Chemical changes in aging Drosophila melanogaster

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 1 H 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. 1 H 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".

Short-term calorie restriction feminizes the mRNA profiles of drug metabolizing enzymes and transporters in livers of mice

“…The up-regulation of phase-I and phase-II metabolizing genes, which renders broad spectrum detoxification, is proposed to be a longevity assurance mechanism. This theory was raised upon the findings in long-lived mutants of C. elegans (McElwee et al, 2004), and is supported by accumulating evidence in Drosophila (Iqbal et al, 2009) and rodents (Amador-Noguez et al, 2007; Steinbaugh et al, 2012). In alignment with this hypothesis, decreased mRNA expression of many genes in xenobiotic metabolism pathways was reported in livers of aged mice (Cao et al, 2001; Lee et al, 2011; Fu et al, 2012).…”

Unlocking the potential of survival data for model organisms through a new database and online analysis platform:SurvCurv

“…The maximum Drosophila lifespan recorded in SurvCurv is 147 days {a female fly of the Dahomey strain kept at 18 °C [Iqbal et al . ( 2009 ), SurvCurv ID: 204]}, and the maximum recorded for C. elegans is 53 days {rrf-3(pk1426) daf-2 and smg-1 RNAi [Masse et al . ( 2008 ), SurvCurv ID: 892]}.…”

“…The maximum change in median lifespan between control and treatment in Drosophila is 67 days, or 110%, for a change in temperature from 25 to 18 °C [Iqbal et al . ( 2009 ), SurvCurv IDs: 202 and 204] and the second largest change is 26.5 days, corresponding to a 53% increase, for a homozygote knock-out of Drosophila insulin-like peptides 2-3,5 [Grönke et al . ( 2010 ), SurvCurv IDs: 427 and 426].…”