AGE

, Volume 35, Issue 1, pp 69–81 | Cite as

The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

  • Chunxu Wang
  • Charles T. Wheeler
  • Thomas Alberico
  • Xiaoping Sun
  • Jeanne Seeberger
  • Mara Laslo
  • Edward Spangler
  • Bradley Kern
  • Rafael de Cabo
  • Sige Zou
Article

Abstract

Resveratrol, a polyphenolic compound, has been shown to extend lifespan in different organisms. Emerging evidence suggests that the prolongevity effect of resveratrol depends on dietary composition. However, the mechanisms underlying the interaction of resveratrol and dietary nutrients in modulating lifespan remain elusive. Here, we investigated the effect of resveratrol on lifespan of Drosophila melanogaster fed diets differing in the concentrations of sugar, yeast extract, and palmitic acid representing carbohydrate, protein, and fat, respectively. Resveratrol at up to 200 μM in diets did not affect lifespan of wild-type female flies fed a standard, restricted or high sugar–low protein diet, but extended lifespan of females fed a low sugar–high protein diet. Resveratrol at 400 μM extended lifespan of females fed a high-fat diet. Lifespan extension by resveratrol was associated with downregulation of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. Furthermore, resveratrol increased lifespan of superoxide dismutase 1 (sod1) knockdown mutant females fed a standard or high-fat diet. No lifespan extension by resveratrol was observed in wild-type and sod1 knockdown males under the culture conditions in this study. Our results suggest that the gender-specific prolongevity effect of resveratrol is influenced by dietary composition and resveratrol promotes the survival of flies by modulating genetic pathways that can reduce cellular damage. This study reveals the context-dependent effect of resveratrol on lifespan and suggests the importance of dietary nutrients in implementation of effective aging interventions using dietary supplements.

Keywords

Resveratrol Lifespan Dietary composition Aging intervention Superoxide dismutase 1 Oxidative stress 

Abbreviations

sod1

Superoxide dismutase 1

CR

Calorie restriction

DR

Dietary restriction

IR

Inverted repeat

Mexfly

Mexican fruit fly

qPCR

Quantitative polymerase chain reaction

SY

Sugar and yeast extract

dIlp3

Drosophila insulin-like peptide 3

dIlp5

Drosophila insulin-like peptide 5

gstD1

Glutathione S transferase D1

hsp68

Heat shock protein 68

Prx

Peroxiredoxin

JNK

Jun kinase

RNAi

RNA interference

AMPK

AMP-activated protein kinase

IGF-1

Insulin-like growth factor 1

Notes

Acknowledgements

This study was supported by funding from the Intramural Research Program of the National Institute on Aging, NIH to SZ. CXW was supported by a scholarship sponsored by the Chinese Scholarship Council.

