Abstract
Experimentally restricting dietary calories, while maintaining adequate dietary nutrient content, extends lifespan in phylogenetically diverse species; thus suggesting the existence of conserved pathways which can modify lifespan in response to energy intake. However, in some cases the impact on longevity may depend on the quality of the energy source. In Drosophila, restriction of dietary yeast yields considerable lifespan extension whereas isocaloric restriction of dietary sugar yields only modest extension, indicating that other diet-responsive pathways can modify lifespan in this species. In rodents, restricting intake of a single amino acid – methionine – extends lifespan. Here we show that dietary methionine can modify lifespan in adult female, non-virgin Oregon-R strain Drosophila fed a chemically defined media. Compared to a diet containing 0.135% methionine and 15% glucose, high dietary methionine (0.405%) shortened maximum lifespan by 2.33% from 86 to 84 days and mean lifespan by 9.55% from 71.7 to 64.9 days. Further restriction of methionine to 0.045% did not extend maximum lifespan and shortened mean lifespan by 1.95% from 71.1 to 70.3 days. Restricting glucose from 15% to 5% while holding methionine at a concentration of 0.135%, modestly extended maximum lifespan by 5.8% from 86 to 91 days, without extending mean lifespan. All these diet-induced changes were highly significant (log-rank p < 0.0001). Notably, all four diets resulted in considerably longer life spans than those typically reported for flies fed conventional yeast and sugar based diets. Such defined diets can be used to identify lifespan-modifying pathways and specific gene-nutrient interactions in Drosophila.
Similar content being viewed by others
Abbreviations
- IGF-1:
-
Insulin-like growth factor 1
- TOR:
-
Target of rapamycin
References
Avruch J, Lin Y, Long X, Murthy S, Ortiz-Vega S (2005) Recent advances in the regulation of the TOR pathway by insulin and nutrients. Curr Opin Clin Nutr Metab Care 8:67–72
Benevenga NJ, Yeh MH, Lalich JJ (1976) Growth depression and tissue reaction to the consumption of excess dietary methionine and S-methyl-L-cysteine. J Nutr 106:1714–1720
Britton JS, Lockwood WK, Li L, Cohen SM, Edgar BA (2002) Drosophila’s insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev Cell 2:239–249
Brown-Borg HM, Rakoczy SG, Uthus EO (2005) Growth hormone alters methionine and glutathione metabolism in Ames dwarf mice. Mech Ageing Dev 126:389–398
Chapman T, Miyatake T, Smith HK, Partridge L (1998) Interactions of mating, egg production and death rates in females of the Mediterranean fruit fly, Ceratitis capitata. Proc Biol Sci 265:1879–1894
Clancy DJ, Gems D, Hafen E, Leevers SJ, Partridge L (2002) Dietary restriction in long-lived dwarf flies. Science 296:319
Ekperigin HE, Vohra P (1981) Histopathological and biochemical effects of feeding excess dietary methionine to broiler chicks. Avian Dis 25:82–95
Finkelstein JD (1990) Methionine metabolism in mammals. J Nutr Biochem 1:228–237
Finkelstein A, Benevenga NJ (1984) Developmental changes in the metabolism of 3-methylthiopropionate in the rat. J Nutr 114:1622–1629
Gems D, Partridge L (2001) Insulin/IGF signalling and ageing: seeing the bigger picture. Curr Opin Genet Dev 11:287–292
Goldfischer S, Grotsky HW, Chang CH, Berman EL, Richert RR, Karmarkar SD, Roskamp JO, Morecki R (1981) Idiopathic neonatal iron storage involving the liver, pancreas, heart, and endocrine and exocrine glands. Hepatology 1:58–64
Good TP, Tatar M (2001) Age-specific mortality and reproduction respond to adult dietary restriction in Drosophila melanogaster. J Insect Physiol 47:1467–1473
Harper AE, Benevenga NJ, Wohlhueter RM (1970) Effects of ingestion of disproportionate amounts of amino acids. Physiol Rev 50:428–558
