Advertisement

Circadian clock genes’ overexpression in Drosophila alters diet impact on lifespan

  • Ilya Solovev
  • Eugenia Shegoleva
  • Alexander Fedintsev
  • Mikhail Shaposhnikov
  • Alexey Moskalev
Research Article

Abstract

Diet restriction is one of the most accurately confirmed interventions which extend lifespan. Genes coding circadian core clock elements are known to be the key controllers of cell metabolism especially in aging aspect. The molecular mechanisms standing behind the phenomenon of diet-restriction-mediated life extension are connected to circadian clock either. Here we investigate the effects of protein-rich and low-protein diets on lifespan observed in fruit flies overexpressing core clock genes (cry, per, Clk, cyc and tim). The majority of core clock genes being upregulated in peripheral tissues (muscles and fat body) on protein-rich diet significantly decrease the lifespan of male fruit flies from 5 to 61%. Nevertheless, positive increments of median lifespan were observed in both sexes, males overexpressing cry in fat body lived 20% longer on poor diet. Overexpression of per also on poor medium resulted in life extension in female fruit flies. Diet restriction reduces mortality caused by overexpression of core clock genes. Cox-regression model revealed that diet restriction seriously decreases mortality risks of flies which overexpress core clock genes. The hazard ratios are lower for flies overexpressing clock genes in fat body relatively to muscle-specific overexpression. The present work suggests a phenomenological view of how two peripheral circadian oscillators modify effects of rich and poor diets on lifespan and hazard ratios.

Keywords

Circadian clock Aging Lifespan Diet restriction Feeding assay Drosophila melanogaster 

Notes

Acknowledgements

We are grateful to Dr. Patrick Emery (University of Massachusetts Medical School, USA), Dr. Paul Hardin (Texas A&M University, USA), Dr. Keshishian (Yale University, USA), Dr. Laurent Seroude (Queen’s University, Canada) and the Bloomington stock center (Indiana University, USA) for providing the Drosophila strains.

Funding

The study was carried out within the framework of the state task on themes “Molecular-genetic mechanisms of aging, lifespan, and stress resistance of Drosophila melanogaster”, state registration No. AAAA-A18-118011120004-5 and “A combination of factors of different nature (low temperature, lack of lighting, restrictive diet, and geroprotector) to maximize the lifespan of Drosophila. Complex UrB RAS Programme” No. 18-7-4-23, state registration No. AAAA-A18-118011120008-3.

Compliance with ethical standards

Conflict of interest

The authors have no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Supplementary material

10522_2018_9784_MOESM1_ESM.pdf (683 kb)
Supplementary material 1 (PDF 683 kb)

