Mair, W.; (2005) Dietary restriction in Drosophila melanogaster. Doctoral thesis , University of London.

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Abstract

Dietary Restriction (DR), the reduction of nutrient intake without malnutrition, was first shown to extend lifespan in rodents in 1935. DR has subsequently proven to be a 'public' method of increasing longevity since its effects are seen in diverse species, ranging from single-celled organisms through to invertebrates and mammals. The appearance of biomarkers of ageing is delayed by DR in non-human primates and indications are that DR may provide health benefits to humans. DR delays the onset of ageing-related pathologies such as cardiovascular disease and cancer, and increases resistance to environmental stresses in rodents. Evolutionary theories of ageing suggest that the effect of DR on longevity represents a trade-off between reproduction and lifespan. In times of famine, an organism's lifetime reproductive success would be increased if reproductive output and the resulting damage were temporarily reduced. Thus, survival to more plentiful times, when reproduction would once again be the most successful strategy, becomes more likely. In this thesis, I investigate the mechanisms by which DR extends lifespan in the model organism Drosophila melanogaster. I use demographic analysis of the effects of applying DR midway though life to show that DR does not slow the rate of ageing but rather removes an acute, transient risk of death that is reversible. I demonstrate that decreased mortality under DR is not the product of lowered mechanical damage resulting from reduced reproductive output. I also show that, unlike the accepted paradigm in mammals, nutrient composition of the food, not calorie intake, is the key detenninant of lifespan extension via DR in Drosophila. DR flies are shown to be resistant to starvation, which may be indicative of the mechanisms through which DR extends life. However, DR flies are not globally resistant to other environmental stresses including thermal stress, in contrast to DR rodents that have increased thermotolerance. Together, these data give insight into the effects of DR in Drosophila and provide a framework for determining the acute risk of death posed by high nutrient intake. They also provide future directions for work in mammalian systems that will enable us to better understand if the mechanisms by which DR extends life really are conserved across species, or whether they are examples of convergent evolution.

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