Biogerontology

, Volume 18, Issue 2, pp 263–273 | Cite as

Jujube (Ziziphus Jujuba Mill.) fruit feeding extends lifespan and increases tolerance to environmental stresses by regulating aging-associated gene expression in Drosophila

Research Article

Abstract

Jujube (Ziziphus Jujuba Mill.) fruit has been utilized as an adjunct to alleviate medical symptoms including, but not limited to, anorexia, fatigue, anxiety and mild diarrhea for centuries. Despite a growing body of literature revealing jujube fruit’s health promoting properties such as anti-cancer, anti-inflammation and anti-oxidant effects (shown with cell-based in vitro platforms), there is a paucity of studies systemically examining its impact on whole organisms or throughout the entire course of life utilizing in vivo model systems. Thus, here in this study, we conducted a series of experiments to investigate if jujube fruit can modify an organism’s longevity using a live Drosophila model. We found that jujube fruit feeding extended not only lifespan but also healthspan examined by stress assays such as starvation and paraquat treatment. In an effort to shed light on the mechanisms of these jujube-related benefits at the molecular level, we report that messenger RNA (mRNA) levels of 14-3-3ε, a negative FoxO (Forkhead box O transcription factor) regulator, was dramatically diminished while the abundance of d4E-BP mRNA transcript (drosophila eukaryotic translation initiation factor 4E binding protein), a FoxO target gene, was increased, suggesting enhanced FoxO activity with jujube fruit feeding. In conclusion, we hope our results will lead to multidisciplinary research to investigate the potential benefit of jujube fruit as a novel anti-aging agent.

Keywords

Jujube fruit dFoxO d4E-BP Drosophila Longevity 

Supplementary material

10522_2017_9686_MOESM1_ESM.docx (117 kb)
Supplementary material 1 (DOCX 116 kb)

