Abstract
The “Green Theory” of aging proposes that organismal lifespan is limited by the failure to repair molecular damage generated by a broad range of metabolic processes. Two specific predictions arise from this: (1) that these processes will produce a wide variety of stable but dysfunctional compounds that increase in concentration with age, and (2) that organisms maintained under conditions that extend lifespan will display a reduced rate of accumulation of such “molecular rubbish”. To test these predictions, novel analytical techniques were developed to investigate the accumulation of damaged compounds in Drosophila melanogaster. Simple preparative techniques were developed to produce digests of whole D. melanogaster for use in three-dimensional (3D) fluorimetry and 1H NMR spectrometry. Cohorts of Drosophila maintained under normal conditions showed an age-related increase in signals consistent with damage whereas those maintained under conditions of low temperature and dietary restriction did not. 1H NMR revealed distinct age-associated spectral changes that will facilitate the identification of novel compounds that both increase and decrease during aging in this species. These findings are consistent with the predictions of the “Green Theory”.
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References
Askelöv P, Korsveldt M, Mannervik B (1976) Error structure of enzyme kinetic experiments, implications for weighting in regression analysis of experimental data. Eur J Biochem 69:61–67
Bass TM, Grandison RC, Wong R, Martinez P, Partridge L, Piper MD (2007) Optimization of dietary restriction protocols in Drosophila. J Gerontol A Biol Sci Med Sci 62(10):1071–1081
Broughton S, Partridge L (2009) Insulin/IGF-like signalling, the central nervous system and aging. Biochem J 418(1):1–12
Buetler TM, Latado H, Baumeyer A, Delatour T (2008) Dicarbonyls stimulate cellular protection systems in primary rat hepatocytes and show anti-inflammatory properties. Ann N Y Acad Sci 1126:113–117
Cai W, He JC, Zhu L, Chen X, Zheng F, Striker GE, Vlassara H (2008) Oral glycotoxins determine the effects of calorie restriction on oxidant stress, age-related diseases, and lifespan. Am J Pathol 173:327–336
Clancy DJ, Kennington WJ (2001) A simple method to achieve consistent larval density in bottle cultures. Dros Inf Serv 84:168–169
Gasser A, Forbes JM (2008) Advanced glycation: Implications in tissue damage and disease. Protein Pept Lett 15:385–391
Doonan R, McElwee JJ, Matthijssens F, Walker GA, Houthoofd K, Back P, Matscheski A, Vanfleteren JR, Gems D (2008) Against the oxidative damage theory of aging: superoxide dismutases protect against oxidative stress but have little or no effect on life span in Caenorhabditis elegans. Genes Dev 22(23):3236–3241
Gems D, McElwee JJ (2005) Broad spectrum detoxification: the major longevity assurance process regulated by insulin/IGF-1 signaling? Mech Age Dev 126:381–387
Gerstbrein B, Stamatas G, Kollias N, Driscoll M (2005) In vivo spectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction in Caenorhabditis elegans. Aging Cell 4:127–137
Grandison RC, Wong R, Bass TM, Partridge L, Piper MD (2009) Effect of a standardised dietary restriction protocol on multiple laboratory strains of Drosophila melanogaster. PLoS ONE 4(1):e4067
Greer EL, Brunet A (2009) Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell 8:113–127. doi:10.1111/j.1474-9726.2009.00459.x
Hofmann T, Ames J, Krome K, Faist V (2001) Determination of the molecular weight distribution of non-enzymatic browning products formed by roasting of glucose and glycine and studies on their effects on NADPH-cytochrome c-reductase and glutathione-S-transferase in Caco-2 cells. Nahrung 45(3):189–194
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 A Biol Sci Med Sci 59:B3–B9
McElwee JJ, Schuster E, Blanc E, Piper MD, Thomas JH, Patel DS, Selman C, Withers DJ, Thornton JM, Partridge L, Gems D (2007) Evolutionary conservation of regulated longevity assurance mechanisms. Genome Biol 8:R132
Miquel J (1971) Ageing of male Drosophila melanogaster: Histological, histochemical and ultrastructural observations. Adv Gerontol Res 3:39–71
Mockett RJ, Bayne AC, Kwong LK, Orr WC, Sohal RS (2003) Ectopic expression of catalase in Drosophila mitochondria increases stress resistance but not longevity. Free Radic Biol Med 34(2):207–217
Monnier VM, Cerami A (1981) Nonenzymatic browning in vivo: possible process for aging of long-lived proteins. Science 211(4481):491–493
Monnier VM, Sell DR (2006) Prevention and repair of protein damage by the Maillard reaction in vivo. Rejuvenation Research 9:264–273
Oudes AJ, Herr CM, Olsen Y, Fleming JE (1998) Age-dependent accumulation of advanced glycation end-products in adult Drosophila melanogaster. Mech Aging Dev 100:221–229
Partridge L, Pletcher SD, Mair W (2005) Dietary restriction, mortality trajectories, risk and damage. Mech Ageing Dev 126(1):35–41
Rabbani N, Thornalley PJ (2008) Dicarbonyls linked to damage in the powerhouse: glycation of mitochondrial proteins and oxidative stress. Biochem Soc Trans 36:1045–1050
Ramsden S, Cheung YY, Seroude L (2008) Functional analysis of the Drosophila immune response during aging. Aging Cell 7(2):225–236
Ritz BW, Gardner EM (2006) Malnutrition and energy restriction differentially affect viral immunity. J Nutr 136:1141–1144
Russell SJ, Kahn CR (2007) Endocrine regulation of ageing. Nature Rev Mol Cell Biol 8:681–691
Sell DR, Biemel KM, Reihl O, Lederer MO, Strauch CM, Monnier VM (2005) Glucosepane is a major protein cross-link of the senescent human extracellular matrix. Relationship with diabetes. J Biol Chem 280:12310–12315
Selman C, Lingard S, Choudhury AI, Batterham RL, Claret M, Clements M, Ramadani F, Okkenhaug K, Schuster E, Blanc E, Piper MD, Al-Qassab H, Speakman JR, Carmignac D, Robinson IC, Thornton JM, Gems D, Partridge L, Withers DJ (2008) Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 22(3):807–818
van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, Slagboom PE, Westendorp RG (2005) Reduced insulin/IGF-1 signalling and human longevity. Aging Cell 4(2):79–85
Wenzel E, Tasto S, Erbersdobler HF, Faist V (2002) Effect of heat-treated proteins on selected parameters of the biotransformation system in the rat. Ann Nutr Metab 46(1):9–16
Acknowledgements
The authors would like to acknowledge the financial support of the Engineering and Physical Sciences Council (EPSRC) and Biological and Biotechnological Sciences Research Council (BBSRC) Strategic Promotion of Aging Research Capacity (SPARC) Programme, the Wellcome Trust and the University of Brighton.
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Iqbal, A., Piper, M., Faragher, R.G.A. et al. Chemical changes in aging Drosophila melanogaster . AGE 31, 343–351 (2009). https://doi.org/10.1007/s11357-009-9105-4
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DOI: https://doi.org/10.1007/s11357-009-9105-4