The Nutritional Geometry of Aging

  • Stephen J. Simpson
  • David Raubenheimer


There is currently considerable interest in whether dietary restriction prolongs longevity because of caloric restriction or whether more specific nutrient effects are involved. Here it is shown how the development of state-space geometric models in nutrition (the Geometric Framework) has provided a new approach to separating the effects of calories and nutrients. We introduce the models and illustrate their use in three recent studies on insects. Data from these organisms demonstrate that it is not calories per se that drives the relationship between diet and longevity, but rather the ratio of protein to non-protein energy ingested. It is argued that similar geometric analysis is required for mammalian model systems.


Calories Cricket Drosophila Geometric framework Protein 


  1. Ayala, V., Naudi, A., Sanz, A., Caro, P., Portero-Otin, M., Barja, G. and Pamplona, R., 2007. Dietary protein restriction decreases oxidative protein damage, peroxidizability index, and mitochondrial complex I content in rat liver. J Gerontol A Biol Sci Med Sci 62, 352–360.PubMedCrossRefGoogle Scholar
  2. Baur, J. A., Pearson, K. J., Price, N. L., Jamieson, H. A., Lerin, C., Kalra, A., Prabhu, V. V., Allard, J. S., Lopez-Lluch, G., Lewis, K., Pistell, P. J., Poosala, S., Becker, K. G., Boss, O., Gwinn, D., Wang, M. Y., Ramaswamy, S., Fishbein, K. W., Spencer, R. G., Lakatta, E. G., Le Couteur, D., Shaw, R. J., Navas, P., Puigserver, P., Ingram, D. K., de Cabo, R. and Sinclair, D. A., 2006. Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444, 337–342.PubMedCrossRefGoogle Scholar
  3. Bordone, L. and Guarente, L., 2005. Calorie restriction, Sirt1 and metabolism: understanding longevity. Nat Rev Mol Cell Biol 6, 298–305.PubMedCrossRefGoogle Scholar
  4. Butler, R. N. and Sprott, R. L., 2000. Biomarkers of Aging: From Primitive Organisms to Man. International Longevity Center, New York.Google Scholar
  5. Carey, J. R., Harshman, L. G., Liedo, P., Müller, H.-G., Wang, J.-L. and Zhang, Z., 2008. Longevity-fertility trade-offs in the tephritid fruit fly, Anastrepha ludens, across dietary-restriction gradients. Aging Cell 7, 470–477.PubMedCrossRefGoogle Scholar
  6. Cruz-Rivera, E. and Hay, M. E., 2000. Can quantity replace quality? Food choice, compensatory feeding, and fitness of marine mesograzers. Ecology 81, 201–219.CrossRefGoogle Scholar
  7. Dussutour, A. and Simpson, S. J., 2008. Carbohydrate regulation in relation to colony growth in ants. J Exp Biol 211, 2224–2232.PubMedCrossRefGoogle Scholar
  8. Dussutour, A. and Simpson, S. J., 2009. Communal nutrition in ants. Curr Biol 19, 740–744 .Google Scholar
  9. Fanson, B. G., Weldon, C. W., Perez-Staples, D., Simpson, S. J. and Taylor, P. W., 2009. Nutrients, not caloric restriction, extend lifespan in Queensland fruit flies (Bactrocera tryoni). Aging Cell 8, 514–523.Google Scholar
  10. Felton, A. M., Felton, A., Raubenheimer, D., Simpson, S. J., Foley, W. J., Wood, J. T., Wallis, I. R. and Lindenmayer, D. B., 2009. The protein content of food items dictates the total energy intake of a free-ranging primate. Behav Ecol 20, 685–690.Google Scholar
  11. Grandison, R. C., Piper, M. D. W. and Partridge, L., 2009. Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462, 1061–1064.Google Scholar
