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

Autor: Laye MJ; Buck Institute for Research on Aging, Novato, CA, USA., Tran V; Division of Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; Department of Medicine, Clinical Biomarkers Laboratory, Emory University, Atlanta, GA, USA., Jones DP; Division of Pulmonary Allergy & Critical Care Medicine, Department of Medicine, Emory University, Atlanta, GA, USA.; Department of Medicine, Clinical Biomarkers Laboratory, Emory University, Atlanta, GA, USA., Kapahi P; Buck Institute for Research on Aging, Novato, CA, USA., Promislow DE; Department of Pathology, University of Washington, Seattle, WA, USA.; Department of Biology, University of Washington, Seattle, WA, USA.
Jazyk: angličtina
Zdroj: Aging cell [Aging Cell] 2015 Oct; Vol. 14 (5), pp. 797-808. Date of Electronic Publication: 2015 Jun 18.
DOI: 10.1111/acel.12358
Abstrakt: 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.
(© 2015 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.)
Databáze: MEDLINE
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