The effects of age and dietary restriction on the tissue‐specific metabolome of Drosophila

Abstract

Dietary restriction (DR) is a robust intervention that extends lifespan and slows the onset of age-related diseases in diverse organisms. While significant progress has been made in attempts to uncover the genetic mechanisms of DR, there are few studies on the effects of DR on the metabolome. In recent years, metabolomic profiling has emerged as a powerful technology to understand the molecular causes and consequences of natural aging and disease-associated phenotypes. Here, we use high-resolution mass spectroscopy and novel computational approaches to examine changes in the metabolome from the head, thorax, abdomen, and whole body at multiple ages in Drosophila fed either a nutrient-rich ad libitum (AL) or nutrient-restricted (DR) diet. Multivariate analysis clearly separates the metabolome by diet in different tissues and different ages. DR significantly altered the metabolome and, in particular, slowed age-related changes in the metabolome. Interestingly, we observed interacting metabolites whose correlation coefficients, but not mean levels, differed significantly between AL and DR. The number and magnitude of positively correlated metabolites was greater under a DR diet. Furthermore, there was a decrease in positive metabolite correlations as flies aged on an AL diet. Conversely, DR enhanced these correlations with age. Metabolic set enrichment analysis identified several known (e.g., amino acid and NAD metabolism) and novel metabolic pathways that may affect how DR effects aging. Our results suggest that network structure of metabolites is altered upon DR and may play an important role in preventing the decline of homeostasis with age.

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

“…Colinet et al, 2012;Hoffmann et al, 2014;Laye et al, 2015;Williams et al, 2015). In this study, we found clear variation in metabolic profi le across larval, pupal and adult developmental stages, as well as sex differences in the overall profi le that appear to increase throughout development.…”

“…Colinet et al, 2012) but far fewer than some other research (e.g. Laye et al, 2015), which may refl ect our specifi c need to optimise the gas chromatography process for sample types from different holometabolous stages. Of these compounds, 14 were present in both sexes and all stages.…”

“…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).…”

Tissue-specific down-regulation of S-adenosyl-homocysteine via suppression of dAhcyL1/dAhcyL2 extends health span and life span in Drosophila

“…Similarly, studies in worms (Fuchs et al 2010), mice (Tomas-Loba et al 2013), and humans (Yu et al 2012) have documented changes in the metabolome during the aging process. Recently, untargeted metabolomics analysis in flies (Hoffman et al 2014) has suggested that DR might reverse age-dependent metabolic reprogramming at the tissue (Laye et al 2015) and whole-organism (Avanesov et al 2014) levels. Despite these studies, the mechanisms underlying age-dependent metabolic reprogramming, the nature of the metabolites that change with time, and their effect on life span are still poorly characterized.…”

Pengehadan Kalori, Fungsi Kognitif dan Penuaan: Peranan terhadap Sistem Biologi

“…Tempoh berpuasa juga telah terbukti mempunyai kesan antimutagenik, antibakteria dan antikarsinogenik (Lee & Longo 2011). Kesan pengehadan kalori juga mempengaruhi metabolit di dalam tubuh terutama dalam metabolom hepar (Laye et al 2015;Jové et al 2014). Namun demikian, kebanyakan kajian dijalankan melibatkan spesies haiwan dan kurang kajian dijalankan ke atas manusia.…”