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  1. Article: Yeast at the Forefront of Research on Ageing and Age-Related Diseases.

    Sampaio-Marques, Belém / Burhans, William C / Ludovico, Paula

    Progress in molecular and subcellular biology

    2019  Volume 58, Page(s) 217–242

    Abstract: Ageing is a complex and multifactorial process driven by genetic, environmental and stochastic factors that lead to the progressive decline of biological systems. Mechanisms of ageing have been extensively investigated in various model organisms and ... ...

    Abstract Ageing is a complex and multifactorial process driven by genetic, environmental and stochastic factors that lead to the progressive decline of biological systems. Mechanisms of ageing have been extensively investigated in various model organisms and systems generating fundamental advances. Notably, studies on yeast ageing models have made numerous and relevant contributions to the progress in the field. Different longevity factors and pathways identified in yeast have then been shown to regulate molecular ageing in invertebrate and mammalian models. Currently the best candidates for anti-ageing drugs such as spermidine and resveratrol or anti-ageing interventions such as caloric restriction were first identified and explored in yeast. Yeasts have also been instrumental as models to study the cellular and molecular effects of proteins associated with age-related diseases such as Parkinson's, Huntington's or Alzheimer's diseases. In this chapter, a review of the advances on ageing and age-related diseases research in yeast models will be made. Particular focus will be placed on key longevity factors, ageing hallmarks and interventions that slow ageing, both yeast-specific and those that seem to be conserved in multicellular organisms. Their impact on the pathogenesis of age-related diseases will be also discussed.
    MeSH term(s) Aging/drug effects ; Aging/genetics ; Aging/physiology ; Animals ; Caloric Restriction ; Humans ; Longevity/drug effects ; Longevity/genetics ; Longevity/physiology ; Models, Biological ; Neurodegenerative Diseases/genetics ; Neurodegenerative Diseases/pathology ; Neurodegenerative Diseases/physiopathology ; Rejuvenation/physiology ; Saccharomyces cerevisiae/cytology ; Saccharomyces cerevisiae/drug effects ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae/physiology
    Language English
    Publishing date 2019-03-25
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 0079-6484
    ISSN 0079-6484
    DOI 10.1007/978-3-030-13035-0_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article: Reactive oxygen species, ageing and the hormesis police

    Ludovico, Paula / Burhans, William C

    FEMS yeast research. 2014 Feb., v. 14, no. 1

    2014  

    Abstract: For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations ...

    Abstract For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations are related to the recent discovery that caloric restriction and other experimental manipulations promote longevity by inducing hormesis effects in association with increased reactive oxygen species (ROS). The beneficial role of ROS in lifespan extension is consistent with the essential role of these molecules in cell signalling. However, the identity of specific forms of ROS that promote longevity remains unclear. In this article, we argue that in several model systems, hydrogen peroxide plays a crucial role in the induction of hormesis.
    Keywords cell communication ; hormesis ; hydrogen peroxide ; longevity ; low calorie diet ; models ; senescence ; yeasts
    Language English
    Dates of publication 2014-02
    Size p. 33-39.
    Publishing place Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies
    Document type Article
    ZDB-ID 2036775-2
    ISSN 1567-1364 ; 1567-1356
    ISSN (online) 1567-1364
    ISSN 1567-1356
    DOI 10.1111/1567-1364.12070
    Database NAL-Catalogue (AGRICOLA)

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  3. Article ; Online: Reactive oxygen species, ageing and the hormesis police.

    Ludovico, Paula / Burhans, William C

    FEMS yeast research

    2013  Volume 14, Issue 1, Page(s) 33–39

    Abstract: For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations ...

    Abstract For more than 50 years, the free radical theory served as the paradigm guiding most investigations of ageing. However, recent studies in a variety of organisms have identified conceptual and practical limitations to this theory. Some of these limitations are related to the recent discovery that caloric restriction and other experimental manipulations promote longevity by inducing hormesis effects in association with increased reactive oxygen species (ROS). The beneficial role of ROS in lifespan extension is consistent with the essential role of these molecules in cell signalling. However, the identity of specific forms of ROS that promote longevity remains unclear. In this article, we argue that in several model systems, hydrogen peroxide plays a crucial role in the induction of hormesis.
    MeSH term(s) Animals ; Cell Survival ; Hormesis ; Humans ; Longevity ; Models, Biological ; Reactive Oxygen Species/metabolism ; Reactive Oxygen Species/toxicity
    Chemical Substances Reactive Oxygen Species
    Language English
    Publishing date 2013-09-09
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 2036775-2
    ISSN 1567-1364 ; 1567-1356
    ISSN (online) 1567-1364
    ISSN 1567-1356
    DOI 10.1111/1567-1364.12070
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article: DNA damage and DNA replication stress in yeast models of aging.

    Burhans, William C / Weinberger, Martin

    Sub-cellular biochemistry

    2012  Volume 57, Page(s) 187–206

    Abstract: DNA damage DNA damage is an important factor in aging in all eukaryotes. Although connections between DNA damage DNA damage and aging have been extensively investigated in complex organisms, only a relatively few studies have investigated DNA damage DNA ... ...