References

  1. Allard JS, Perez E, Zou S, de Cabo R (2009) Dietary activators of Sirt1. Mol Cell Endocrinol 299(1):58–63. doi: 10.1016/j.mce.2008.10.018 PubMedCrossRefGoogle Scholar
  2. Ashburner M, Golic KG, Hawley RS (eds) (2005) Drosophila: a laboratory handbook, 2nd edn. Cold Spring Harbor Laboratory Press, Woodbury, NYGoogle Scholar
  3. Bass TM, Grandison RC, Wong R, Martinez P, Partridge L, Piper MD (2007a) Optimization of dietary restriction protocols in Drosophila. J Gerontol A Biol Sci Med Sci 62(10):1071–1081PubMedCrossRefGoogle Scholar
  4. Bass TM, Weinkove D, Houthoofd K, Gems D, Partridge L (2007b) Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans. Mech Ageing Dev 128(10):546–552PubMedCrossRefGoogle Scholar
  5. Baur JA (2010) Resveratrol, sirtuins, and the promise of a DR mimetic. Mech Ageing Dev 131(4):261–269PubMedCrossRefGoogle Scholar
  6. Baur JA, Sinclair DA (2006) Therapeutic potential of resveratrol: the in vivo evidence. Nat Rev Drug Discov 5(6):493–506PubMedCrossRefGoogle Scholar
  7. 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):337–342PubMedCrossRefGoogle Scholar
  8. Boyd O, Weng P, Sun X, Alberico T, Laslo M, Obenland DM, Kern B, Zou S (2011) Nectarine promotes longevity in Drosophila melanogaster. Free Radic Biol Med 50(11):1669–1678PubMedCrossRefGoogle Scholar
  9. Bross TG, Rogina B, Helfand SL (2005) Behavioral, physical, and demographic changes in Drosophila populations through dietary restriction. Aging Cell 4(6):309–317PubMedCrossRefGoogle Scholar
  10. Broughton SJ, Piper MD, Ikeya T, Bass TM, Jacobson J, Driege Y, Martinez P, Hafen E, Withers DJ, Leevers SJ, Partridge L (2005) Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci USA 102(8):3105–3110. doi: 10.1073/pnas.0405775102 PubMedCrossRefGoogle Scholar
  11. Carey JR, Harshman LG, Liedo P, Muller HG, Wang JL, Zhang Z (2008) Longevity–fertility trade-offs in the tephritid fruit fly, Anastrepha ludens, across dietary-restriction gradients. Aging Cell 7(4):470–477PubMedCrossRefGoogle Scholar
  12. Chan AY, Dolinsky VW, Soltys CL, Viollet B, Baksh S, Light PE, Dyck JR (2008) Resveratrol inhibits cardiac hypertrophy via AMP-activated protein kinase and Akt. J Biol Chem 283(35):24194–24201PubMedCrossRefGoogle Scholar
  13. Colman RJ, Anderson RM, Johnson SC, Kastman EK, Kosmatka KJ, Beasley TM, Allison DB, Cruzen C, Simmons HA, Kemnitz JW, Weindruch R (2009) Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325(5937):201–204PubMedCrossRefGoogle Scholar
  14. Desai AK, Grossberg GT, Chibnall JT (2010) Healthy brain aging: a road map. Clin Geriatr Med 26(1):1–16PubMedCrossRefGoogle Scholar
  15. Fanson BG, Weldon CW, Perez-Staples D, Simpson SJ, Taylor PW (2009) Nutrients, not caloric restriction, extend lifespan in Queensland fruit flies (Bactrocera tryoni). Aging Cell 8(5):514–523PubMedCrossRefGoogle Scholar
  16. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span—from yeast to humans. Science 328(5976):321–326PubMedCrossRefGoogle Scholar
  17. Frankel S, Ziafazeli T, Rogina B (2011) dSir2 and longevity in Drosophila. Exp Gerontol 46(5):391–396PubMedCrossRefGoogle Scholar
  18. Guarente L (2007) Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol 72:483–488. doi: 10.1101/sqb.2007.72.024 PubMedCrossRefGoogle Scholar
  19. 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):191–196PubMedCrossRefGoogle Scholar
  20. Ingram DK, Roth GS, Lane MA, Ottinger MA, Zou S, de Cabo R, Mattison JA (2006) The potential for dietary restriction to increase longevity in humans: extrapolation from monkey studies. Biogerontology 7(3):143–148PubMedCrossRefGoogle Scholar
  21. Ja WW, Carvalho GB, Mak EM, de la Rosa NN, Fan AY, Liong AY, Brummel T, Benzer S (2007) Prandiology of Drosophila and the CAFE assay. Proc Natl Acad Sci USA 104(20):8253–8256PubMedCrossRefGoogle Scholar
  22. Kaeberlein M, McDonagh T, Heltweg B, Hixon J, Westman EA, Caldwell SD, Napper A, Curtis R, DiStefano PS, Fields S, Bedalov A, Kennedy BK (2005) Substrate-specific activation of sirtuins by resveratrol. J Biol Chem 280(17):17038–17045PubMedCrossRefGoogle Scholar
  23. Karpac J, Jasper H (2009) Insulin and JNK: optimizing metabolic homeostasis and lifespan. Trends Endocrinol Metab 20(3):100–106. doi: 10.1016/j.tem.2008.11.004 PubMedCrossRefGoogle Scholar
  24. Lee KP, Simpson SJ, Clissold FJ, Brooks R, Ballard JW, Taylor PW, Soran N, Raubenheimer D (2008) Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proc Natl Acad Sci USA 105(7):2498–2503PubMedCrossRefGoogle Scholar
  25. Lee SM, Yang H, Tartar DM, Gao B, Luo X, Ye SQ, Zaghouani H, Fang D (2011) Prevention and treatment of diabetes with resveratrol in a non-obese mouse model of type 1 diabetes. Diabetologia 54(5):1136–1146PubMedCrossRefGoogle Scholar
  26. Liao CY, Rikke BA, Johnson TE, Diaz V, Nelson JF (2010) Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging Cell 9(1):92–95. doi: 10.1111/j.1474-9726.2009.00533.x PubMedCrossRefGoogle Scholar
  27. Lithgow GJ, Gill MS, Olsen A, Sampayo JN (2005) Pharmacological intervention in invertebrate aging. Age 27(3):213–223CrossRefGoogle Scholar
