Skip to main content

Advertisement

SpringerLink
Log in

Korean mistletoe (Viscum album coloratum) extract extends the lifespan of nematodes and fruit flies

  • Research Article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Viscum album coloratum (Korean mistletoe) is a semi-parasitic plant that grows on various trees and has a variety of biological functions such as immunomodulation, apoptosis, and anti-tumor activity. In this study, we investigated the effects of Korean mistletoe extract (KME) on lifespan in experimental models using Caenorhabditis elegans and Drosophila melanogaster. Supplementation of KME at 50 μg/ml extended the mean survival time by 9.61 and 19.86 % in worms and flies, respectively. The longevity benefit of KME was not due to reduced feeding, reproduction, and/or locomotion in flies and worms. The supplementation of KME also did not increase resistance to various stresses including heat shock, oxidative, or starvation stresses. Furthermore, KME did not further extend the lifespan of flies fed a dietary restricted diet but did increase the expression of Sir2, one of the target genes of dietary restriction, suggesting that KME may function as a putative dietary restriction mimetic. These results also suggest that the longevity promoting effects of KME may be an example of mild stress-induced hormesis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  • Agarwal B, Baur JA (2011) Resveratrol and life extension. Ann N Y Acad Sci 1215:138–143

    Article  CAS  PubMed  Google Scholar 

  • Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444(7117):337–342

    Article  CAS  PubMed  Google Scholar 

  • Biteau B, Hochmuth CE, Jasper H (2008) JNK activity in somatic stem cells causes loss of tissue homeostasis in the aging Drosophila gut. Cell Stem Cell 3(4):442–455

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Bjedov I, Toivonen JM, Kerr F, Slack C, Jacobson J, Foley A, Partridge L (2010) Mechanisms of life span extension by rapamycin in the fruit fly Drosophila melanogaster. Cell Metab 11(1):35–46

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Blagosklonny MV (2010) Calorie restriction: decelerating mTOR-driven aging from cells to organisms (including humans). Cell Cycle 9(4):683–688

    Article  CAS  PubMed  Google Scholar 

  • Blattler SM, Cunningham JT, Verdeguer F, Chim H, Haas W, Liu H, Romanino K, Ruegg MA, Gygi SP, Shi Y, Puigserver P (2012) Yin Yang 1 deficiency in skeletal muscle protects against rapamycin-induced diabetic-like symptoms through activation of insulin/IGF signaling. Cell Metab 15(4):505–517

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Cabreiro F, Au C, Leung KY, Vergara-Irigaray N, Cocheme HM, Noori T, Weinkove D, Schuster E, Greene ND, Gems D (2013) Metformin retards aging in C. elegans by altering microbial folate and methionine metabolism. Cell 153(1):228–239

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Chandrashekara KT, Shakarad MN (2011) Aloe vera or resveratrol supplementation in larval diet delays adult aging in the fruit fly, Drosophila melanogaster. J Gerontol A Biol Sci Med Sci 66(9):965–971

    Article  PubMed  Google Scholar 

  • Choi JH, Lyu SY, Lee HJ, Jung J, Park WB, Kim GJ (2012) Korean mistletoe lectin regulates self-renewal of placenta-derived mesenchymal stem cells via autophagic mechanisms. Cell Prolif 45(5):420–429

    Article  CAS  PubMed  Google Scholar 

  • Elsasser-Beile U, Voss M, Schuhle R, Wetterauer U (2000) Biological effects of natural and recombinant mistletoe lectin and an aqueous mistletoe extract on human monocytes and lymphocytes in vitro. J Clin Lab Anal 14(6):255–259

    Article  CAS  PubMed  Google Scholar 

  • Flatt T (2011) Survival costs of reproduction in Drosophila. Exp Gerontol 46(5):369–375

    Article  PubMed  Google Scholar 

  • Fontana L, Partridge L, Longo VD (2010) Extending healthy life span—from yeast to humans. Science 328(5976):321–326

