Article

Chemical changes in aging Drosophila melanogaster.

School of Pharmacy and Biomolecular Sciences, University of Brighton, Moulsecoomb, Brighton, UK.
Age (Impact Factor: 3.45). 08/2009; 31(4):343-51. DOI: 10.1007/s11357-009-9105-4
Source: PubMed

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”.

Full-text

Available from: Declan Naughton, Jan 08, 2014
0 Followers
 · 
115 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: In recent years, novel model systems have made significant contributions to our understanding of the processes that control the ageing of whole organisms. However, there are limited data to show that the mechanisms that gerontologists have identified as having a role in organismal ageing contribute significantly to the ageing of the central nervous system. Two recent discoveries illustrate this particularly well. The first is the consistent failure of researchers to demonstrate a simple relationship between organismal ageing and oxidative stress--a mechanism often assumed to have a primary role in brain ageing. The second is the demonstration that senescent cells play a causal part in organismal ageing but remain essentially unstudied in a CNS context. We argue that the animal models now available (including rodents, flies, molluscs and worms), if properly applied, will allow a paradigm shift in our current understanding of the normal processes of brain ageing.
    Nature Reviews Neuroscience 05/2012; 13(6):435-45. DOI:10.1038/nrn3230 · 31.38 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Calorie restriction (CR) is one of the most effective anti-aging interventions in mammals. A modern theory suggests that aging results from a decline in detoxification capabilities and thus accumulation of damaged macromolecules. The present study aimed to determine how short-term CR alters mRNA profiles of genes that encode metabolism and detoxification machinery in liver. Male C57BL/6 mice were fed CR (0, 15, 30, or 40%) diets for one month, followed by mRNA quantification of 98 xenobiotic processing genes (XPGs) in liver, including 7 uptake transporters, 39 phase-I enzymes, 37 phase-II enzymes, 10 efflux transporters, and 5 transcription factors. In general, 15% CR did not alter mRNAs of most XPGs, whereas 30 and 40% CR altered over half of the XPGs (32 increased and 29 decreased). CR up-regulated some phase-I enzymes (fold increase), such as Cyp4a14 (12), Por (2.3), Nqo1 (1.4), Fmo2 (5.4), and Fmo3 (346), and numerous number of phase-II enzymes, such as Sult1a1 (1.2), Sult1d1 (2.0), Sult1e1 (33), Sult3a1 (2.2), Gsta4 (1.3), Gstm2 (1.3), Gstm3 (1.7), and Mgst3 (2.2). CR feminized the mRNA profiles of 32 XPGs in livers of male mice. For instance, CR decreased the male-predominantly expressed Oatp1a1 (97%) and increased the female-predominantly expressed Oatp1a4 (11). In conclusion, short-term CR alters the mRNA levels of over half of the 98 XPGs quantified in livers of male mice, and over half of these alterations appear to be due to feminization of the liver.
    Toxicology and Applied Pharmacology 11/2013; 274(1). DOI:10.1016/j.taap.2013.11.003 · 3.63 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lifespan measurements, also called survival records, are a key phenotype in research on ageing. If external hazards are excluded, ageing alone determines the mortality in a population of model organisms. Understanding the biology of ageing is highly desirable because of the benefits for the wide range of ageing-related diseases. However, it is also extremely challenging because of the underlying complexity. Here, we describe SurvCurv, a new database and online resource focused on model organisms collating survival data for storage and analysis. All data in SurvCurv are manually curated and annotated. The database, available at (www.ebi.ac.uk/thornton-srv/databases/SurvCurv/) offers various functions including plotting, Cox proportional hazards analysis, mathematical mortality models, and statistical tests. It facilitates reanalysis, allows users to analyse their own data and compare it with the largest repository of model-organism data from published experiments, thus, unlocking the potential of survival data and demographics in model organisms. This article is protected by copyright. All rights reserved.
    Aging cell 07/2013; 12(5). DOI:10.1111/acel.12121 · 5.94 Impact Factor