Hinton T, Ellis J, Noyes DT (1951) Amino acids and growth factors in a chemically defined medium for Drosophila. Physiol Zool 24:335
Houthoofd K, Braeckman BP, Johnson TE, Vanfleteren JR (2003) Life extension via dietary restriction is independent of the Ins/IGF-1 signalling pathway in Caenorhabditis elegans. Exp Gerontol 38:947–954
Iwasaki K, Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, Yu BP (1988a) The influence of dietary protein source on longevity and age-related disease processes of Fischer rats. J Gerontol 43:B5–B12
Iwasaki K, Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, Yu BP (1988b) Influence of the restriction of individual dietary components on longevity and age-related disease of Fischer rats: the fat component and the mineral component. J Gerontol 43:B13–B21
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
Kimball S, Jefferson L (2006) New functions for amino acids: effects on gene transcription and translation. Am J Clin Nutr 83:500S–507S
Kritchevsky D, Weber MM, Klurfeld DM (1984) Dietary fat versus caloric content in initiation and promotion of 7,12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats. Cancer Res 44:3174–3177
Kumagai H, Katoh S, Hirosawa K, Kimura M, Hishida A, Ikegaya N (2002) Renal tubulointerstitial injury in weanling rats with hyperhomocysteinemia. Kidney Int 62:1219–1228
Long X, Ortiz-Vega S, Lin Y, Avruch J (2005) Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J Biol Chem 280:23433–23436
Longo VD, Finch CE (2003) Evolutionary medicine: from dwarf model systems to healthy centenarians? Science 299:1342–1346
Magwere T, Chapman T, Partridge L (2004) Sex differences in the effect of dietary restriction on life span and mortality rates in female and male Drosophila melanogaster. J Gerontol Ser A Biol Sci Med Sci 59:3–9
Mair W, Goymer P, Pletcher SD, Partridge L (2003) Demography of dietary restriction and death in Drosophila. Science 301:1731–1733
Mair W, Piper MD, Partridge L (2005) Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol 3:e223
Masoro EJ (1990) Assessment of nutritional components in prolongation of life and health by diet. Proc Soc Exp Biol Med 193:31–34
Miller RA, Buehner G, Chang Y, Harper JM, Sigler R, 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
Min KJ, Tatar M (2006a) Restriction of amino acids extends lifespan in Drosophila melanogaster. Mech Ageing Dev 127(7)
Min KJ, Tatar M (2006b) Drosophila diet restriction in practice: do flies consume fewer nutrients? Mech Ageing Dev 127(1):93–96
Murtagh-Mark CM, Reiser KM, Harris R Jr, McDonald RB (1995) Source of dietary carbohydrate affects life span of Fischer 344 rats independent of caloric restriction. J Gerontol Ser A Biol Sci Med Sci 50:B148–154
Ni W, Tsuda Y, Sakono M, Imaizumi K (1998) Dietary soy protein isolate, compared with casein, reduces atherosclerotic lesion area in apolipoprotein E-deficient mice. J Nutr 128:1884–1889
Orentreich N, Matias JR, DeFelice A, Zimmerman JA (1993) Low methionine ingestion by rats extends life span. J Nutr 123:269–274
Orr WC, Mockett RJ, Benes JJ, Sohal RS (2003) Effects of overexpression of copper-zinc and manganese superoxide dismutases, catalase, and thioredoxin reductase genes on longevity in Drosophila melanogaster. J Biol Chem 278:26418–26422
Partridge L, Pletcher SD, Mair W (2005) Dietary restriction, mortality trajectories, risk and damage. Mech Ageing Dev 126:35–41
Piper MD, Mair W, Partridge L (2005) Counting the calories: the role of specific nutrients in extension of life span by food restriction. J Gerontol Ser A Biol Sci Med Sci 60:549–555
Pletcher SD (1999) Model fitting and hypothesis testing for age-specific mortality data. J Evol Biol 12:430–439