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Frank U, Engels I, Wagner A, Lacour M, Daschner FD (2003) Influence of mistletoe (Viscum album) extracts on phagocytosis/burst activity of human phagocytes. Eur J Clin Microbiol Infect Dis 22(8):501–503

    Article  CAS  PubMed  Google Scholar 

  • Guha S, Cao M, Kane RM, Savino AM, Zou S, Dong Y (2013) The longevity effect of cranberry extract in Caenorhabditis elegans is modulated by daf-16 and osr-1. Age (Dordr) 35(5):1559–1574

    Article  Google Scholar 

  • Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460(7253):392–395

    CAS  PubMed Central  PubMed  Google Scholar 

  • Hostanska K, Hajto T, Spagnoli GC, Fischer J, Lentzen H, Herrmann R (1995) A plant lectin derived from Viscum album induces cytokine gene expression and protein production in cultures of human peripheral blood mononuclear cells. Nat Immun 14(5–6):295–304

    CAS  PubMed  Google Scholar 

  • Howitz KT, Bitterman KJ, Cohen HY, Lamming DW, Lavu S, Wood JG, Zipkin RE, Chung P, Kisielewski A, Zhang LL, Scherer B, Sinclair DA (2003) Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan. Nature 425(6954):191–196

    Article  CAS  PubMed  Google Scholar 

  • Jafari M, Rose MR (2006) Rules for the use of model organisms in anti-aging pharmacology. Aging Cell 5(1):17–22

    Article  CAS  PubMed  Google Scholar 

  • Jafari M, Felgner JS, Bussel II, Hutchili T, Khodayari B, Rose MR, Vince-Cruz C, Mueller LD (2007) Rhodiola: a promising anti-aging Chinese herb. Rejuvenation Res 10(4):587–602

    Article  PubMed  Google Scholar 

  • Jung MJ, Yoo YC, Lee KB, Kim JB, Song KS (2004) Isolation of epi-oleanolic acid from Korean mistletoe and its apoptosis-inducing activity in tumor cells. Arch Pharm Res 27(8):840–844

    Article  CAS  PubMed  Google Scholar 

  • Jung HY, Lee AN, Kim SJ, Park SM, Song TJ, Ko BW, Kim YH, An HS, Yoo YC, Min BR, Kim JB (2008) Effect of Korean mistletoe (Viscum album coloratum) Extract (KME) on the extensions of life span in silkworm moth. Bombyx Mori. Kor J Parmacogn 39(4):310–315

    Google Scholar 

  • Jung HY, Lee AN, Song TJ, An HS, Kim YH, Kim KD, Kim IB, Kim KS, Han BS, Kim CH, Kim KS, Kim JB (2012) Korean mistletoe (Viscum album coloratum) extract improves endurance capacity in mice by stimulating mitochondrial activity. J Med Food 15(7):621–628

    Article  PubMed  Google Scholar 

  • Khil LY, Kim W, Lyu S, Park WB, Yoon JW, Jun HS (2007) Mechanisms involved in Korean mistletoe lectin-induced apoptosis of cancer cells. World J Gastroenterol 13(20):2811–2818

    CAS  PubMed  Google Scholar 

  • Khwaja TA, Dias CB, Pentecost S (1986) Recent studies on the anticancer activities of mistletoe (Viscum album) and its alkaloids. Oncology 43(Suppl 1):42–50

    Article  CAS  PubMed  Google Scholar 

  • Kim BK, Choi MJ, Park KY, Cho EJ (2010) Protective effects of Korean mistletoe lectin on radical-induced oxidative stress. Biol Pharm Bull 33(7):1152–1158

    Article  CAS  PubMed  Google Scholar 

  • Lam YY, Peterson CM, Ravussin E (2013) Resveratrol vs. calorie restriction: data from rodents to humans. Exp Gerontol 48(10):1018–1024