References

  1. Atanasov AG et al (2015) Discovery and resupply of pharmacologically active plant-derived natural products: a review. Biotechnol Adv 33:1582–1614. doi:10.1016/j.biotechadv.2015.08.001 CrossRefPubMedPubMedCentralGoogle Scholar
  2. Bross TG, Rogina B, Helfand SL (2005) Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction. Aging Cell 4:309–317. doi:10.1111/j.1474-9726.2005.00181.x CrossRefPubMedGoogle Scholar
  3. Brown JE (2014) Can restricting calories help you to live longer? Post Reprod Health 20:16–18. doi:10.1177/1754045314521553 CrossRefPubMedGoogle Scholar
  4. Fontana L, Partridge L (2015) Promoting health and longevity through diet: from model organisms to humans. Cell 161:106–118. doi:10.1016/j.cell.2015.02.020 CrossRefPubMedPubMedCentralGoogle Scholar
  5. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span–from yeast to humans. Science 328:321–326. doi:10.1126/science.1172539 CrossRefPubMedPubMedCentralGoogle Scholar
  6. Gao QH, Wu CS, Wang M (2013) The jujube (Ziziphus jujuba Mill.) fruit: a review of current knowledge of fruit composition and health benefits. J Agric Food Chem 61:3351–3363. doi:10.1021/jf4007032 CrossRefPubMedGoogle Scholar
  7. Ghimire S, Kim MS (2015a) Defensive behavior against noxious heat stimuli is declined with aging due to decreased pain-associated gene expression in Drosophila. Biomol Ther (Seoul) 23:290–295. doi:10.4062/biomolther.2014.147 CrossRefGoogle Scholar
  8. Ghimire S, Kim MS (2015b) Enhanced locomotor activity is required to exert dietary restriction-dependent increase of stress resistance in Drosophila. Oxid Med Cell Longev 2015:813801. doi:10.1155/2015/813801 CrossRefPubMedPubMedCentralGoogle Scholar
  9. Goyal R, Sharma PL, Singh M (2011) Possible attenuation of nitric oxide expression in anti-inflammatory effect of Ziziphus jujuba in rat J. Nat Med 65:514–518. doi:10.1007/s11418-011-0531-0 CrossRefGoogle Scholar
  10. Haghighat A, Mader S, Pause A, Sonenberg N (1995) Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J 14:5701–5709PubMedPubMedCentralGoogle Scholar
  11. Huang YL, Yen GC, Sheu F, Chau CF (2008) Effects of water-soluble carbohydrate concentrate from Chinese jujube on different intestinal and fecal indices. J Agric Food Chem 56:1734–1739. doi:10.1021/jf072664z CrossRefPubMedGoogle Scholar
  12. Jaiswal Y, Liang Z, Zhao Z (2016) Botanical drugs in ayurveda and traditional chinese medicine. J Ethnopharmacol. doi:10.1016/j.jep.2016.06.052 PubMedGoogle Scholar
  13. Junger MA et al (2003) The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J Biol 2:20. doi:10.1186/1475-4924-2-20 CrossRefPubMedPubMedCentralGoogle Scholar
  14. Kapahi P, Zid BM, Harper T, Koslover D, Sapin V, Benzer S (2004) Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14:885–890. doi:10.1016/j.cub.2004.03.059 CrossRefPubMedPubMedCentralGoogle Scholar
  15. Kapahi P, Chen D, Rogers AN, Katewa SD, Li PW, Thomas EL, Kockel L (2010) With TOR, less is more: a key role for the conserved nutrient-sensing TOR pathway in aging. Cell Metab 11:453–465. doi:10.1016/j.cmet.2010.05.001 CrossRefPubMedPubMedCentralGoogle Scholar
  16. Katewa SD et al (2012) Intramyocellular fatty-acid metabolism plays a critical role in mediating responses to dietary restriction in Drosophila melanogaster. Cell Metab 16:97–103. doi:10.1016/j.cmet.2012.06.005 CrossRefPubMedPubMedCentralGoogle Scholar
  17. Kenyon C (2001) A conserved regulatory system for aging. Cell 105:165–168CrossRefPubMedGoogle Scholar
  18. Kim MS (2013) Korean red ginseng tonic extends lifespan in D. melanogaster. Biomol Ther (Seoul) 21:241–245. doi:10.4062/biomolther.2013.024 CrossRefGoogle Scholar
  19. Kong LY, Tan RX (2015) Artemisinin, a miracle of traditional Chinese medicine. Nat Prod Rep 32:1617–1621. doi:10.1039/c5np00133a CrossRefPubMedGoogle Scholar
  20. Kubota H, Morii R, Kojima-Yuasa A, Huang X, Yano Y, Matsui-Yuasa I (2009) Effect of Zizyphus jujuba extract on the inhibition of adipogenesis in 3T3-L1 preadipocytes. Am J Chin Med 37:597–608. doi:10.1142/S0192415X09007089 CrossRefPubMedGoogle Scholar
  21. Li N, Zhou L, Li W, Liu Y, Wang J, He P (2015) Protective effects of ginsenosides Rg1 and Rb1 on an Alzheimer’s disease mouse model: a metabolomics study. J Chromatogr B 985:54–61. doi:10.1016/j.jchromb.2015.01.016 CrossRefGoogle Scholar
  22. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25:402–408. doi:10.1006/meth.2001.1262 CrossRefPubMedGoogle Scholar
  23. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194–1217. doi:10.1016/j.cell.2013.05.039 CrossRefPubMedPubMedCentralGoogle Scholar
  24. Mader S, Sonenberg N (1995) Cap binding complexes and cellular growth control. Biochimie 77:40–44CrossRefPubMedGoogle Scholar