  28. Mair W, Piper MD, Partridge L (2005) Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol 3(7):e223PubMedCrossRefGoogle Scholar
  29. Martin I, Jones MA, Grotewiel M (2009) Manipulation of Sod1 expression ubiquitously, but not in the nervous system or muscle, impacts age-related parameters in Drosophila. FEBS Lett 583(13):2308–2314. doi: 10.1016/j.febslet.2009.06.023 PubMedCrossRefGoogle Scholar
  30. Masoro EJ (2009) Caloric restriction-induced life extension of rats and mice: a critique of proposed mechanisms. Biochim Biophys Acta 1790(10):1040–1048. doi: 10.1016/j.bbagen.2009.02.011 PubMedCrossRefGoogle Scholar
  31. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH (2007) Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450(7170):712–716PubMedCrossRefGoogle Scholar
  32. Obrenovich ME, Nair NG, Beyaz A, Aliev G, Reddy VP (2010) The role of polyphenolic antioxidants in health, disease, and aging. Rejuvenation Res 13(6):631–643PubMedCrossRefGoogle Scholar
  33. 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. doi: 10.1016/j.cmet.2008.06.011 PubMedCrossRefGoogle Scholar
  34. Piper MD, Partridge L, Raubenheimer D, Simpson SJ (2011) Dietary restriction and aging: a unifying perspective. Cell Metab 14(2):154–160PubMedCrossRefGoogle Scholar
  35. Pirola L, Frojdo S (2008) Resveratrol: one molecule, many targets. IUBMB Life 60(5):323–332. doi: 10.1002/iub.47 PubMedCrossRefGoogle Scholar
  36. Radyuk SN, Sohal RS, Orr WC (2003) Thioredoxin peroxidases can foster cytoprotection or cell death in response to different stressors: over- and under-expression of thioredoxin peroxidase in Drosophila cells. Biochem J 371(Pt 3):743–752. doi: 10.1042/BJ20021522 PubMedCrossRefGoogle Scholar
  37. Salmon AB, Richardson A, Perez VI (2010) Update on the oxidative stress theory of aging: does oxidative stress play a role in aging or healthy aging? Free Radic Biol Med 48(5):642–655PubMedCrossRefGoogle Scholar
  38. Skorupa DA, Dervisefendic A, Zwiener J, Pletcher SD (2008) Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 7(4):478–490. doi: 10.1111/j.1474-9726.2008.00400.x PubMedCrossRefGoogle Scholar
  39. Sun X, Seeberger J, Alberico T, Wang C, Wheeler CT, Schauss AG, Zou S (2010) Acai palm fruit (Euterpe oleracea Mart.) pulp improves survival of flies on a high fat diet. Exp Gerontol 45(3):243–251PubMedCrossRefGoogle Scholar
  40. Szkudelska K, Szkudelski T (2010) Resveratrol, obesity and diabetes. Eur J Pharmacol 635(1–3):1–8PubMedCrossRefGoogle Scholar
  41. Valenzano DR, Terzibasi E, Genade T, Cattaneo A, Domenici L, Cellerino A (2006) Resveratrol prolongs lifespan and retards the onset of age-related markers in a short-lived vertebrate. Curr Biol 16(3):296–300PubMedCrossRefGoogle Scholar
  42. Wang MC, Bohmann D, Jasper H (2005) JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell 121(1):115–125PubMedCrossRefGoogle Scholar
  43. Wood ZA, Poole LB, Karplus PA (2003) Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300(5619):650–653. doi: 10.1126/science.1080405300/5619/650 PubMedCrossRefGoogle Scholar
  44. 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):686–689PubMedCrossRefGoogle Scholar
  45. Zeng C, Du Y, Alberico T, Seeberger J, Sun X, Zou S (2011) Gender-specific prandial response to dietary restriction and oxidative stress in Drosophila melanogaster. Fly 5(3):174–180PubMedCrossRefGoogle Scholar
  46. Zou S, Sinclair J, Wilson MA, Carey JR, Liedo P, Oropeza A, Kalra A, de Cabo R, Ingram DK, Longo DL, Wolkow CA (2007) Comparative approaches to facilitate the discovery of prolongevity interventions: effects of tocopherols on lifespan of three invertebrate species. Mech Ageing Dev 128(2):222–226PubMedCrossRefGoogle Scholar
  47. Zou S, Carey JR, Liedo P, Ingram DK, Muller HG, Wang JL, Yao F, Yu B, Zhou A (2009) The prolongevity effect of resveratrol depends on dietary composition and calorie intake in a tephritid fruit fly. Exp Gerontol 44(6–7):472–476. doi: 10.1016/j.exger.2009.02.011 PubMedCrossRefGoogle Scholar
  48. Zou S, Carey JR, Liedo P, Ingram DK, Yu B, Ghaedian R (2010) Prolongevity effects of an oregano and cranberry extract are diet dependent in the Mexican fruit fly (Anastrepha ludens). J Gerontol A Biol Sci 65(1):41–50CrossRefGoogle Scholar
  49. Zou S, Carey JR, Liedo P, Ingram DK, Yu B (2011) Prolongevity effects of a botanical with oregano and cranberry extracts in Mexican fruit flies: examining interactions of diet restriction and age. Age (in press)Google Scholar

Copyright information

© American Aging Association (outside the USA) 2011

Authors and Affiliations

  • Chunxu Wang
    • 1
    • 2
  • Charles T. Wheeler
    • 1
  • Thomas Alberico
    • 1
  • Xiaoping Sun
    • 1
  • Jeanne Seeberger
    • 1
  • Mara Laslo
    • 1
  • Edward Spangler
    • 1
  • Bradley Kern
    • 1
  • Rafael de Cabo
    • 1
  • Sige Zou
    • 1
    • 3
  1. 1.Laboratory of Experimental GerontologyNational Institute on AgingBaltimoreUSA
  2. 2.Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanPeople’s Republic of China
  3. 3.Functional Genomics Unit, Laboratory of Experimental GerontologyNational Institute on AgingBaltimoreUSA

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