    Abstract DNA damage DNA damage is an important factor in aging in all eukaryotes. Although connections between DNA damage DNA damage and aging have been extensively investigated in complex organisms, only a relatively few studies have investigated DNA damage DNA damage as an aging factor in the model organism S. cerevisiae. Several of these studies point to DNA replication stress DNA replication stress as a cause of age-dependent DNA damage DNA damage in the replicative model of aging, which measures how many times budding yeast cells divide before they senesce and die. Even fewer studies have investigated how DNA damage DNA damage contributes to aging in the chronological aging chronological aging model, which measures how long cells in stationary phase cultures retain reproductive capacity. DNA replication stress DNA replication stress also has been implicated as a factor in chronological aging chronological aging . Since cells in stationary phase are generally considered to be "post-mitotic" and to reside in a quiescent G0/G1 state, the notion that defects in DNA replication might contribute to chronological aging chronological aging appears to be somewhat paradoxical. However, the results of recent studies suggest that a significant fraction of cells in stationary phase cultures are not quiescent, especially in experiments that employ defined medium, which is frequently employed to assess chronological lifespan. Most cells that fail to achieve quiescence remain in a viable, but non-dividing state until they eventually die, similar to the senescent state in mammalian cells. In this chapter we discuss the role of DNA damage DNA damage and DNA replication stress DNA replication stress in both replicative and chronological aging chronological aging in S. cerevisiae. We also discuss the relevance of these findings to the emerging view that DNA damage DNA damage and DNA replication stress DNA replication stress are important components of the senescent state that occurs at early stages of cancer.
    MeSH term(s) Aging/genetics ; Aging/metabolism ; Animals ; Cell Division ; DNA Damage ; DNA Replication ; DNA, Fungal/biosynthesis ; Gene Expression Regulation, Fungal ; Gene Expression Regulation, Neoplastic ; Humans ; Longevity ; Models, Genetic ; Neoplasms/genetics ; Neoplasms/metabolism ; Saccharomycetales/genetics ; Saccharomycetales/growth & development ; Saccharomycetales/metabolism ; Stress, Physiological/genetics ; Time Factors
    Chemical Substances DNA, Fungal
    Language English
    Publishing date 2012
    Publishing country United States
    Document type Journal Article ; Review
    ISSN 0306-0225 ; 0096-8757
    ISSN 0306-0225 ; 0096-8757
    DOI 10.1007/978-94-007-2561-4_9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article: Longevity pathways and maintenance of the proteome: the role of autophagy and mitophagy during yeast ageing.

    Sampaio-Marques, Belém / Burhans, William C / Ludovico, Paula

    Microbial cell (Graz, Austria)

    2014  Volume 1, Issue 4, Page(s) 118–127

    Abstract: Ageing is a complex and multi-factorial process that results in the progressive accumulation of molecular alterations that disrupt different cellular functions. The budding ... ...

    Abstract Ageing is a complex and multi-factorial process that results in the progressive accumulation of molecular alterations that disrupt different cellular functions. The budding yeast
    Language English
    Publishing date 2014-04-07
    Publishing country Austria
    Document type Journal Article ; Review
    ZDB-ID 2814756-X
    ISSN 2311-2638
    ISSN 2311-2638
    DOI 10.15698/mic2014.04.136
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article ; Online: Revisiting the free radical theory using next-generation sequencing technology.

    Burhans, William C / Weinberger, Martin

    Aging

    2010  Volume 2, Issue 8, Page(s) 459–460

    MeSH term(s) Aging/physiology ; Animals ; Benzene Derivatives/toxicity ; Cellular Senescence/genetics ; Cellular Senescence/physiology ; Free Radicals/toxicity ; Humans ; Longevity ; Mutagenesis ; Oxidative Stress/genetics ; Peroxidases/genetics ; Peroxidases/metabolism ; Phenotype ; Polymorphism, Genetic ; Saccharomyces cerevisiae Proteins/genetics ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Analysis, DNA ; Yeasts/drug effects ; Yeasts/physiology
    Chemical Substances Benzene Derivatives ; Free Radicals ; Saccharomyces cerevisiae Proteins ; Peroxidases (EC 1.11.1.-) ; Tsa1 protein, S cerevisiae (EC 1.11.1.-) ; cumene hydroperoxide (PG7JD54X4I)
    Language English
    Publishing date 2010-08-17
    Publishing country United States
    Document type Journal Article ; Comment
    ISSN 1945-4589
    ISSN (online) 1945-4589
    DOI 10.18632/aging.100188
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Histone genes, DNA replication, apoptosis and aging: what are the connections?

    Burhans, William C / Weinberger, Martin

    Cell cycle (Georgetown, Tex.)

    2010  Volume 9, Issue 20, Page(s) 4047–4048

    MeSH term(s) Aging/genetics ; Apoptosis/genetics ; DNA Replication ; Fungal Proteins/genetics ; Fungal Proteins/metabolism ; Histones/genetics ; Hydroxyurea/metabolism ; Nucleic Acid Synthesis Inhibitors/metabolism ; Saccharomyces cerevisiae/cytology ; Saccharomyces cerevisiae/genetics
    Chemical Substances Fungal Proteins ; Histones ; Nucleic Acid Synthesis Inhibitors ; Hydroxyurea (X6Q56QN5QC)
    Language English
    Publishing date 2010-10-13
    Publishing country United States
    Document type Comment ; Journal Article
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Histone genes, DNA replication, apoptosis and aging: What are the connections?

