Drosophila lifespan control by dietary restriction independent of insulin‐like signaling

Abstract

Summary Reduced insulin/insulin‐like growth factor (IGF) signaling may be a natural way for the reduction of dietary nutrients to extend lifespan. While evidence challenging this hypothesis is accumulating with Caenorhabditis elegans , for Drosophila melanogaster it is still thought that insulin/IGF and the mechanisms of dietary restriction (DR) might as yet function through overlapping mechanisms. Here, we aim to understand this potential overlap. We found that over‐expression of dFOXO in head fat body extends lifespan and reduces steady‐state mRNA abundance of insulin‐like peptide‐2 under conditions of high dietary yeast, but not when yeast is limiting. In contrast, conditions of DR that increase lifespan change only insulin‐like peptide‐5 ( ilp5 ) mRNA abundance. Thus, reduction of ilp5 mRNA is associated with longevity extension by DR, while reduction of insulin‐like peptide‐2 is associated with the diet‐dependent effects of FOXO over‐expression upon lifespan. To assess whether reduction of ilp5 is required for DR to extend lifespan, we blocked its diet‐dependent change with RNAi. Loss of the ilp5 dietary response did not diminish the capacity of DR to extend lifespan. Finally, we assessed the capacity of DR to extend lifespan in the absence of dFOXO, the insulin/IGF‐responsive transcription factor. As with the knockdown of ilp5 diet responsiveness, DR was equally effective among genotypes with and without dFOXO. It is clear from many Drosophila studies that insulin/IGF mediates growth and metabolic responses to nutrition, but we now find no evidence that this endocrine system mediates the interaction between dietary yeast and longevity extension.

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References 33

1. 1.

   Bartke A, Wright C, Mattison JA, Ingram DK, Miller RA, Roth GS. Extending the life span of long-lived mice. Nature. 2001;414:412.

   Not in our library10.1038/35106646

2. 2.

   Bonkowski MS, Rocha JS, Masternak MM, Al Regaiey KA, Bartke A. Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction. Proc. Natl. Acad. Sci. USA. 2006;103:7901-7905.

   Not in our library10.1073/pnas.0600161103

3. 3.

   Broughton SJ, Piper MDW, Ikeya T, Bass TM, Jacobson J, Driege Y, Martinez P, Hafen E, Withers DJ, Leevers SJ, Partridge L. Longer life span, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc. Natl. Acad. Sci. USA. 2005;102:3105-3110.

   Not in our library10.1073/pnas.0405775102

4. 4.

   Buch S, Melcher C, Bauer M, Katzenberger J, Pankratz MJ. Opposing effects of dietary protein and sugar regulate a transcriptional target of Drosophila insulin-like peptide signaling. Curr. Biol. 2008.

   Not in our library10.1016/j.cmet.2008.02.012

5. 5.

   Carvalho GB, Kapahi P, Benzer S. Direct quantification of food intake reveals compensatory ingestion upon dietary restriction in Drosophila. Nat. Methods. 2005;2:813-815.

   Not in our library10.1038/nmeth798

6. 6.

   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. 1996;263:755-759.

   Not in our library10.1098/rspb.1996.0113

7. 7.

   Chippindale AK, Leroi AM, Kim SB, Rose MR. Phenotypic plasticity and selection in Drosophila life-history evolution. I. Nutrition and the cost of reproduction. J. Evol. Biol. 1993;6:171-193.

   Not in our library

8. 8.

   Clancy DJ, Gems D, Harshman LG, Oldham S, Stocker H, Hafen E, Leevers SJ, Partridge L. Extension of life-span by loss of CHICO, a Drosophila insulin receptor substrate protein. Science. 2001;292:104-106.

   Not in our library10.1126/science.1057991

9. 9.

   Clancy DJ, Gems D, Hafen E, Leevers SJ, Partridge L. Dietary restriction in long-lived dwarf flies. Science. 2002;296:319.

   Not in our library10.1126/science.1069366

10. 10.

    Gershman B, Puig O, Hang L, Peitzsch RM, Tatar M, Garofalo RS. High-resolution dynamics of the transcriptional response to nutrition in Drosophila: a key role for dFOXO. Physiol. Genomics. 2007;29:24-34.

    Not in our library10.1152/physiolgenomics.00061.2006

11. 11.

    Giannakou ME, Goss M, Junger MA, Hafen E, Leevers SJ, Partridge L. Long-lived Drosophila with overexpressed dFOXO in adult fat body. Science. 2005;307:675.

    Not in our library10.1126/science.1098219

12. 12.

    Houthoofd K, Braeckman BP, Johnson TE, Vanfleteren JR. Life extension via dietary restriction is independent of the Ins/IGF-1 signaling pathway in Caenorhabditis elegans. Exp. Gerontol. 2003;38:947-954.

