  The fruit fly D. melanogaster is increasingly used as a model organism for
studying acute hypoxia tolerance and for studying aging, but the interactions
between these two factors are not well known. Here we show that hypoxia
tolerance degrades with age in post-hypoxic recovery of whole-body movement,
heart rate and ATP content. We previously used 1H NMR metabolomics and a
constraint-based model of ATP-generating metabolism to discover the end
products of hypoxic metabolism in flies and generate hypotheses for the
biological mechanisms. We expand the reactions in the model using tissue- and
age-specific microarray data from the literature, and then examine metabolomic
profiles of thoraxes after 4 hours at 0.5% O2 and after 5 minutes of recovery
in 40- versus 3-day-old flies. Model simulations were constrained to fluxes
calculated from these data. Simulations suggest that the decreased ATP
production during reoxygenation seen in aging flies can be attributed to
reduced recovery of mitochondrial respiration pathways and concomitant
over-dependence on the acetate production pathway as an energy source.
