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Empirical Testing of the Evolutionary Theories of Aging Using Laboratory-Evolved Yeast Mutants with Extended Lifespan

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Empirical Testing of the Evolutionary Theories of Aging Using Laboratory-Evolved Yeast Mutants with Extended Lifespan

Gomez-Perez, Alejandra (2013) Empirical Testing of the Evolutionary Theories of Aging Using Laboratory-Evolved Yeast Mutants with Extended Lifespan. Masters thesis, Concordia University.

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Abstract

We recently conducted a multistep selection of long-lived yeast mutants by a lasting exposure to lithocholic acid, a longevity-extending natural compound. Three selected long-lived mutant strains, called 3, 5 and 12, were able to maintain their extended lifespans following numerous passages in medium lacking lithocholic acid. In studies described in this thesis I demonstrated that the greatly extended longevity of each of the three long-lived yeast mutants evolved under laboratory conditions is a dominant polygenic trait caused by mutations in more than two genes. To empirically validate evolutionary theories of programmed or non-programmed aging and age-related death, I investigated if the dominant mutations that extend longevity of each of the three long-lived yeast mutants evolved under laboratory conditions influence early-life fitness when each of these mutants grows and ages alone, in the absence of a parental wild-type yeast strain that does not carry longevity-extending mutations. My studies revealed that these mutations (1) do not affect such key traits of early-life fitness as the exponential growth rate, efficacy of post-exponential growth and fecundity of yeast cells; and (2) enhance such key traits of early-life fitness as cell susceptibility to chronic exogenous stresses, mitochondria-controlled apoptosis triggered by a brief exposure to exogenous hydrogen peroxide, and lipoptotic form of death triggered by a short-term exposure to exogenous palmitoleic acid. These findings provide irrefutable proof of evolutionary theories of aging based on the concept of programmed aging and age-related death and invalidate evolutionary theories of non-programmed aging and age-related death. I then examined if the dominant mutations that extend longevity of each of the three long-lived yeast mutants evolved under laboratory conditions influence the relative fitness of each of these mutants in a direct competition assay with a parental wild-type strain. This assay mimics under various laboratory conditions the process of natural selection within a mixed population of yeast cells that (1) exhibit different longevity-defining genetic backgrounds; (2) differ in their lifespans if grow as a genetically homogenous cell population; and (3) compete for nutrients and other environmental resources. I found that in a population of mixed cells grown on 1% ethanol the dominant mutations that extend longevity of the three long-lived yeast mutants 3, 5 and 12 reduce the relative fitness of each of them in a direct competition assay with a parental wild-type strain. Based on these findings, I concluded that under laboratory conditions mimicking the process of natural selection within an ecosystem composed of yeast cells having different longevity-defining genetic backgrounds, each of the three long-lived mutants is forced out of the ecosystem by a parental wild-type strain exhibiting shorter lifespan. My findings imply that (1) yeast cells have evolved some mechanisms for limiting their lifespan upon reaching a certain chronological age; and (2) these mechanisms drive the evolution of yeast longevity towards maintaining a finite yeast lifespan within ecosystems. I hypothesize that these mechanisms may consist in the ability of a parental wild-type strain to secrete into an ecosystem certain compounds (small molecules and/or proteins) that slow down growth and/or kill long-lived yeast mutants within this ecosystem.

Divisions:Concordia University > Faculty of Arts and Science > Biology
Item Type:Thesis (Masters)
Authors:Gomez-Perez, Alejandra
Institution:Concordia University
Degree Name:M. Sc.
Program:Biology
Date:August 2013
Thesis Supervisor(s):Titorenko, Vladimir
ID Code:977602
Deposited By: ALEJANDRA GOMEZ PEREZ
Deposited On:26 Nov 2013 15:50
Last Modified:18 Jan 2018 17:44
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