Pletcher SD, Khazaeli AA, Curtsinger JW (2000) Why do life spans differ? Partitioning mean longevity differences in terms of age-specific mortality parameters. J Gerontol Ser A Biol Sci Med Sci 55:B381–B389
Pletcher SD, Macdonald SJ, Marguerie R, Certa U, Stearns SC, Goldstein DB, Partridge L (2002) Genome-wide transcript profiles in aging and calorically restricted Drosophila melanogaster. Curr Biol 12:712–723
Richie JP Jr, Leutzinger Y, Parthasarathy S, Malloy V, Orentreich N, Zimmerman JA (1994) Methionine restriction increases blood glutathione and longevity in F344 rats. Faseb J 8:1302–1307
Russo GT, Friso S, Jacques PF, Rogers G, Cucinotta D, Wilson PW, Ordovas JM, Rosenberg IH, Selhub J (2003) Age and gender affect the relation between methylenetetrahydrofolate reductase C677T genotype and fasting plasma homocysteine concentrations in the Framingham offspring study cohort. J Nutr 133:3416–3421
Sang JH (1955) The quantitative nutritional requirements of Drosophila melanogaster. J Exp Biol 33:45
Selhub J (2002) Folate, vitamin B12 and vitamin B6 and one carbon metabolism. J Nutr Health Aging 6:39–42
Selhub J, Jacques PF, Wilson PW, Rush D, Rosenberg IH (1993) Vitamin status and intake as primary determinants of homocysteinemia in an elderly population. Jama 270:2693–2698
Sohal RS, Weindruch R (1996) Oxidative stress, caloric restriction, and aging. Science 273:59–63
Stramentinoli G, Gualano M, Catto E, Algeri S (1977) Tissue levels of S-adenosylmethionine in aging rats. J Gerontol 32:392–394
Stubbs AK, Wheelhouse NM, Lomax MA, Hazlerigg DG (2002) Nutrient-hormone interaction in the ovine liver: methionine supply selectively modulates growth hormone-induced IGF-I gene expression. J Endocrinol 174:335–341
Troen AM, Lutgens E, Smith DE, Rosenberg IH, Selhub J (2003) The atherogenic effect of excess methionine intake. Proc Natl Acad Sci USA 100:15089–15094
Uthus EO, Brown-Borg HM (2003) Altered methionine metabolism in long living Ames dwarf mice. Exp Gerontol 38:491–498
Uthus EO, Brown-Borg HM (2006) Methionine flux to transsulfuration is enhanced in the long living Ames dwarf mouse. Mech Ageing Dev 127:444–450
Villee CA, Bissell HB (1948) Nucleic acids as growth factors in Drosophila. JBC 172(1):59–66
Walker G, Houthoofd K, Vanfleteren JR, Gems D (2005) Dietary restriction in C. elegans: from rate-of-living effects to nutrient sensing pathways. Mech Ageing Dev 126:929–937
Weindruch R, Walford R (1988) The retardation of aging and disease by dietary restriction. Thomas, Springfield, Illinois
Yokota F, Esashi T, Suzue R (1978) Nutritional anemia induced by excess methionine in rat and the alleviative effects of glycine on it. J Nutr Sci Vitaminol 24:527–533
Yui R, Ohno Y, Matsuura ET (2003) Accumulation of deleted mitochondrial DNA in aging Drosophila melanogaster. Genes Genet Syst 78:245–251
Zimmerman JA, Malloy V, Krajcik R, Orentreich N (2003) Nutritional control of aging. Exp Gerontol 38:47–52
Acknowledgements
This research was supported by the U.S. Department of Agriculture cooperative research agreement 58-1950-4-401 and by pilot grant DAX601 from the Jean Mayer USDA Human Nutrition Research Center on Aging. Thanks to Nathalie Dupin, Fabienne LeRoy, Susan Hiller Troen, and Christine Schueller for technical assistance and to Mary Roberts, Isabelle Draper and Robert Jackson for their advice throughout.
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found online at http://dx.doi.org/10.1007/s11357-010-9133-0
About this article
Cite this article
Troen, A.M., French, E.E., Roberts, J.F. et al. Lifespan modification by glucose and methionine in Drosophila melanogaster fed a chemically defined diet. AGE 29, 29–39 (2007). https://doi.org/10.1007/s11357-006-9018-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11357-006-9018-4