The biology of ageing: pro- and anti-ageing signals from the reproductive system

Abstract This context of this thesis is that ageing is characterised by the accumulation of random cellular damage leading to a decrease in reproductive function and survival, which ends in death. The antagonistic pleiotropy theory for ageing suggests selection favours genes with positive effects on early life even if detrimental effects are observed in later life, indicating a trade-off between lifespan and reproductive output. Ageing, however, is a complex genetic trait and strong interactions between genes that influence longevity and environment including with diet, stress and pharmacological factors have been discovered. Consistent with this, recent work has shown that both genetic and dietary alterations can substantially increase the healthy lifespan of a range of organisms, across many taxa. The research in this thesis aims to examine whether a major cellular protection mechanism, autophagy, can counteract the lifespan-reducing effects of reproduction in the model organism Drosophila melanogaster. Experiments were conducted on males and females with different reproductive and nutritional status. Effects of genetic and pharmacological activators of autophagy on lifespan and reproductive success were investigated, as were trade-offs between reproduction and survival. The pharmacological autophagy activator Torin1, when added to the diet extended survival. There was no evidence of a trade-off of extended lifespan with reduced fertility, indicating theses are controlled, at least in part, independently. Hence, lifespan extension was apparently cost free suggesting Torin1 may offer a potentially fruitful route for further studies of healthy lifespan extension. Autophagy gene 8 (Atg8a) overexpression and knockdown manipulations were used to determine effects of autophagy up- and down-regulation on lifespan and reproductive success. Neither manipulation had the predicted effect on lifespan, although Atg8a knockdown did compromise, to some extent, the survival response of females to diet restriction. In the final piece of research in the thesis, diet-deprived males lost the ability to respond adaptively to rivals. This effect was not protein-specific so is predicted to be autophagy independent.

Name dc:type.qualificationname

phd

Level dc:type.qualificationlevel

doctoral

Grantor dc:publisher.institution

University of East Anglia

Year dc:date.issued

2013

Author dc:creator

• Mason, Janet

Language dc:language

en