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Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila


Dietary restriction extends healthy lifespan in diverse organisms and reduces fecundity1,2. It is widely assumed to induce adaptive reallocation of nutrients from reproduction to somatic maintenance, aiding survival of food shortages in nature3,4,5,6. If this were the case, long life under dietary restriction and high fecundity under full feeding would be mutually exclusive, through competition for the same limiting nutrients. Here we report a test of this idea in which we identified the nutrients producing the responses of lifespan and fecundity to dietary restriction in Drosophila. Adding essential amino acids to the dietary restriction condition increased fecundity and decreased lifespan, similar to the effects of full feeding, with other nutrients having little or no effect. However, methionine alone was necessary and sufficient to increase fecundity as much as did full feeding, but without reducing lifespan. Reallocation of nutrients therefore does not explain the responses to dietary restriction. Lifespan was decreased by the addition of amino acids, with an interaction between methionine and other essential amino acids having a key role. Hence, an imbalance in dietary amino acids away from the ratio optimal for reproduction shortens lifespan during full feeding and limits fecundity during dietary restriction. Reduced activity of the insulin/insulin-like growth factor signalling pathway extends lifespan in diverse organisms7, and we find that it also protects against the shortening of lifespan with full feeding. In other organisms, including mammals, it may be possible to obtain the benefits to lifespan of dietary restriction without incurring a reduction in fecundity, through a suitable balance of nutrients in the diet.

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Figure 1: Amino acids mediate lifespan and fecundity changes in fly dietary restriction.
Figure 2: Essential amino acids cause the dietary restriction effect.
Figure 3: Methionine is necessary and sufficient to increase dietary restriction fecundity.
Figure 4: Amino acids, insulin signalling and dietary restriction.


  1. 1

    Weindruch, R. & Walford, R. L. The Retardation of Aging and Disease by Dietary Restriction (Thomas, 1988)

    Google Scholar 

  2. 2

    Partridge, L., Gems, D. & Withers, D. J. Sex and death: what is the connection? Cell 120, 461–472 (2005)

    CAS  Article  Google Scholar 

  3. 3

    Holliday, R. Food, reproduction and longevity: is the extended lifespan of calorie-restricted animals an evolutionary adaptation? Bioessays 10, 125–127 (1989)

    CAS  Article  Google Scholar 

  4. 4

    Williams, G. C. Natural selection, the costs of reproduction, and a refinement of Lack’s principle. Am. Nat. 100, 687–690 (1966)

    Article  Google Scholar 

  5. 5

    Kirkwood, T. B. Evolution of ageing. Nature 270, 301–304 (1977)

    CAS  ADS  Article  Google Scholar 

  6. 6

    Mair, W. & Dillin, A. Aging and survival: the genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 77, 727–754 (2008)

    CAS  Article  Google Scholar 

  7. 7

    Russell, S. J. & Kahn, C. R. Endocrine regulation of ageing. Nature Rev. Mol. Cell Biol. 8, 681–691 (2007)

    CAS  Article  Google Scholar 

  8. 8

    Kaeberlein, M., Burtner, C. R. & Kennedy, B. K. Recent developments in yeast aging. PLoS Genet. 3, e84 (2007)

    Article  Google Scholar 

  9. 9

    Piper, M. D. & Bartke, A. Diet and aging. Cell Metab. 8, 99–104 (2008)

    CAS  Article  Google Scholar 

  10. 10

    Colman, R. J. et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325, 201–204 (2009)

    CAS  ADS  Article  Google Scholar 

  11. 11

    De Marte, M. L. & Enesco, H. E. Influence of low tryptophan diet on survival and organ growth in mice. Mech. Ageing Dev. 36, 161–171 (1986)

    CAS  Article  Google Scholar 

  12. 12

    Zimmerman, J. A. et al. Nutritional control of aging. Exp. Gerontol. 38, 47–52 (2003)

    CAS  Article  Google Scholar 

  13. 13

    Miller, R. A. et al. Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4, 119–125 (2005)

    CAS  Article  Google Scholar 

  14. 14

    Klass, M. R. Aging in the nematode Caenorhabditis elegans: major biological and environmental factors influencing life span. Mech. Ageing Dev. 6, 413–429 (1977)

    CAS  Article  Google Scholar 

  15. 15

    Chapman, T. & Partridge, L. Female fitness in Drosophila melanogaster: an interaction between the effect of nutrition and of encounter rate with males. Proc. R. Soc. Lond. B 263, 755–759 (1996)

    CAS  ADS  Article  Google Scholar 

  16. 16

    Selesniemi, K., Lee, H. J. & Tilly, J. L. Moderate caloric restriction initiated in rodents during adulthood sustains function of the female reproductive axis into advanced chronological age. Aging Cell 7, 622–629 (2008)

