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

Mason, Janet (2013) The biology of ageing: pro- and anti-ageing signals from the reproductive system. Doctoral thesis, University of East Anglia.

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Abstract

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.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Science > School of Biological Sciences
Depositing User: Mia Reeves
Date Deposited: 06 Mar 2014 11:11
Last Modified: 06 Mar 2014 11:11
URI: https://ueaeprints.uea.ac.uk/id/eprint/47949
DOI:

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