mediated by miR-8-Escargot switch.EMBO J.2015;34(15):2025–2041. Epub 2015/06/17. PubMed PMID: 26077448; PMCID: PMC4551350
   PubMed Web of Science ®Google Scholar
• Landis GN, Doherty D, Tower J. Analysis of Drosophila melanogaster Lifespan. Methods Mol Biol. 2020;2144:47–56. Epub 2020/05/16. PubMed PMID: 32410023; PMCID: PMC8016145.
   PubMedGoogle Scholar
• R: A language and environment for statistical computing. [Internet]. R Foundation for Statistical Computing, Vienna Austria. 2020. Available from: https://www.r-project.org/
   Google Scholar
• Wu Q, Yu G, Park SJ, et al.Excreta Quantification (EX-Q) for longitudinal measurements of food intake in Drosophila.iScience.2020;23(1):100776. Epub 2020/01/07. Epub 2020/01/07
   PubMed Web of Science ®Google Scholar
• Micchelli CA. Whole-mount immunostaining of the adult Drosophila gastrointestinal tract.Methods.2014;68(1):273–279. Epub 2014/04/01. PubMed PMID: 24680702; PMCID: PMC4430120
   PubMed Web of Science ®Google Scholar
• Simon JA, Lis JT. A germline transformation analysis reveals flexibility in the organization of heat shock consensus elements. Nucleic Acids Res. 1987;15(7):2971–2988. PubMed PMID: 3562243; PMCID: PMC340710.
   PubMed Web of Science ®Google Scholar
• Wheeler JC, Bieschke ET, Tower J. Muscle-specific expression of Drosophila hsp70 in response to aging and oxidative stress. Proc Natl Acad Sci U S A. 1995;92(22):10408–10412. PubMed PMID: 7479794.
   PubMed Web of Science ®Google Scholar
• Ma P, Zhang Y, Liang Q, et al.Mifepristone (RU486) inhibits dietary lipid digestion by antagonizing the role of glucocorticoid receptor on lipase transcription.iScience.2021;24(6):102507. Epub 2021/07/27. PubMed PMID: 34308280; PMCID: PMC8257970
   PubMed Web of Science ®Google Scholar
• Schlaepfer IR, Joshi M. CPT1A-mediated fat oxidation, mechanisms, and therapeutic potential. Endocrinology. 2020;161(2). Epub 2020/01/05. PubMed PMID: 31900483 doi:10.1210/endocr/bqz046
   PubMed Web of Science ®Google Scholar
• Thimgan MS, Suzuki Y, Seugnet L, et al.The perilipin homologue, lipid storage droplet 2, regulates sleep homeostasis and prevents learning impairments following sleep loss.PLoS Biol.2010;8(8):e1000466. Epub 2010/09/09. PubMed PMID: 20824166; PMCID: PMC2930866.
   PubMed Web of Science ®Google Scholar
• Murakami K, Yurgel ME, Stahl BA, et al.Translin is required for metabolic regulation of sleep.Curr Biol.2016;26(7):972–980. Epub 2016/03/30. PubMed PMID: 27020744; PMCID: PMC4846466
   PubMed Web of Science ®Google Scholar
• Singh SR, Zeng X, Zhao J, et al.The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila.Nature.2016;538(7623):109–113. Epub 2016/09/30. PubMed PMID: 27680705; PMCID: PMC7798135
   PubMed Web of Science ®Google Scholar
• Bouagnon AD, Lin L, Srivastava S, et al.Intestinal peroxisomal fatty acid beta-oxidation regulates neural serotonin signaling through a feedback mechanism.PLoS Biol.2019;17(12):e3000242. Epub 2019/12/06. PubMed PMID: 31805041; PMCID: PMC6917301
   PubMed Web of Science ®Google Scholar
• Horn CC, Ji H, Friedman MI. Etomoxir, a fatty acid oxidation inhibitor, increases food intake and reduces hepatic energy status in rats.Physiol Behav.2004;81(1):157–162. Epub 2004/04/03. PubMed PMID: 15059695
   PubMed Web of Science ®Google Scholar
• King-Jones K, Thummel CS. Nuclear receptors–a perspective from Drosophila. Nat Rev Genet. 2005;6(4):311–323. PubMed PMID: 15803199.
   PubMed Web of Science ®Google Scholar
• Jafari M, Khodayari B, Felgner J, et al.Pioglitazone: an anti-diabetic compound with anti-aging properties.Biogerontology.2007;8(6):639–651. Epub 2007/07/14. PubMed PMID: 17628757
   PubMed Web of Science ®Google Scholar
• Simon AF, Shih C, Mack A, et al. Steroid control of longevity in Drosophila melanogaster. Science. 2003;299(5611):1407–1410. PubMed PMID: 12610309.
   PubMed Web of Science ®Google Scholar
• Tricoire H, Battisti V, Trannoy S, et al.The steroid hormone receptor EcR finely modulates Drosophila lifespan during adulthood in a sex-specific manner.Mech Ageing Dev.2009;130(8):547–552. Epub 2009/06/03. PubMed PMID: 19486910
   PubMed Web of Science ®Google Scholar
• Morris LX, Spradling AC, Bökel C. Steroid signaling within Drosophila ovarian epithelial cells sex-specifically modulates early germ cell development and meiotic entry.PLoS One.2012;7(10):e46109. Epub 2012/10/12. PubMed PMID: 23056242; PMCID: PMC3462805
   PubMed Web of Science ®Google Scholar
• Robinson PD, Morgan ED, Wilson ID, et al. The metabolism of ingested and injected [3 H]ecdysone by final instar larvae of Heliothis armigera. Physiol Entomol. 1987;12(3):321–330.
   Web of Science ®Google Scholar
• Wing KD, Slawecki RA, Carlson GR. RH 5849, a Nonsteroidal ecdysone agonist: effects on larval lepidoptera.Science.1988;241(4864):470–472. Epub 1988/07/22. PubMed PMID: 17792610
   PubMed Web of Science ®Google Scholar
• Schnebel EM, Grossfield J. Mating-temperature range in Drosophila.Evolution.1984;38(6):1296–1307. Epub 1984/11/01. Epub 1984/11/01
   PubMed Web of Science ®Google Scholar
• Miwa Y, Koganezawa M, Yamamoto D. Antennae sense heat stress to inhibit mating and promote escaping in Drosophila females.J Neurogenet.2018;32(4):353–363. Epub 2018/09/21. PubMed PMID: 30231794
   PubMed Web of Science ®Google Scholar
• Struhl G, Basler K. Organizing activity of wingless protein in Drosophila. Cell. 1993;72(4):527–540. PubMed PMID: 8440019.
   PubMed Web of Science ®Google Scholar
• Beebe K, Robins MM, Hernandez EJ, et al.Drosophila estrogen-related receptor directs a transcriptional switch that supports adult glycolysis and lipogenesis.Genes Dev.2020;34(9–10):701–714. Epub 2020/03/14. PubMed PMID: 32165409; PMCID: PMC7197351
   PubMed Web of Science ®Google Scholar