    Burhans, William C / Weinberger, Martin

    Cell cycle (Georgetown, Tex.)

    2010  Volume 9, Issue 20, Page(s) 4047–4048

    Language English
    Publishing date 2010-10-15
    Publishing country United States
    Document type Journal Article
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.9.20.13524
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: The cell cycle is a redox cycle: linking phase-specific targets to cell fate.

    Burhans, William C / Heintz, Nicholas H

    Free radical biology & medicine

    2009  Volume 47, Issue 9, Page(s) 1282–1293

    Abstract: Reactive oxygen species (ROS) regulate the strength and duration of signaling through redox-dependent signal transduction pathways via the cyclic oxidation/reduction of cysteine residues in kinases, phosphatases, and other regulatory factors. Signaling ... ...

    Abstract Reactive oxygen species (ROS) regulate the strength and duration of signaling through redox-dependent signal transduction pathways via the cyclic oxidation/reduction of cysteine residues in kinases, phosphatases, and other regulatory factors. Signaling circuits may be segregated in organelles or other subcellular domains with distinct redox states, permitting them to respond independently to changes in the oxidation state of two major thiol reductants, glutathione and thioredoxin. Studies in yeast, and in complex eukaryotes, show that oscillations in oxygen consumption, energy metabolism, and redox state are intimately integrated with cell cycle progression. Because signaling pathways play specific roles in different phases of the cell cycle and the hierarchy of redox-dependent regulatory checkpoints changes during cell cycle progression, the effects of ROS on cell fate vary during the cell cycle. In G1, ROS stimulate mitogenic pathways that control the activity of cyclin-dependent kinases (CDKs) and phosphorylation of the retinoblastoma protein (pRB), thereby regulating S-phase entry. In response to oxidative stress, Nrf2 and Foxo3a promote cell survival by inducing the expression of antioxidant enzymes and factors involved in cell cycle withdrawal, such as the cyclin-dependent kinase inhibitor (CKI) p27. In S phase, ROS induce S-phase arrest via PP2A-dependent dephosphorylation of pRB. In precancerous cells, unconstrained mitogenic signaling by activated oncogenes induces replication stress in S phase, which activates the DNA-damage response and induces cell senescence. A number of studies suggest that interactions of ROS with the G1 CDK/CKI network play a fundamental role in senescence, which is considered a barrier to tumorigenesis. Adaptive responses and loss of checkpoint proteins such as p53 and p16(INK4a) allow tumor cells to tolerate constitutive mitogenic signaling and enhanced production of ROS, leading to altered redox status in many fully transformed cells. Alterations in oxidant and energy metabolism of cancer cells have emerged as fertile ground for new therapeutic targets. The present challenge is to identify redox-dependent targets relevant to each cell cycle phase, to understand how these targets control fate decisions, and to describe the mechanisms that link metabolism to cell cycle progression.
    MeSH term(s) Animals ; Cell Cycle/physiology ; Cell Cycle Proteins/metabolism ; Humans ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Signal Transduction/physiology
    Chemical Substances Cell Cycle Proteins ; Reactive Oxygen Species
    Language English
    Publishing date 2009-05-29
    Publishing country United States
    Document type Journal Article ; Review
    ZDB-ID 807032-5
    ISSN 1873-4596 ; 0891-5849
    ISSN (online) 1873-4596
    ISSN 0891-5849
    DOI 10.1016/j.freeradbiomed.2009.05.026
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Acetic acid effects on aging in budding yeast: are they relevant to aging in higher eukaryotes?

    Burhans, William C / Weinberger, Martin

    Cell cycle (Georgetown, Tex.)

    2009  Volume 8, Issue 14, Page(s) 2300–2302

    MeSH term(s) Acetic Acid/metabolism ; Aging ; Animals ; G1 Phase ; Hydrogen-Ion Concentration ; Osmolar Concentration ; Protein Kinases/metabolism ; Saccharomycetales/metabolism ; Signal Transduction ; Somatomedins/metabolism ; Superoxide Dismutase/metabolism
    Chemical Substances Somatomedins ; Superoxide Dismutase (EC 1.15.1.1) ; superoxide dismutase 2 (EC 1.15.1.1) ; Protein Kinases (EC 2.7.-) ; SCH9 protein kinase (EC 2.7.1.-) ; Acetic Acid (Q40Q9N063P)
    Language English
    Publishing date 2009-07-27
    Publishing country United States
    Document type Comment ; Letter ; Research Support, N.I.H., Extramural
    ZDB-ID 2146183-1
    ISSN 1551-4005 ; 1538-4101 ; 1554-8627
    ISSN (online) 1551-4005
    ISSN 1538-4101 ; 1554-8627
    DOI 10.4161/cc.8.14.8852
    Database MEDical Literature Analysis and Retrieval System OnLINE

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