Palmer, Daniel and Clancy, David and Shirras, Alan (2018) Direct selection on lifespan in Drosophila Melanogaster to elucidate the mechanisms of longevity. PhD thesis, Lancaster University.
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Abstract
Artificial selection can be used to create model organisms tailored for a specific research question. Selection experiments using Drosophila have been a prominent aspect of ageing research over the last 40 years, being used to elucidate the evolutionary roots of ageing, as well as the mechanisms and corollaries by which lifespan extension is achieved in semi-natural populations. With the advent of modern sequencing, and other -omics, technologies, selection experiments offer an exciting opportunity to investigate the molecular and genetic mechanisms of longevity. We selected directly on lifespan in a recently wild-caught population of Drosophila melanogaster, achieving a median lifespan extension effect of 30% and a delay in the onset of ageing of 68% after 5 generations of selection. Various life-history traits and stress responses were measured and one line from each the selected and control regimes were analysed using RNA-Seq. Changes in stress resistances were observed in the selected flies, with the long-lived lines showing an increase in starvation resistance and a decrease in heat stress resistance, both responses being consistent with previous selection experiments. Desiccation resistance was initially increased by selection, but this declined after 5 generations of selection, suggesting that it was not necessary for the long-lived phenotype. Likewise, and somewhat unexpectedly, oxidative stress resistance was not altered in the selected lines, and neither did levels of protein carbonylation change, suggesting that early life prevention of oxidative damage is not an indicator of lifespan. Differential expression analysis of the long-lived flies revealed enrichment of developmental and metabolic biological processes amongst the genes with the highest fold-change. These categories are commonly altered in long-lived expression profiles and suggest the longevity of the selected lines may be due to alterations in developmental pathways in accordance with the hyperfunction theory of ageing.