    CAS  Article  Google Scholar 

  17. 17

    Harrison, D. E. & Archer, J. R. Natural selection for extended longevity from food restriction. Growth Dev. Aging 53, 3–6 (1989)

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 18

    Mair, W., Piper, M. D. & Partridge, L. Calories do not explain extension of lifespan by dietary restriction in Drosophila . PLoS Biol. 7, e223 (2005)

    Article  Google Scholar 

  19. 19

    Wong, R. et al. Quantification of food intake in Drosophila . PLoS ONE 4, e6063 (2009)

    ADS  Article  Google Scholar 

  20. 20

    Piper, M. D. & Partridge, L. Dietary restriction in Drosophila: Delayed aging or experimental artefact? PLoS Genet. 3, e57 (2007)

    Article  Google Scholar 

  21. 21

    Spieth, H. T. Courtship behaviour in Drosophila . Annu. Rev. Entomol. 19, 385–405 (1974)

    CAS  Article  Google Scholar 

  22. 22

    Skorupa, D. A. et al. Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster . Aging Cell 7, 478–490 (2008)

    CAS  Article  Google Scholar 

  23. 23

    Lee, K. P. et al. Ageing and reproduction in Drosophila: new insights from nutritional geometry. Proc. Natl Acad. Sci. USA 105, 2498–2503 (2008)

    CAS  ADS  Article  Google Scholar 

  24. 24

    Bass, T. M. et al. Optimization of dietary restriction protocols in Drosophila . J. Gerontol. A 62, 1071–1081 (2007)

    Article  Google Scholar 

  25. 25

    Sang, J. H. & King, R. C. Nutritional requirements of axenically cultured Drosophila melanogaster adults. J. Exp. Biol. 38, 793–809 (1961)

    CAS  Google Scholar 

  26. 26

    O’Brien, D. M. et al. Use of stable isotopes to examine how dietary restriction extends Drosophila lifespan. Curr. Biol. 18, R155–R156 (2008)

    Article  Google Scholar 

  27. 27

    Fernandez, R. et al. The Drosophila insulin receptor homolog: a gene essential for embryonic development encodes two receptor isoforms with different signaling potential. EMBO J. 14, 3373–3384 (1995)

    CAS  Article  Google Scholar 

  28. 28

    Ikeya, T. et al. The endosymbiont Wolbachia increases insulin/IGF-like signalling in Drosophila. Proc. R. Soc. B 276, 3799–3807 (2009)

    CAS  Article  Google Scholar 

  29. 29

    Millward, D. J. et al. Protein quality assessment: impact of expanding understanding of protein and amino acid needs for optimal health. Am. J. Clin. Nutr. 87, 1576S–1081S (2008)

    CAS  Article  Google Scholar 

  30. 30

    Ikeya, T. et al. Nutrient-dependent expression of insulin-like peptides from neuroendocrine cells in the CNS contributes to growth regulation in Drosophila . Curr. Biol. 12, 1293–1300 (2002)

    CAS  Article  Google Scholar 

  31. 31

    Lange, H. C. & Heijnen, J. J. Statistical reconciliation of the elemental and molecular biomass composition of Saccharomyces cerevisiae . Biotechnol. Bioeng. 75, 334–344 (2001)

    CAS  Article  Google Scholar 

  32. 32

    Sang, J. H. in The Genetics and Biology of Drosophila (eds Ashburner, M. & Wright, T. R. F.) 159–192 (Academic, 1978)

    Google Scholar 

  33. 33

    Grandison, R. C. et al. Effect of a standardised dietary restriction protocol on multiple laboratory strains of Drosophila melanogaster . PLoS ONE 4, e4067 (2009)

    ADS  Article  Google Scholar 

  34. 34

    Clancy, D. J. & Kennington, W. J. A simple method to achieve consistent larval density in bottle cultures. Drosoph. Inf. Serv. 84, 168–169 (2001)

    Google Scholar 

  35. 35

    R Development Core Team. R: A Language and Environment for Statistical Computing. The R Project for Statistical Computing〉 (2005)

  36. 36

    Crawley, M. J. Statistics: An Introduction Using R 103–124 (Wiley, 2005)

    Book  Google Scholar 

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We acknowledge funding from a Wellcome Trust Strategic Award to L.P. (M.D.W.P. and L.P.) and Research into Ageing (R.C.G. and L.P.). We would also like to thank M. Hoddinott for technical support as well as S. Pletcher and E. Blanc for assistance with statistical analyses.

Author Contributions The project was conceived by M.D.W.P. and L.P., and the experiments were designed by R.C.G., M.D.W.P. and L.P. The experiments were performed and analysed by R.C.G. and M.D.W.P. The manuscript was written by R.C.G., M.D.W.P. and L.P.

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Correspondence to Linda Partridge.

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Grandison, R., Piper, M. & Partridge, L. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462, 1061–1064 (2009).

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