  12. Guarente, L. and Picard, F., 2005. Calorie restriction – the SIR2 connection. Cell 120, 473–482.PubMedCrossRefGoogle Scholar
  13. Hulbert, A. J., 2008. The links between membrane composition, metabolic rate and lifespan. Comp Biochem Physiol A Mol Integr Physiol 150, 196–203.PubMedCrossRefGoogle Scholar
  14. Hulbert, A. J., Pamplona, R., Buffenstein, R. and Buttemer, W. A., 2007. Life and death: Metabolic rate, membrane composition, and life span of animals. Physiol Rev 87, 1175–1213.PubMedCrossRefGoogle Scholar
  15. Ja, W. W., Carvalho, G. B., Mak, E. M., de la Rosa, N. N., Fang, A. Y., Liong, J. C., Brummel, T. and Benzer, S., 2007. Prandiology of Drosophila and the CAFE assay. PNAS 104, 8253–8256.PubMedCrossRefGoogle Scholar
  16. Kanfi, Y., Shalman, R., Peshti, V., Pilosof, S. N., Gozlan, Y. M., Pearson, K. J., Lerrer, B., Moazed, D., Marine, J. C., de Cabo, R. and Cohen, H. Y., 2008. Regulation of SIRT6 protein levels by nutrient availability. FEBS Lett 582, 2417–2423.PubMedCrossRefGoogle Scholar
  17. Kapahi, P. and Zid, B. M., 2004. TOR pathway: linking nutrient sensing to life span. SAGE KE 36, pe34.Google Scholar
  18. Kapahi, P., Zid, B. M., Harper, T., Koslover, D., Sapin, V. and Benzer, S., 2004. Regulation of lifespan in Drosophila by modulation of genes in the TOR signaling pathway. Curr Biol 14, 885–890.PubMedCrossRefGoogle Scholar
  19. Le Couteur, D. G., Fraser, R., Cogger, V. C. and McLean, A. J., 2002. Hepatic pseudocapillarisation and atherosclerosis in ageing. Lancet 359, 1612–1615.PubMedCrossRefGoogle Scholar
  20. Lee, K. P., Cory, J. S., Wilson, K., Raubenheimer, D. and Simpson, S. J., 2006. Flexible diet choice offsets protein costs of pathogen resistance in a caterpillar. Proc R Soc B Biol Sci 273, 823–829.CrossRefGoogle Scholar
  21. Lee, K. P., Raubenheimer, D. and Simpson, S. J., 2004. The effects of nutritional imbalance on compensatory feeding for cellulose-mediated dietary dilution in a generalist caterpillar. Physiol Entomol 29, 108–117.CrossRefGoogle Scholar
  22. Lee, K. P., Simpson, S. J., Clissold, F. J., Brooks, R., Ballard, J. W., Taylor, P. W., Soran, N. and Raubenheimer, D., 2008. Lifespan and reproduction in Drosophila: new insights from nutritional geometry. PNAS 105, 2498–2503.PubMedCrossRefGoogle Scholar
  23. Mair, W., Piper, M. D. W. and Partridge, L., 2005. Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol 3, 1305–1311.CrossRefGoogle Scholar
  24. Maklakov, A. A., Simpson, S. J., Zajitschek, F., Hall, M., Dessman, J., Clissold, F., Raubenheimer, D., Bonduriansky, R. and Brooks, R. C., 2008. Sex-specific fitness effects of nutrient intake on reproduction and lifespan. Curr Biol 18, 1062–1066.PubMedCrossRefGoogle Scholar
  25. Masoro, E. J., 2006. Caloric restriction and aging: controversial issues. J Gerontol A Biol Sci Med Sci 61, 14–19.PubMedCrossRefGoogle Scholar
  26. Mayntz, D., Nielsen, V. H., Sørensen, A., Toft, S., Raubenheimer, D., Hejlesen, C. and Simpson, S. J., 2009. Balancing of protein and lipid intake by a mammalian carnivore, the mink, Mustela vison. Anim Behav 77, 349–355.CrossRefGoogle Scholar
