Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

Lutchman, Vicky; Medkour, Younes; Samson, Eugenie; Arlia-Ciommo, Anthony; Dakik, Pamela; Cortes, Berly; Feldman, Rachel; Mohtashami, Sadaf; McAuley, Mélissa; Chancharoen, Marisa; Rukundo, Belise; Simard, Éric; Titorenko, Vladimir I.

doi:10.18632/oncotarget.7665

Cited by 25 publications

(58 citation statements)

References 117 publications

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“…This network of signaling pathways and protein kinases coordinates certain longevity-defining cellular processes, including stress responses, protein synthesis in the cytosol and mitochondria, maintenance of nuclear and mitochondrial genomes, autophagy, mitochondrial respiration, peroxisome biogenesis, gluconeogenesis, lipid metabolism, glyoxylate cycle, glycogen synthesis and degradation, and the synthesis of amino acids and fatty acids [1, 6, 11, 27–32, 59, 61–73] (Figure 1). Information flow along this network in yeast is controlled by such aging-delaying chemical compounds as resveratrol, rapamycin, caffeine, spermidine, myriocin, methionine sulfoxide, lithocholic acid and cryptotanshinone [3, 5, 6, 8–10, 12, 14, 43, 54, 74–78]. …”

Section: Introductionmentioning

confidence: 99%

“…We have recently discovered six plant extracts (PEs) that increase yeast chronological lifespan (CLS) to a greater extent than any of the presently known longevity-extending chemical compounds [78]. We demonstrated that each of these PEs (which we call PE4, PE5, PE6, PE8, PE12 and PE21) decelerates chronological aging and has different effects on certain longevity-defining cellular processes [78].…”

Section: Introductionmentioning

confidence: 99%

“…We demonstrated that each of these PEs (which we call PE4, PE5, PE6, PE8, PE12 and PE21) decelerates chronological aging and has different effects on certain longevity-defining cellular processes [78]. In this study, we investigated how a mutational impairment of each of the signaling pathways and protein kinases comprising the longevity-defining network influences the aging-delaying efficiencies of PE4, PE5, PE6, PE8, PE12 and PE21.…”

Section: Introductionmentioning

confidence: 99%

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Six plant extracts delay yeast chronological aging through different signaling pathways

et al. 2016

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Our recent study has revealed six plant extracts that slow yeast chronological aging more efficiently than any chemical compound yet described. The rate of aging in yeast is controlled by an evolutionarily conserved network of integrated signaling pathways and protein kinases. Here, we assessed how single-gene-deletion mutations eliminating each of these pathways and kinases affect the aging-delaying efficiencies of the six plant extracts. Our findings imply that these extracts slow aging in the following ways: 1) plant extract 4 decreases the efficiency with which the pro-aging TORC1 pathway inhibits the anti-aging SNF1 pathway; 2) plant extract 5 mitigates two different branches of the pro-aging PKA pathway; 3) plant extract 6 coordinates processes that are not assimilated into the network of presently known signaling pathways/protein kinases; 4) plant extract 8 diminishes the inhibitory action of PKA on SNF1; 5) plant extract 12 intensifies the anti-aging protein kinase Rim15; and 6) plant extract 21 inhibits a form of the pro-aging protein kinase Sch9 that is activated by the pro-aging PKH1/2 pathway.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Six plant extracts delay yeast chronological aging through different signaling pathways

et al. 2016

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“…This response consists in the ability of yeast to develop mechanisms of protection against cellular damage caused by the mildly toxic molecules of bile acids (Goldberg et al, 2010a,b; Burstein et al, 2012a). Of note, our analysis of how different concentrations of LCA impact yeast longevity has revealed that this bile acid delays yeast chronological aging by eliciting a hormetic stress response (Goldberg et al, 2010b; Burstein et al, 2012a), which is characterized by a non-linear and biphasic dose–response curve (Goldberg et al, 2010a; Calabrese and Mattson, 2011; Burstein et al, 2012a; Calabrese et al, 2012; Leonov et al, 2015; Lutchman et al, 2016). Our recent studies also demonstrated that the ability of LCA to elicit such longevity-extending stress response is due in part to alterations in mitochondrial functionality caused by LCA, including changes in the age-related chronology of mitochondrial respiration (Goldberg et al, 2010b; Burstein et al, 2012b; Beach et al, 2013, 2015a,b; Arlia-Ciommo et al, 2014a,b; Burstein and Titorenko, 2014; Medkour and Titorenko, 2016).…”

Section: Resultsmentioning

confidence: 99%

Empirical Validation of a Hypothesis of the Hormetic Selective Forces Driving the Evolution of Longevity Regulation Mechanisms

et al. 2016

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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.

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“…Akin to cell susceptibili-ty to apoptotic and liponecrotic forms of cell death, such resistance to acute stresses is one of the key traits of early-life fitness [12, 48, 58, 61, 65, 99, 100, 104 - 109]. …”

Section: Resultsmentioning

confidence: 99%

Empirical verification of evolutionary theories of aging

Kyryakov

Gomez-Perez

Glebov

et al. 2016

Aging

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We recently selected 3 long-lived mutant strains of Saccharomyces cerevisiae by a lasting exposure to exogenous lithocholic acid. Each mutant strain can maintain the extended chronological lifespan after numerous passages in medium without lithocholic acid. In this study, we used these long-lived yeast mutants for empirical verification of evolutionary theories of aging. We provide evidence that the dominant polygenic trait extending longevity of each of these mutants 1) does not affect such key features of early-life fitness as the exponential growth rate, efficacy of post-exponential growth and fecundity; and 2) enhances such features of early-life fitness as susceptibility to chronic exogenous stresses, and the resistance to apoptotic and liponecrotic forms of programmed cell death. These findings validate evolutionary theories of programmed aging. We also demonstrate that under laboratory conditions that imitate the process of natural selection within an ecosystem, each of these long-lived mutant strains is forced out of the ecosystem by the parental wild-type strain exhibiting shorter lifespan. We therefore concluded that yeast cells have evolved some mechanisms for limiting their lifespan upon reaching a certain chronological age. These mechanisms drive the evolution of yeast longevity towards maintaining a finite yeast chronological lifespan within ecosystems.

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Discovery of plant extracts that greatly delay yeast chronological aging and have different effects on longevity-defining cellular processes

Cited by 25 publications

References 117 publications

Six plant extracts delay yeast chronological aging through different signaling pathways

Six plant extracts delay yeast chronological aging through different signaling pathways

Empirical Validation of a Hypothesis of the Hormetic Selective Forces Driving the Evolution of Longevity Regulation Mechanisms

Empirical verification of evolutionary theories of aging

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