The Metabolic Profile of Long-Lived Drosophila melanogaster

Abstract

We investigated the age-related changes in the metabolic profile of male Drosophila melanogaster and compared the metabolic profile of flies selected for increased longevity to that of control flies of equal age. We found clear differences in metabolite composition between selection regimes and among age groups. Contrary to results found in a previous study of the transcriptome of these lines the metabolic profile did not show a younger pattern in longevity-selected (LS) flies than in same aged control (C) flies. Rather, many of the metabolites affected by age had levels common to older control individuals in the young LS flies. Furthermore, ageing affected the metabolome in a different LS specific direction. The selection induced difference increased with age. Some metabolites involved in oxidative phosphorylation changed with age highlighting the importance of mitochondrial function in the ageing process. However, these metabolites were not affected by selection for increased longevity, indicating that improvements of mitochondrial function were not involved in the increased lifespan of LS lines. Of the eight metabolites identified as having a significant difference in relative abundance between selection regimes in our study choline, lysine and glucose also show difference among lifespan phenotypes in C. elegans indicating that the correlation between the concentration of these metabolites and longevity was evolutionary conserved. Links between longevity and choline concentration is also found in mice making this metabolite an obvious target for further study.

Preserved cardiac function by vinculin enhances glucose oxidation and extends health- and life-span

“…16 In addition, metabolic profiling of longevity-selected Drosophila established clear differences in steady-state metabolite composition at all ages compared to age-matched controls. 17 This mirrors similar data in C. elegans 18 and mice. 19 Caloric restriction studies in Drosophila 20 and mice 19 provide another link between organismal metabolism and longevity, suggesting not only that caloric restriction causes increased lifespan, but that slowing the changes in the metabolome of flies with age conferred these systemic benefits.…”

“…3(c) and 3(d)], consistent with data suggesting glucose accumulation in longevity selected flies. 17 In addition, we detected significantly increased levels of melezitose with age in VincHE flies [Fig. 3(e)].…”

“…S2(a)], which could influence methionine availability; methionine restriction extends lifespan in mouse, rat, and fly. 32-34 Conversely, additional lysine increases Drosophila longevity, 17 and as longevity selected flies, VincHE flies exhibit increased lysine levels with age [Fig. S2(b)].…”

Sexual dimorphism in the Drosophila melanogaster (Diptera: Drosophilidae) metabolome increases throughout development

“…Drosophila melanogaster has been cited as a particularly useful insect model for metabolomic studies (e.g. Chintapalli et al, 2013), and recent studies have identifi ed many interesting patterns of metabolome variation in this species: for example, variation across the sexes (Hoffmann et al, 2014) and with age (Sarup et al, 2012;Hoffmann et al, 2014), as well as metabolic plasticity to various environmental factors as adults (Overgaard et al, 2007;Colinet et al, 2012;Laye et al, 2015;Williams et al, 2015) and as larvae (Kostal et al, 2011).…”

Proteomics and metabolomics in ageing research: from biomarkers to systems biology

“…The abundances of individual metabolites change with age in several species, including worms [67,68], flies [35,69], mice [70–72], and humans [57,73,74]. In the same vein, differences in abundances of individual metabolites have been associated with long life across multiple species, including work on long-lived mutant worms [75], longevity selected flies [76], calorie restricted and long-lived mutant mice [77], and long-lived human populations [78–80]. Interestingly, fewer studies have attempted to find protein biomarkers of ageing or longevity, and those studies that have been carried out have found mixed results.…”