  27. Mayntz, D., Raubenheimer, D., Salomon, M., Toft, S. and Simpson, S. J., 2005. Nutrient-specific foraging in invertebrate predators. Science 307, 111–113.PubMedCrossRefGoogle Scholar
  28. McLean, A. J. and Le Couteur, D. G., 2004. Aging biology and geriatric clinical pharmacology. Pharmacol Rev 56, 163–184.PubMedCrossRefGoogle Scholar
  29. Miller, R. A., Buehner, G., Chang, Y., Harper, J. M., Sigler, R. and Smith-Wheelock, M., 2005. 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.PubMedCrossRefGoogle Scholar
  30. Orentreich, N., Matias, J. R., DeFelice, A. and Zimmerman, J. A., 1993. Low methionine ingestion by rats extends life span. J Nutr 123, 269–274.PubMedGoogle Scholar
  31. Piper, M. D. W., Mair, W. and Partridge, L., 2005. Counting the calories: the role of specific nutrients in extension of life span by food restriction. J Gerontol A Biol Sci Med Sci 60, 549–555.PubMedCrossRefGoogle Scholar
  32. Povey, S., Cotter, S. C., Simpson, S. J., Lee, K.-P. and Wilson, K., 2009. Can the protein costs of bacterial resistance be offset by altered feeding behaviour? J Anim Ecol 78, 437–446.PubMedCrossRefGoogle Scholar
  33. Powers, R. W. I. I. I., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K. and Fields, S., 2009. Extension of chronological life span in yeast by decreased TOR pathway signaling. Gene Dev 20, 174–184.CrossRefGoogle Scholar
  34. Raubenheimer, D., Lee, K. P. and Simpson, S. J., 2005. Does Bertrand’s rule apply to macronutrients? Proc R Soc B Biol Sci 272, 2429–2434.CrossRefGoogle Scholar
  35. Raubenheimer, D. and Simpson, S. J., 1993. The geometry of compensatory feeding in the locust. Anim Behav 45, 953–964.CrossRefGoogle Scholar
  36. Raubenheimer, D. and Simpson, S. J., 1994. The analysis of nutrient budgets. Funct Ecol 8, 783–791.CrossRefGoogle Scholar
  37. Raubenheimer, D. and Simpson, S. J., 1995. Constructing nutrient budgets. Entomol Exp Appl 77, 99–104.CrossRefGoogle Scholar
  38. Raubenheimer, D. and Simpson, S. J., 1997. Integrative models of nutrient balancing: application to insects and vertebrates. Nutr Res Rev 10, 151–179.PubMedCrossRefGoogle Scholar
  39. Raubenheimer, D. and Simpson, S. J., 2006. The challenge of supplementary feeding: can geometric analysis help save the kakapo? Notornis 53, 100–111.Google Scholar
  40. Raubenheimer, D. and Simpson, S. J., 2009. Nutritional pharmecology: doses, nutrients, toxins, and medicines. Integr Comp Biol 49, 329–337.Google Scholar
  41. Raubenheimer, D., Simpson, S. J. and Mayntz, D., 2009. Nutrition, ecology and nutritional ecology: toward an integrated framework. Funct Ecol 23, 4–16.CrossRefGoogle Scholar
  42. Ross, M. H., 1961. Length of life and nutrition in the rat. J Nutr 75, 197–210.PubMedGoogle Scholar
  43. Ruohonen, K., Simpson, S. J. and Raubenheimer, D., 2007. A new approach to diet optimisation: a reanalysis using European whitefish (Coregonus lavaretus). Aquaculture 267, 147–156.CrossRefGoogle Scholar
  44. Sanz, A., Caro, P. and Barja, G., 2004. Protein restriction without strong caloric restriction decreases mitochondrial oxygen radical production and oxidative DNA damage in rat liver. J Bioenerg Biomembr 36, 545–552.PubMedCrossRefGoogle Scholar
  45. Simpson, S. J., Browne, L. B. and Vangerwen, A. C. M., 1989. The patterning of compensatory sugar feeding in the Australian sheep blowfly. Physiol Entomol 14, 91–105.CrossRefGoogle Scholar