  25. Mercken EM, Carboneau BA, Krzysik-Walker SM, de Cabo R (2012) Of mice and men: the benefits of caloric restriction, exercise, and mimetics. Ageing Res Rev 11:390–398. doi:10.1016/j.arr.2011.11.005 CrossRefPubMedGoogle Scholar
  26. Moghadamtousi SZ, Kadir HA, Hassandarvish P, Tajik H, Abubakar S, Zandi K (2014) A review on antibacterial, antiviral, and antifungal activity of curcumin. Biomed Res Int 2014:186864. doi:10.1155/2014/18686 PubMedGoogle Scholar
  27. Niccoli T, Partridge L (2012) Ageing as a risk factor for disease. Curr Biol 22:R741–R752. doi:10.1016/j.cub.2012.07.024 CrossRefPubMedGoogle Scholar
  28. Nielsen MD, Luo X, Biteau B, Syverson K, Jasper H (2008) 14-3-3 Epsilon antagonizes FoxO to control growth, apoptosis and longevity in Drosophila. Aging Cell 7:688–699. doi:10.1111/j.1474-9726.2008.00420.x CrossRefPubMedGoogle Scholar
  29. Outlaw WH, Zhang SQ, Riddle KA, Womble AK, Anderson LC, Outlaw WM, Outlaw NN, Outlaw EC, Thistle AB (2002) The Jujube (Ziziphus jujuba Mill.), a multipurpose plant. Econ Bot 56:198–200CrossRefGoogle Scholar
  30. Partridge L, Piper MD, Mair W (2005) Dietary restriction in Drosophila. Mech Ageing Dev 126:938–950. doi:10.1016/j.mad.2005.03.023 CrossRefPubMedGoogle Scholar
  31. Plastina P et al (2012) Identification of bioactive constituents of Ziziphus jujube fruit extracts exerting antiproliferative and apoptotic effects in human breast cancer cells. J Ethnopharmacol 140:325–332. doi:10.1016/j.jep.2012.01.022 CrossRefPubMedGoogle Scholar
  32. Rana SV, Pal R, Vaiphei K, Sharma SK, Ola RP (2011) Garlic in health and disease. Nutr Res Rev 24:60–71. doi:10.1017/S0954422410000338 CrossRefPubMedGoogle Scholar
  33. Ren CWJ (2000) Rise and fall of Qin dynasty. Asiapac Books PTE LtdGoogle Scholar
  34. Rush B, Sandver S, Bruer J, Roche R, Wells M, Giebultowicz J (2007) Mating increases starvation resistance and decreases oxidative stress resistance in Drosophila melanogaster females. Aging Cell 6:723–726. doi:10.1111/j.1474-9726.2007.00322.x CrossRefPubMedGoogle Scholar
  35. Salih DA, Brunet A (2008) FoxO transcription factors in the maintenance of cellular homeostasis during aging. Curr Opin Cell Biol 20:126–136. doi:10.1016/j.ceb.2008.02.005 CrossRefPubMedPubMedCentralGoogle Scholar
  36. Song BK, Won JH, Kim S (2016) Historical medical value of Donguibogam. J Pharmacopunct 19:16–20. doi:10.3831/KPI.2016.19.002 CrossRefGoogle Scholar
  37. Suckow BK, Suckow MA (2006) Lifespan extension by the antioxidant curcumin in Drosophila melanogaster Int. J Biomed Sci 2:402–405Google Scholar
  38. Tettweiler G, Miron M, Jenkins M, Sonenberg N, Lasko PF (2005) Starvation and oxidative stress resistance in Drosophila are mediated through the eIF4E-binding protein, d4E-BP. Genes Dev 19:1840–1843. doi:10.1101/gad.1311805 CrossRefPubMedPubMedCentralGoogle Scholar
  39. Vahedi F, Fathi Najafi M, Bozari K (2008) Evaluation of inhibitory effect and apoptosis induction of Zyzyphus Jujube on tumor cell lines, an in vitro preliminary study. Cytotechnology 56:105–111. doi:10.1007/s10616-008-9131-6 CrossRefPubMedPubMedCentralGoogle Scholar
  40. Wang BW, Ramey DR, Schettler JD, Hubert HB, Fries JF (2002) Postponed development of disability in elderly runners: a 13-year longitudinal study. Arch Intern Med 162:2285–2294CrossRefPubMedGoogle Scholar
  41. Webb AE, Brunet A (2014) FOXO transcription factors: key regulators of cellular quality control. Trends Biochem Sci 39:159–169. doi:10.1016/j.tibs.2014.02.003 CrossRefPubMedPubMedCentralGoogle Scholar
  42. Wu J, Jeong HK, Bulin SE, Kwon SW, Park JH, Bezprozvanny I (2009) Ginsenosides protect striatal neurons in a cellular model of Huntington’s disease. J Neurosci Res 87:1904–1912. doi:10.1002/jnr.22017 CrossRefPubMedPubMedCentralGoogle Scholar
  43. Xing X, Liu F, Xiao J, So KF (2016) Neuro-protective mechanisms of Lycium barbarum. Neuromol Med 18:253–263. doi:10.1007/s12017-016-8393-y CrossRefGoogle Scholar
  44. Yu L, Jiang BP, Luo D, Shen XC, Guo S, Duan JA, Tang YP (2012) Bioactive components in the fruits of Ziziphus jujuba Mill. against the inflammatory irritant action of Euphorbia plants. Phytomedicine 19:239–244. doi:10.1016/j.phymed.2011.09.071 CrossRefPubMedGoogle Scholar
  45. Zhou T et al (2016) Neuroprotective effects of ginsenoside Rg1 through the Wnt/beta-catenin signaling pathway in both in vivo and in vitro models of Parkinson’s disease. Neuropharmacology 101:480–489. doi:10.1016/j.neuropharm.2015.10.024 CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2017

Authors and Affiliations

  1. 1.College of PharmacyInje UniversityGimhaeRepublic of Korea

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