Abstract
Exogenously added lithocholic bile acid and some other bile acids slow down yeast chronological aging by eliciting a hormetic stress response and altering mitochondrial functionality. Unlike animals, yeast cells do not synthesize bile acids. We therefore hypothesized that bile acids released into an ecosystem by animals may act as interspecies chemical signals that generate selective pressure for the evolution of longevity regulation mechanisms in yeast within this ecosystem. To empirically verify our hypothesis, in this study we carried out a three-step process for the selection of long-lived yeast species by a long-term exposure to exogenous lithocholic bile acid. Such experimental evolution yielded 20 long-lived mutants, three of which were capable of sustaining their considerably prolonged chronological lifespans after numerous passages in medium without lithocholic acid. The extended longevity of each of the three long-lived yeast species was a dominant polygenic trait caused by mutations in more than two nuclear genes. Each of the three mutants displayed considerable alterations to the age-related chronology of mitochondrial respiration and showed enhanced resistance to chronic oxidative, thermal, and osmotic stresses. Our findings empirically validate the hypothesis suggesting that hormetic selective forces can drive the evolution of longevity regulation mechanisms within an ecosystem.
Highlights
We have identified lithocholic acid (LCA), a bile acid, as a potent geroprotector that delays chronological aging in the yeast Saccharomyces cerevisiae (Goldberg et al, 2010b)
We provide evidence that the extended longevity of each of the three long-lived yeast mutants is a dominant polygenic trait caused by mutations in more than two nuclear genes
To empirically verify our hypothesis suggesting that hormetic selective forces can drive the evolution of longevity regulation mechanisms within ecosystems, we carried out a three-step selection of long-lived yeast species by a lasting exposure to LCA under laboratory conditions
Summary
We have identified lithocholic acid (LCA), a bile acid, as a potent geroprotector that delays chronological aging in the yeast Saccharomyces cerevisiae (Goldberg et al, 2010b). Bile acids extend healthy lifespan in animals because they act as signaling molecules that enable to sustain lipid, glucose, and energy homeostasis (Motola et al, 2006; Gerisch et al, 2007; Russell and Kahn, 2007; Ramalho et al, 2008; Thomas et al, 2008; Amaral et al, 2009; Hylemon et al, 2009; Lefebvre et al, 2009; Monte et al, 2009; Tiwari and Maiti, 2009; Vallim and Edwards, 2009; Goldberg et al, 2011, 2013; Pols et al, 2011; Wollam et al, 2011, 2012; Lee and Schroeder, 2012; Chiang, 2013; de Aguiar Vallim et al, 2013; Groen and Kuipers, 2013; Li and Chiang, 2013; Magner et al, 2013; Arlia-Ciommo et al, 2014b; Mahanti et al, 2014). Bile acids extend healthy lifespan in animals because these mildly toxic molecules with detergent-like properties can activate detoxification of xenobiotics, promoting chemical hormesis and operating as endobiotic regulators of aging that improve health and prolong longevity (Amador-Noguez et al, 2004, 2007; Gems, 2007; Russell and Kahn, 2007; Gems and Partridge, 2008; Burstein et al, 2012a; Arlia-Ciommo et al, 2014b; Li and Chiang, 2014; Medkour and Titorenko, 2016)
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