Mechanisms Underlying Longevity Regulation and Extension by Genetic, Dietary and Pharmacological Interventions in the Yeast Saccharomyces Cerevisiae PDF Download

Author: Pavlo Kyryakov
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Vladimir I. Titorenko
Publisher: Frontiers E-books
ISBN: 2889190900
Category :
Languages : en
Pages : 102

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Aging of multicellular and unicellular eukaryotic organisms is a highly complex biological phenomenon that affects a plethora of processes within cells. This wide array of longevity-defining cellular processes - which are governed by an evolutionarily conserved signaling network - includes oxidative metabolism and protein synthesis in mitochondria, lipid and carbohydrate metabolism, NAD+ homeostasis, amino acid biosynthesis and degradation, ammonium and amino acid uptake, ribosome biogenesis and translation, proteasomal protein degradation, nuclear DNA replication, chromatin assembly and maintenance, actin organization, apoptosis, necrosis, autophagy, protein folding, stress response, signal transduction, cell cycle, and cell growth. The focus of this Frontiers Special Topic Issue is on an important conceptual advance in our understanding of how cells integrate and control these numerous processes and how genetic, dietary and pharmacological anti-aging interventions extend longevity by altering their functional states and spatiotemporal dynamics. The Issue will highlight the various strategies used by evolutionarily diverse organisms for coordinating these longevity-defining cellular processes in space and time, critically evaluate the molecular and cellular mechanisms underlying such coordination, and outline the most important unanswered questions and directions for future research in this vibrant and rapidly evolving field.

Author: Anastasia Glebov
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Anthony Arlia Ciommo
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Author: Craig Brendon Skinner
Publisher:
ISBN: 9781124908489
Category :
Languages : en
Pages :

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The search for the fountain of youth, undertaken by Juan Ponce de Leon in the 16th century and continued by longevity researchers around the globe, has evolved from a seemingly impossible expedition into the pursuit of a very real phenomenon: the life span-extending dietary regimen of calorie restriction (CR), and knowledge of its mechanism. CR in mammals is known to promote longevity and delay the onset of age-related diseases such as cancer and diabetes, while promoting processes such as mitochondrial respiration and the oxidative stress response. CR extends the life span of a wide variety of model organisms including worms, flies, mice, and monkeys, but many of the greatest revelations came from an unlikely place, the single-celled budding yeast Saccharomyces cerevisiae. The determination and characterization of many important longevity pathway components originated from studies on this humble organism. Mitochondrial respiration and stability are critical to CR-based life span extension, and are central to longevity in budding yeast, as they are in mammals. Mitochondria promote long life through activation of sirtuins, a family of NAD+-dependent protein deacetylases, and promotion of metabolic health, but also mediate cell death through apoptosis. They are the cellular reactors, capable of immensely efficient energy harvesting, yet produce the majority of cellular free radicals which, when unchecked, can cause irreparable damage to cellular machinery. Unsurprisingly, life span extending manipulations often impact the status of this organelle, often in ways similar to those of CR. Life span prolonging manipulations in budding yeast are often resistant to reactive oxygen species (ROS), which are associated with mitochondrial decline during the aging process. Originally identified as a mediator of cell size in budding yeast, cells without WHI2 continue to grow in stationary phase, possess unstable mitochondria, and display sensitivities to a wide variety of stresses, including oxidative stress. A screen for long-lived yeast revealed WHI2 as a life span-extending gene when over-expressed, and here we determine that WHI2 is a dosage-dependent mediator of longevity. Additionally, Whi2 requires the Msn2/4 transcription factors and Psr1/2 phosphatases for full life span extension. Psr1/2 was also found to mediate stability of Whi2 protein after the diauxic shift and into stationary phase, where the Whi2 phenotype is the most evident. Whi2 also regulates activation of Hsf1 transcription factor, and between Msn2/4 and Hsf1, promotes the oxidative stress response to protect mitochondria during stationary phase. The interaction between Hsf1 and Whi2 is complicated, and Whi2 appears to suppress Hsf1 before the diauxic shift, yet activate it afterwards. Investigating the relationship between Whi2, Hsf1, and growth phase may help us better understand the function of Hsf1 in cancer cells and during CR. CR is characterized by an increase in mitochondrial respiration and oxidative stress defense, but also induces production of a specific ROS, nitric oxide (NO). Production of NO by CR is important in both mammals and, as determined in this volume, budding yeast. Using NO as a biomarker of CR, several single-gene deletions that share CR phenotypes were identified and verified to be novel life span-extending mutants. In addition, the mechanisms behind CR-mediated NO production in yeast was analyzed. CR-linked NO production in yeast requires a functional electron transport chain, suggesting that the origin of NO during CR is cytochrome c oxidase (COX), as COX was previously demonstrated to generate NO from nitrite. NO is therefore a mitochondria-derived life span mediating molecule, adding yet another facet to the relationship between CR and mitochondria. Life span studies in yeast continue to contribute to our understanding of the molecular mechanisms of CR and aging. The following studies should further illuminate the connection between CR, mitochondria, and longevity, and it is my hope that these new revelations will contribute to our knowledge of longevity in mammals as well.