References

  1. Armstrong AR, Laws KM, Drummond-Barbosa D (2014) Adipocyte amino acid sensing controls adult germline stem cell number via the amino acid response pathway and independently of Target of Rapamycin signaling in Drosophila. Development 141:4479–4488CrossRefGoogle Scholar
  2. Arthaut LD, Jourdan N, Mteyrek A, Procopio M, El-Esawi M, d’Harlingue A, Bouchet PE, Witczak J, Ritz T, Klarsfeld A, Birman S, Usselman RJ, Hoecker U, Martino CF, Ahmad M (2017) Blue-light induced accumulation of reactive oxygen species is a consequence of the Drosophila cryptochrome photocycle. PLoS ONE 12:e0171836CrossRefGoogle Scholar
  3. Breslow N (1970) A generalized Kruskal–Wallis test for comparing K samples subject to unequal patterns of censorship. Biometrika 57(3):579–594CrossRefGoogle Scholar
  4. Chaves I, van der Horst GT, Schellevis R, Nijman RM, Koerkamp MG, Holstege FC, Smidt MP, Hoekman MF (2014) Insulin-FOXO3 signaling modulates circadian rhythms via regulation of clock transcription. Curr Biol 24:1248–1255CrossRefGoogle Scholar
  5. Doi M, Hirayama J, Sassone-Corsi P (2006) Circadian regulator CLOCK is a histone acetyltransferase. Cell 125:497-508CrossRefGoogle Scholar
  6. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span—from yeast to humans. Science 328:321–326CrossRefGoogle Scholar
  7. Goda T, Mirowska K, Currie J, Kim M-H, Rao NV, Bonilla G, Wijnen H (2011) Adult circadian behavior in Drosophila requires developmental expression of cycle, but not period. PLoS Genet 7:e1002167CrossRefGoogle Scholar
  8. Graveley BR, Brooks AN, Carlson JW, Duff MO, Landolin JM, Yang L, Artieri CG, van Baren MJ, Boley N, Booth BW, Brown JB, Cherbas L, Davis CA, Dobin A, Li R, Lin W, Malone JH, Mattiuzzo NR, Miller D, Sturgill D, Tuch BB, Zaleski C, Zhang D, Blanchette M, Dudoit S, Eads B, Green RE, Hammonds A, Jiang L, Kapranov P, Langton L, Perrimon N, Sandler JE, Wan KH, Willingham A, Zhang Y, Zou Y, Andrews J, Bickel PJ, Brenner SE, Brent MR, Cherbas P, Gingeras TR, Hoskins RA, Kaufman TC, Oliver B, Celniker SE (2011) The developmental transcriptome of Drosophila melanogaster. Nature 471:473–479CrossRefGoogle Scholar
  9. Hardin PE, Yu W (2006) Circadian transcription: passing the HAT to CLOCK. Cell 125:424–426CrossRefGoogle Scholar
  10. Hirayama J, Sahar S, Grimaldi B, Tamaru T, Takamatsu K, Nakahata Y, Sassone-Corsi P (2007) CLOCK-mediated acetylation of BMAL1 controls circadian function. Nature 450:1086–1090CrossRefGoogle Scholar
  11. Holloszy JO, Schechtman KB (1991) Interaction between exercise and food restriction: effects on longevity of male rats. J Appl Physiol 70:1529–1535CrossRefGoogle Scholar
  12. Kapahi P, Kaeberlein M, Hansen M (2017) Dietary restriction and lifespan: lessons from invertebrate models. Ageing Res Rev 39:3–14CrossRefGoogle Scholar
  13. Katewa SD, Kapahi P (2011) Role of TOR signaling in aging and related biological processes in Drosophila melanogaster. Exp Gerontol 46:382–390CrossRefGoogle Scholar
  14. Katewa SD, Demontis F, Kolipinski M, Hubbard A, Gill MS, Perrimon N, Melov S, Kapahi P (2012) Intramyocellular fatty-acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster. Cell Metab 16:97–103CrossRefGoogle Scholar
  15. Katewa SD, Akagi K, Bose N, Rakshit K, Camarella T, Zheng X, Hall D, Davis S, Nelson CS, Brem RB (2016) Peripheral circadian clocks mediate dietary restriction-dependent changes in lifespan and fat metabolism in Drosophila. Cell Metab 23:143–154CrossRefGoogle Scholar
  16. Khapre RV, Kondratova AA, Patel S, Dubrovsky Y, Wrobel M, Antoch MP, Kondratov RV (2014) BMAL1-dependent regulation of the mTOR signaling pathway delays aging. Aging (Albany NY) 6:48CrossRefGoogle Scholar
  17. Kumar S, Chen D, Sehgal A (2012) Dopamine acts through Cryptochrome to promote acute arousal in Drosophila. Genes Dev 26:1224–1234CrossRefGoogle Scholar
  18. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT Method. Methods 25:402–408CrossRefGoogle Scholar
  19. Moskalev A, Vaiserman AM (2017) Epigenetics of aging and longevity. Elsevier Science, AmsterdamGoogle Scholar
