Year: 2013
Type: dissertation
Abstract: \nThis context of this thesis is that ageing is characterised by the accumulation of random cellular \ndamage leading to a decrease in reproductive function and survival, which ends in death. The \nantagonistic pleiotropy theory for ageing suggests selection favours genes with positive effects on \nearly life even if detrimental effects are observed in later life, indicating a trade-off between lifespan \nand reproductive output. Ageing, however, is a complex genetic trait and strong interactions \nbetween genes that influence longevity and environment including with diet, stress and \npharmacological factors have been discovered. Consistent with this, recent work has shown that \nboth genetic and dietary alterations can substantially increase the healthy lifespan of a range of \norganisms, across many taxa. \nThe research in this thesis aims to examine whether a major cellular protection mechanism, \nautophagy, can counteract the lifespan-reducing effects of reproduction in the model organism \nDrosophila melanogaster. Experiments were conducted on males and females with different \nreproductive and nutritional status. Effects of genetic and pharmacological activators of autophagy \non lifespan and reproductive success were investigated, as were trade-offs between reproduction \nand survival. The pharmacological autophagy activator Torin1, when added to the diet extended \nsurvival. There was no evidence of a trade-off of extended lifespan with reduced fertility, indicating \ntheses are controlled, at least in part, independently. Hence, lifespan extension was apparently cost \nfree suggesting Torin1 may offer a potentially fruitful route for further studies of healthy lifespan \nextension. Autophagy gene 8 (Atg8a) overexpression and knockdown manipulations were used to \ndetermine effects of autophagy up- and down-regulation on lifespan and reproductive success. \nNeither manipulation had the predicted effect on lifespan, although Atg8a knockdown did \ncompromise, to some extent, the survival response of females to diet restriction. In the final piece \nof research in the thesis, diet-deprived males lost the ability to respond adaptively to rivals. This \neffect was not protein-specific so is predicted to be autophagy independent.
Author: Janet Mason
Language: English
Subfield: Aging
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W1657763970