    Not in our library10.1016/s0531-5565(03)00161-x

13. 13.

    Houthoofd K, Gems D, Johnson TE, Vanfleteren JR. Dietary restriction in the nematode Caenorhabditis elegans. Interdiscip. Top. Gerontol. 2007;35:98-114.

    Not in our library10.1159/000096558

14. 14.

    Hwangbo DS, Gershman B, Tu MP, Palmer MR, Tatar M. Drosophila dFOXO controls life span and regulates insulin signaling in brain and fat body. Nature. 2004;429:562-566.

    Not in our library10.1038/nature02549

15. 15.

    Junger MA, Rintelen F, Stocker H, Wasserman DA, Vegh M, Radimerski T, Greenberg ME, Hafen E. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J. Biol. 2003;2(3):20.

    Not in our library10.1186/1475-4924-2-20

16. 16.

    Lakowski B, Hekimi S. The genetics of caloric restriction in Caenorhabditis elegans. Proc. Natl. Acad. Sci. USA. 1998;95:13091-13096.

    Not in our library10.1073/pnas.95.22.13091

17. 17.

    Libert S, Zwiener J, Chu X, Vanvoorhies W, Roman G, Pletcher SD. Regulation of Drosophila life span by olfaction and food-derived odors. Science. 2007;315:1133-1137.

    Not in our library10.1126/science.1136610

18. 18.

    Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2 (-Delta Delta C (T) method. Methods. 2001;25:402-408.

    Not in our library10.1006/meth.2001.1262

19. 19.

    Mobbs CV, Yen K, Hof PR. Mechanisms of Dietary Restriction in Aging and Disease. 2007;35.

    Not in our library

20. 20.

    Panowski SH, Wolff S, Aguilaniu H, Durieux J, Dillin A. PHA-4/Foxa mediates diet-restriction-induced longevity of C. elegans. Nature. 2007;447:550-555.

    Not in our library10.1038/nature05837

21. 21.

    Parmer MKB, Machin D. Survival Analysis: A Practical Approach. 1995.

    Not in our library

22. 22.

    Partridge L, Piper MDW, Mair W. Dietary restriction in Drosophila. Mech. Ageing Dev. 2005;126:938-950.

    Not in our library10.1016/j.mad.2005.03.023

23. 23.

    Roman G, Endo K, Zong L, Davis RL. P{Switch}, a system for spatial and temporal control of gene expression in Drosophila melanogaster. Proc. Natl. Acad. Sci. USA. 2001;98:12602-12607.

    Not in our library10.1073/pnas.221303998

24. 24.

    Sambrook J, Russell D. Molecular Cloning: A Laboratory Manual. 2001.

    Not in our library

25. 25.

    Tatar M. Transgenes in the analysis of life span and fitness. Am. Nat. 1999;154:S67-S81.

    Not in our library10.1086/303284

26. 26.

    Tatar M. Diet restriction in Drosophila melanogaster: design and analysis. Interdiscip. Top. Gerontol. 2007;35:115-136.

    Not in our library10.1159/000096559

27. 27.

    Tatar M, Kopelman A, Epstein D, Tu M-P, Yin C-M, Garofalo RS. A mutant Drosophila insulin receptor homolog that extends life span and impairs neuroendocrine function. Science. 2001;292:107-110.

    Not in our library10.1126/science.1057987

28. 28.

    Tu M-P, Epstein D, Tatar M. The demography of slow aging in male and female Drosophila mutant for the insulin-receptor substrate homolog chico. Aging Cell. 2002;1:75-80.

    Not in our library10.1046/j.1474-9728.2002.00010.x

29. 29.

    Walker G, Houthoofd K, Vanfleteren JR, Gems D. Dietary restriction in C. elegans: from rate-of-living effects to nutrient sensing pathways. Mech. Ageing Dev. 2005;26:929-937.

    Not in our library10.1016/j.mad.2005.03.014

30. 30.

    Wang MC, Bohmann D, Jasper H. JNK extends life span and limits growth by antagonizing cellular and organism-wide responses to insulin signaling. Cell. 2005;121:115-125.

    Not in our library10.1016/j.cell.2005.02.030

31. 31.

    Weber K, Johnson N, Champlin D, Patty A. Many P-element insertions affect wing shape in Drosophila melanogaster. Genetics. 2005;169:1461-1475.

    Not in our library10.1534/genetics.104.027748

32. 32.

    Weindruch R, Walford RL, Fligiel S, Guthrie D. The retardation of aging by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr. 1986;116:641-654.

    Not in our library10.1093/jn/116.4.641

33. 33.

    Wessells RJ, Fitzgerald E, Cypser JR, Tatar M, Bodmer R. Insulin regulation of heart function in aging Drosophila. Nat. Genet. 2004;36:1275-1281.

    Not in our library10.1038/ng1476

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