Author: Michael Breitenbach
Publisher: Springer Science & Business Media
ISBN: 9400725612
Category : Science
Languages : en
Pages : 373

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This volume includes contributions by the leading experts in the field of yeast aging. Budding yeast (Saccharomyces cerevisiae) and other fungal organisms provide models for aging research that are relevant to organismic aging and to the aging processes occurring in the human body. Replicative aging, in which only the mother cell ages while the daughter cell resets the clock to zero is a model for the aging of stem cell populations in humans, while chronological aging (measured by survival in stationary phase) is a model for the aging processes in postmitotic cells (for instance, neurons of the brain). Most mechanisms of aging are studied in yeast. Among them, this book discusses: mitochondrial theories of aging, emphasizing oxidative stress and retrograde responses; the role of autophagy and mitophagy; the relationship of apoptosis to aging processes; the role of asymmetric segregation of damage in replicative aging; the role of replication stress; and the role of the cytoskeleton in aging. Modern methods of yeast genetics and genomics are described that can be used to search for aging-specific functions in a genome-wide unbiased fashion. The similarities in the pathology of senescence (studied in yeast) and of cancer cells, including genome instability, are examined.

Author: Siegfried Hekimi
Publisher: Springer Science & Business Media
ISBN: 354048003X
Category : Science
Languages : en
Pages : 254

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The molecular genetics of aging or life-span determination is an expanding field. One reason is because many people would consider it desirable if hu man life span could be extended. Indeed, it is difficult not to be fascinated by tales of the life and death of people who have succeeded in living a very long life. Because of this, we have placed at the head of this book the chapter by Perls et al. on Centenerians and the Genetics of Longevity. Perls and his coauthors convincingly argue that, while the average life expectancy might be mostly determined by environmental factors because the average person has an average genotype, extremely long life spans are genetically determined. Of course, studying humans to uncover the genetics of aging is not ideal, not so much because one cannot easily perform experiments as because they live such a long time. This is why most of this book describes the current state of research with model organisms such as yeast, worms, flies, and mice. J aswinski focuses on yeast and how metabolic activity and stress resistance affect the longevity of Saccharomyces cerevisiae. In the process, he discusses the concept of aging as applied to a unicellular organism such as yeast and the importance of metabolism and stress resistance for aging in all organisms.

Author: Marysia C. Kolipinski
Publisher:
ISBN:
Category : Longevity
Languages : en
Pages : 132

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"Dietary restriction (DR) is a robust, drug free intervention that has been shown to increase active and healthy lifespan across a wide range of species. ... However, the downstream mechanisms by which DR modulates lifespan remain poorly understood. My thesis focuses on identifying the role of candidate genes from these studies to identify novel pathways related to diet dependant lifespan extension." -- from the abstract, p.4.

Author: Dudley William Lamming
Publisher:
ISBN:
Category :
Languages : en
Pages : 348

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Calorie restriction (CR), a diet in which the total number of calories consumed is reduced while still maintaining adequate nutrition, can extend the lifespan of numerous organisms, including yeast, flies, worms, and mice. The effects of CR on yeast lifespan are believed to function at least in part by increasing the activity of the NAD + -dependent deacetylase Sir2, which stabilizes the yeast rDNA array and prevents the formation of extrachromosomal rDNA circles (ERCs), a cause of aging in yeast. This thesis focuses on understanding the molecular mechanisms by which CR functions to extend lifespan, understanding how this process can be regulated by the environment and on finding small molecules that can mimic the effects of CR. We identify resveratrol as an in vitro small molecule activator of yeast Sir2 and its human homologue, SIRT1. We show that resveratrol extends yeast lifespan and suppresses rDNA recombination in a Sir2-dependent manner. In humans cells, we show that resveratrol can stimulate SIRT1-dependent deacetylation of p53.

Author: P. Michael Conn
Publisher: Elsevier
ISBN: 0080460062
Category : Medical
Languages : en
Pages : 1103

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The Handbook of Models for Human Aging is designed as the only comprehensive work available that covers the diversity of aging models currently available. For each animal model, it presents key aspects of biology, nutrition, factors affecting life span, methods of age determination, use in research, and disadvantages/advantes of use. Chapters on comparative models take a broad sweep of age-related diseases, from Alzheimer's to joint disease, cataracts, cancer, and obesity. In addition, there is an historical overview and discussion of model availability, key methods, and ethical issues. - Utilizes a multidisciplinary approach - Shows tricks and approaches not available in primary publications - First volume of its kind to combine both methods of study for human aging and animal models - Over 200 illustrations