    Article  CAS  PubMed  Google Scholar 

  • Lee SH, Min KJ (2013) Caloric restriction and its mimetics. BMB Rep 46(4):181–187

    Article  CAS  PubMed  Google Scholar 

  • Lee KS, Lee BS, Semnani S, Avanesian A, Um CY, Jeon HJ, Seong KM, Yu K, Min KJ, Jafari M (2010a) Curcumin extends life span, improves health span, and modulates the expression of age-associated aging genes in Drosophila melanogaster. Rejuvenation Res 13(5):561–570

    Article  CAS  PubMed  Google Scholar 

  • Lee SJ, Hwang AB, Kenyon C (2010b) Inhibition of respiration extends C. elegans life span via reactive oxygen species that increase HIF-1 activity. Curr Biol 20(23):2131–2136

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Liao VH, Yu CW, Chu YJ, Li WH, Hsieh YC, Wang TT (2011) Curcumin-mediated lifespan extension in Caenorhabditis elegans. Mech Ageing Dev 132(10):480–487

    Article  CAS  PubMed  Google Scholar 

  • Lin SJ, Defossez PA, Guarente L (2000) Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289(5487):2126–2128

    Article  CAS  PubMed  Google Scholar 

  • Mansky PJ (2002) Mistletoe and cancer: controversies and perspectives. Semin Oncol 29(6):589–594

    Article  PubMed  Google Scholar 

  • Marchal J, Pifferi F, Aujard F (2013) Resveratrol in mammals: effects on aging biomarkers, age-related diseases, and life span. Ann N Y Acad Sci 1290:67–73

    Article  CAS  PubMed  Google Scholar 

  • Onay-Ucar E, Karagoz A, Arda N (2006) Antioxidant activity of Viscum album ssp. album. Fitoterapia 77(7–8):556–560

    Article  PubMed  Google Scholar 

  • Onken B, Driscoll M (2010) Metformin induces a dietary restriction-like state and the oxidative stress response to extend C. elegans Healthspan via AMPK, LKB1, and SKN-1. PLoS ONE 5(1):e8758

    Article  PubMed Central  PubMed  Google Scholar 

  • Orhan DD, Aslan M, Sendogdu N, Ergun F, Yesilada E (2005) Evaluation of the hypoglycemic effect and antioxidant activity of three Viscum album subspecies (European mistletoe) in streptozotocin-diabetic rats. J Ethnopharmacol 98(1–2):95–102

    Article  PubMed  Google Scholar 

  • Park JH, Hyun CK, Shin HK (1999) Cytotoxic effects of the components in heat-treated mistletoe (Viscum album). Cancer Lett 139(2):207–213

    Article  CAS  PubMed  Google Scholar 

  • Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8(2):157–168

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Peng C, Zuo Y, Kwan KM, Liang Y, Ma KY, Chan HY, Huang Y, Yu H, Chen ZY (2012) Blueberry extract prolongs lifespan of Drosophila melanogaster. Exp Gerontol 47(2):170–178

    Article  CAS  PubMed  Google Scholar 

  • Piper MD, Bartke A (2008) Diet and aging. Cell Metab 8(2):99–104

    Article  CAS  PubMed  Google Scholar 

  • Poulsen MM, Vestergaard PF, Clasen BF, Radko Y, Christensen LP, Stodkilde-Jorgensen H, Moller N, Jessen N, Pedersen SB, Jorgensen JO (2013) High-dose resveratrol supplementation in obese men: an investigator-initiated, randomized, placebo-controlled clinical trial of substrate metabolism, insulin sensitivity, and body composition. Diabetes 62(4):1186–1195

    Article  CAS  PubMed  Google Scholar 

  • Rattan SI (2008) Hormesis in aging. Ageing Res Rev 7(1):63–78

    Article  PubMed  Google Scholar 

  • Rattan SI (2012) Biogerontology: from here to where? The Lord Cohen Medal Lecture-2011. Biogerontology 13(1):83–91