  46. Simpson, S. J. and Raubenheimer, D., 1993. A multi-level analysis of feeding behaviour: the geometry of nutritional decisions. Philos Trans R Soc Lond B Biol Sci 342, 381–402.CrossRefGoogle Scholar
  47. Simpson, S. J. and Raubenheimer, D., 2001. The geometric analysis of nutrient-allelochemical interactions: a case study using locusts. Ecology 82, 422–439.Google Scholar
  48. Simpson, S. J. and Raubenheimer, D., 2005. Obesity: the protein leverage hypothesis. Obesity Rev 6, 133–142.CrossRefGoogle Scholar
  49. Simpson, S. J. and Raubenheimer, D., 2007. Caloric restriction and aging revisited: the need for a geometric analysis of the nutritional bases of aging. J Gerontol A Biol Sci Med Sci 62, 707–713.PubMedCrossRefGoogle Scholar
  50. Simpson, S. J. and Raubenheimer, D., 2009. Macronutrient balance and lifespan. AGING 1, 875–880.Google Scholar
  51. Simpson, S. J., Sibly, R. M., Lee, K. P., Behmer, S. T. and Raubenheimer, D., 2004. Optimal foraging when regulating intake of multiple nutrients. Anim Behav 68, 1299–1311.CrossRefGoogle Scholar
  52. Simpson, S. J. and Simpson, C. L., 1990. The mechanisms of nutritional compensation by phytophagous insects. In Bernays, E. A. (ed), Insect-Plant Interactions, vol. II. CRC Press, Boca Raton, FL.Google Scholar
  53. Skorupa, D. A., Dervisefendic, A., Zwiener, J. and Pletcher, S. D., 2008. Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 7, 478–490.PubMedCrossRefGoogle Scholar
  54. Stock, M. J., 1999. Gluttony and thermogenesis revisited. Int J Obesity 23, 1105–1117.CrossRefGoogle Scholar
  55. Sørensen, A., Mayntz, D., Raubenheimer, D. and Simpson, S. J., 2008. Protein-leverage in mice: the geometry of macronutrient balancing and consequences for fat deposition. Obesity 16, 566–571.PubMedCrossRefGoogle Scholar
  56. Troen, A., French, E. E., Roberts, J. F., Selhub, J., Ordovas, J. M., Parnell, L. D. and Lai, C.-Q., 2007. Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet. Age 29, 29–39.PubMedCrossRefGoogle Scholar
  57. Warbrick-Smith, J., Behmer, S. T., Lee, K. P., Raubenheimer, D. and Simpson, S. J., 2006. Evolving resistance to obesity in an insect. PNAS 103, 14045–14049.PubMedCrossRefGoogle Scholar
  58. Weindruch, R. and Walford, R. L., 1988. The Retardation of Aging and Disease by Dietary Restriction. Charles C Thomas, Springfield, IL.Google Scholar
  59. Wong, R., Piper, M. D. W., Blanc, E. and Partridge, L., 2008. Pitfalls of measuring feeding rate in the fruit fly Drosophila melanogaster. Nat Meth 5, 214–215.CrossRefGoogle Scholar
  60. Zanotto, F. P., Gouveia, S. M., Simpson, S. J., Raubenheimer, D. and Calder, P. C., 1997. Nutritional homeostasis in locusts: is there a mechanism for increased energy expenditure during carbohydrate overfeeding? J Exp Biol 200, 2437–2448.PubMedGoogle Scholar
  61. Zimmerman, J. A., Malloy, V., Krajcik, R. and Orentreich, N., 2003. Nutritional control of aging. Exp Gerontol 38, 47–52.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2010

Authors and Affiliations

  • Stephen J. Simpson
    • 1
  • David Raubenheimer
    • 2
  1. 1.School of Biological Sciences, The University of SydneySydneyAustralia
  2. 2.Institute of Natural Sciences, Massey UniversityAlbanyNew Zealand

Personalised recommendations