  20. Moskalev A, Anisimov V, Aliper A, Artemov A, Asadullah K, Belsky D, Baranova A, de Grey A, Dixit VD, Debonneuil E, Dobrovolskaya E, Fedichev P, Fedintsev A, Fraifeld V, Franceschi C, Freer R, Fulop T, Feige J, Gems D, Gladyshev V, Gorbunova V, Irincheeva I, Jager S, Jazwinski SM, Kaeberlein M, Kennedy B, Khaltourina D, Kovalchuk I, Kovalchuk O, Kozin S, Kulminski A, Lashmanova E, Lezhnina K, Liu GH, Longo V, Mamoshina P, Maslov A, Pedro de Magalhaes J, Mitchell J, Mitnitski A, Nikolsky Y, Ozerov I, Pasyukova E, Peregudova D, Popov V, Proshkina E, Putin E, Rogaev E, Rogina B, Schastnaya J, Seluanov A, Shaposhnikov M, Simm A, Skulachev V, Skulachev M, Solovev I, Spindler S, Stefanova N, Suh Y, Swick A, Tower J, Gudkov AV, Vijg J, Voronkov A, West M, Wagner W, Yashin A, Zemskaya N, Zhumadilov Z, Zhavoronkov A (2017) A review of the biomedical innovations for healthy longevity. Aging (Albany NY) 9:7–25CrossRefGoogle Scholar
  21. Nakahata Y, Grimaldi B, Sahar S, Hirayama J, Sassone-Corsi P (2007) Signaling to the circadian clock: plasticity by chromatin remodeling. Curr Opin Cell Biol 19:230–237CrossRefGoogle Scholar
  22. Oishi K, Shiota M, Sakamoto K, Kasamatsu M, Ishida N (2004) Feeding is not a more potent Zeitgeber than the light-dark cycle in Drosophila. NeuroReport 15:739–743CrossRefGoogle Scholar
  23. Osterwalder T, Yoon KS, White BH, Keshishian H (2001) A conditional tissue-specific transgene expression system using inducible GAL4. Proc Natl Acad Sci USA 98:12596–12601CrossRefGoogle Scholar
  24. Peschel N, Helfrich-Förster C (2011) Setting the clock—by nature: circadian rhythm in the fruitfly Drosophila melanogaster. FEBS Lett 585:1435–1442CrossRefGoogle Scholar
  25. Poirier L, Shane A, Zheng J, Seroude L (2008) Characterization of the Drosophila gene-switch system in aging studies: a cautionary tale. Aging Cell 7:758–770CrossRefGoogle Scholar
  26. Prentice RL (1992) Introduction to Cox (1972) regression models and life-tables. In: Kotz S, Johnson NL (eds) Breakthroughs in statistics: methodology and distribution. Springer, New York, pp 519–526CrossRefGoogle Scholar
  27. R Core Team (2013) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna. http://www.R-project.org/
  28. Rakshit K, Krishnan N, Guzik EM, Pyza E, Giebultowicz JM (2012) Effects of aging on the molecular circadian oscillations in Drosophila. Chronobiol Int 29:5–14CrossRefGoogle Scholar
  29. Roman G, Endo K, Zong L, Davis RL (2001) P{Switch}, a system for spatial and temporal control of gene expression in Drosophila melanogaster. Proc Natl Acad Sci USA 98:12602–12607CrossRefGoogle Scholar
  30. Russell RC, Yuan HX, Guan KL (2014) Autophagy regulation by nutrient signaling. Cell Res 24:42–57CrossRefGoogle Scholar
  31. Santos J, Leitão-Correia F, Sousa MJ, Leão C (2016) Dietary restriction and nutrient balance in aging. Oxid Med Cell Longev 2016:4010357PubMedGoogle Scholar
  32. Skorupa DA, Dervisefendic A, Zwiener J, Pletcher SD (2008) Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 7:478–490CrossRefGoogle Scholar
  33. Solovev I, Shaposhnikov M, Kudryavtseva A, Moskalev A (2018) Drosophila melanogaster as a model for studying the epigenetic basis of aging. In: Moskalev A, Vaiserman AM (eds) Epigenetics of aging and longevity. Elsevier, Amsterdam, pp 293–307CrossRefGoogle Scholar
  34. Solovyov I, Dobrovol’skaya E, Moskalev A (2016) Genetic control of circadian rhythms and aging. Russ J Genet 52:343–361CrossRefGoogle Scholar
  35. Ulgherait M, Chen A, Oliva M, Kim H, Canman J, Ja W, Shirasu-Hiza M (2016) Dietary restriction extends the lifespan of circadian mutants tim and per. Cell Metab 24:763–764CrossRefGoogle Scholar
  36. Wang C, Li Q, Redden DT, Weindruch R, Allison DB (2004) Statistical methods for testing effects on “maximum lifespan”. Mech Ageing Dev 125:629–632CrossRefGoogle Scholar
  37. Yang Z, Sehgal A (2001) Role of molecular oscillations in generating behavioral rhythms in Drosophila. Neuron 29:453–467CrossRefGoogle Scholar
  38. Zhao J, Kilman VL, Keegan KP, Peng Y, Emery P, Rosbash M, Allada R (2003) Drosophila clock can generate ectopic circadian clocks. Cell 113:755–766CrossRefGoogle Scholar
  39. Zid BM, Rogers AN, Katewa SD, Vargas MA, Kolipinski MC, Lu TA, Benzer S, Kapahi P (2009) 4E-BP extends lifespan upon dietary restriction by enhancing mitochondrial activity in Drosophila. Cell 139:149–160CrossRefGoogle Scholar

Copyright information

© Springer Nature B.V. 2018

Authors and Affiliations

  1. 1.Laboratory of Molecular Radiobiology and Gerontology, Komi Science Center, Institute of Biology, Ural BranchRussian Academy of SciencesSyktyvkarRussian Federation
  2. 2.Pitirim Sorokin Syktyvkar State UniversitySyktyvkarRussian Federation
  3. 3.Moscow Institute of Physics and TechnologyDolgoprudnyRussian Federation
  4. 4.Laboratory of Post-Genomic Research, Engelhardt Institute of Molecular BiologyRussian Academy of SciencesMoscowRussian Federation

Personalised recommendations