    Article  PubMed  Google Scholar 

  • Robb EL, Page MM, Wiens BE, Stuart JA (2008) Molecular mechanisms of oxidative stress resistance induced by resveratrol: specific and progressive induction of MnSOD. Biochem Biophys Res Commun 367(2):406–412

    Article  CAS  PubMed  Google Scholar 

  • Schumacher U, Adam E, Kretzschmar H, Pfuller U (1994) Binding patterns of mistletoe lectins I, II and III to microglia and Alzheimer plaque glycoproteins in human brains. Acta Histochem 96(4):399–403

    Article  CAS  PubMed  Google Scholar 

  • Seo K, Choi E, Lee D, Jeong DE, Jang SK, Lee SJ (2013) Heat shock factor 1 mediates the longevity conferred by inhibition of TOR and insulin/IGF-1 signaling pathways in C. elegans. Aging Cell 12(6):1073–1081

    Article  CAS  PubMed  Google Scholar 

  • Slack C, Foley A, Partridge L (2012) Activation of AMPK by the putative dietary restriction mimetic metformin is insufficient to extend lifespan in Drosophila. PLoS ONE 7(10):e47699

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wang Y, Deng M, Zhang SY, Zhou ZK, Tian WX (2008) Parasitic loranthus from Loranthaceae rather than Viscaceae potently inhibits fatty acid synthase and reduces body weight in mice. J Ethnopharmacol 118(3):473–478

    Article  CAS  PubMed  Google Scholar 

  • Wilson MA, Shukitt-Hale B, Kalt W, Ingram DK, Joseph JA, Wolkow CA (2006) Blueberry polyphenols increase lifespan and thermotolerance in Caenorhabditis elegans. Aging Cell 5(1):59–68

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Wood JG, Rogina B, Lavu S, Howitz K, Helfand SL, Tatar M, Sinclair D (2004) Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature 430(7000):686–689

    Article  CAS  PubMed  Google Scholar 

  • Yang JS, Nam HJ, Seo M, Han SK, Choi Y, Nam HG, Lee SJ, Kim S (2011) OASIS: online application for the survival analysis of lifespan assays performed in aging research. PLoS ONE 6(8):e23525

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Yu BP, Chung HY (2001) Stress resistance by caloric restriction for longevity. Ann N Y Acad Sci 928:39–47

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Basic Science Research Program through the National Research Foundation of Korea (NRF), funded by the Ministry of Education, Science, and Technology (No. 2012R1A1A2041099).

Author information

Authors and Affiliations

  1. Department of Biological Sciences, Inha University, Inchon, 402-751, Korea

    Shin-Hae Lee, Eun-Ji Lee, Hye-Yeon Lee & Kyung-Jin Min

  2. School of Life and Food Sciences, Handong Global University, Pohang, 791-708, Korea

    Hyo-Sun An & Jong-Bae Kim

  3. Department of Pharmacy, Korea University, Chungnam, Jochiwon, 339-700, Korea

    Yong Woo Jung

  4. Department of Life Sciences, Pohang University of Science and Technology, Pohang, 790-784, Korea

    Eun-Seok Choi, Seon Woo An, Heehwa Son & Seung-Jae Lee

Authors
  1. Shin-Hae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Hyo-Sun An
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yong Woo Jung
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Eun-Ji Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Hye-Yeon Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Eun-Seok Choi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Seon Woo An
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Heehwa Son
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Seung-Jae Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Jong-Bae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Kyung-Jin Min
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kyung-Jin Min.

Additional information

Shin-Hae Lee, Hyo-Sun An and Yong Woo Jung have contributed equally to this study.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lee, SH., An, HS., Jung, Y.W. et al. Korean mistletoe (Viscum album coloratum) extract extends the lifespan of nematodes and fruit flies. Biogerontology 15, 153–164 (2014). https://doi.org/10.1007/s10522-013-9487-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-013-9487-7

Keywords

Search

Navigation