Author:
Publisher: BoD – Books on Demand
ISBN: 183969050X
Category : Psychology
Languages : en
Pages : 132
Book Description
Senescence represents a complex universal phenomenon that can be impacted by several factors. It is emerging as a therapeutic target for several diseases. This book presents an overview of the current mechanisms and management of senescence in humans. It also provides comparative data on senescence in animals and plants.
Mechanisms and Management of Senescence
Author:
Publisher: BoD – Books on Demand
ISBN: 183969050X
Category : Psychology
Languages : en
Pages : 132
Book Description
Senescence represents a complex universal phenomenon that can be impacted by several factors. It is emerging as a therapeutic target for several diseases. This book presents an overview of the current mechanisms and management of senescence in humans. It also provides comparative data on senescence in animals and plants.
Publisher: BoD – Books on Demand
ISBN: 183969050X
Category : Psychology
Languages : en
Pages : 132
Book Description
Senescence represents a complex universal phenomenon that can be impacted by several factors. It is emerging as a therapeutic target for several diseases. This book presents an overview of the current mechanisms and management of senescence in humans. It also provides comparative data on senescence in animals and plants.
Molecular Mechanisms of Cellular Senescence
Author: Therese Becker
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages :
Book Description
Molecular Mechanisms of Cellular Senescence.
Publisher:
ISBN:
Category : Medicine
Languages : en
Pages :
Book Description
Molecular Mechanisms of Cellular Senescence.
Molecular Mechanisms Involved in the Induction and Maintenance of Cellular Senescence
Author: Sebastian Igelmann
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
Cellular senescence is a barrier to tumor progression that is circumvented in cancer cells. Senescence is a stable cell cycle arrest and can be triggered by various oncogenic events, such as constant activation of the oncogene H-RAS. Other critical aspects of senescent cells include a specific degradation of proteins implicated in cell cycle regulation, ribosome biogenesis, mitochondrial homeostasis, and cellular metabolism. In this study, we wanted to identify the contributions of the specific protein degradation to mitochondrial homeostasis, cellular metabolism, and ribosome biogenesis and how the degradation of proteins implicated in those pathways affects the senescence response. In order to answer our question, we divided our research into two aspects. The first aspect was focused on ribosomes and the alterations in ribosome biogenesis in senescence. The second aspect was the contribution of degradation of proteins implicated in cellular metabolism and mitochondrial homeostasis. First, we identified that a desynchronization of ribosome biogenesis accompanies senescence, meaning that certain rRNA are less transcribed, whereas specific ribosomal proteins do not decrease their transcription leading to an imbalance in ribosomal protein and ribosomal RNA. This imbalance causes an accumulation of ribosomal free riboproteins. Those accumulated riboproteins acquire novel functions. We identified RPL29 as a ribosomal free riboprotein that accumulated in senescent cells and can be used as a novel biomarker to identify senescent cells in vitro and in vivo. Identification of novel senescent cell biomarkers is crucial as no specific marker of senescence is available. Furthermore, we identified RPS14 as a protein that can interact with the CDK4-cyclinD1 complex and decrease cell cycle progression. Of utmost importance is that cell cycle repression was even possible in cancer cells devoided of p53 highlighting novel strategies for p53 null cancer treatments. In the second part, we focused on alterations in cellular metabolism, particularly in light of NAD metabolism and mitochondria homeostasis. We could confirm that the degradation of proteins implicated in mitochondrial homeostasis can induce senescence via the accumulation of NADH and p53 stabilization. Furthermore, we confirmed that the decrease in redox homeostasis regulators, namely NAD+ and NADPH, can trigger senescence. In the same idea, we showed that the normalization of those redox potentials could bypass the senescence response. Most importantly, we identified a novel protein complex formed by malic enzyme, malate dehydrogenase,and pyruvate carboxylase. The concerted actions of those three metabolic enzymes can transfer the hydride ion from NADH towards NADPH. Thus, we coined this complex HTC for hydride transfer complex. These metabolic reactions in HTC allow for two things, the normalization of NAD+ levels and the normalization of NADPH levels. Intruguenlty, both NAD+ and NADPH level increase were previously linked to transformation, and indeed, we were able to show that expression of HTC in combination with oncogenic Ras is sufficient to transform primary cells. Moreover, HTC enzymes are highly expressed in vivo in mouse and human prostate cancer models, and their inactivation triggers senescence even in the absence of p53. We provide evidence for a new multi-enzymatic complex, with de novo functions that reprogram metabolism and prevent cellular senescence. Inhibition of formation of the HTC complex might allow targeting specifically the de novo function of this complex with fewer effects on normal enzyme function. All in all, we highlighted the contributions of ribosome biogenesis and metabolic alterations in inducing and maintaining the senescence response. Furthermore, RPS14 accumulation allows for a novel cell cycle regulation mechanism, and the accumulation of RPL29 in the nucleolus can be used as a novel biomarker for cellular senescence. Moreover, the expression of HTC demonstrated a novel way of avoiding senescence, thus promoting cellular transformation. Both pathways highlight the importance of cellular senescence as a tumor suppressors mechanism, and these discoveries allow for novel strategies for cancer drug development.
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
Cellular senescence is a barrier to tumor progression that is circumvented in cancer cells. Senescence is a stable cell cycle arrest and can be triggered by various oncogenic events, such as constant activation of the oncogene H-RAS. Other critical aspects of senescent cells include a specific degradation of proteins implicated in cell cycle regulation, ribosome biogenesis, mitochondrial homeostasis, and cellular metabolism. In this study, we wanted to identify the contributions of the specific protein degradation to mitochondrial homeostasis, cellular metabolism, and ribosome biogenesis and how the degradation of proteins implicated in those pathways affects the senescence response. In order to answer our question, we divided our research into two aspects. The first aspect was focused on ribosomes and the alterations in ribosome biogenesis in senescence. The second aspect was the contribution of degradation of proteins implicated in cellular metabolism and mitochondrial homeostasis. First, we identified that a desynchronization of ribosome biogenesis accompanies senescence, meaning that certain rRNA are less transcribed, whereas specific ribosomal proteins do not decrease their transcription leading to an imbalance in ribosomal protein and ribosomal RNA. This imbalance causes an accumulation of ribosomal free riboproteins. Those accumulated riboproteins acquire novel functions. We identified RPL29 as a ribosomal free riboprotein that accumulated in senescent cells and can be used as a novel biomarker to identify senescent cells in vitro and in vivo. Identification of novel senescent cell biomarkers is crucial as no specific marker of senescence is available. Furthermore, we identified RPS14 as a protein that can interact with the CDK4-cyclinD1 complex and decrease cell cycle progression. Of utmost importance is that cell cycle repression was even possible in cancer cells devoided of p53 highlighting novel strategies for p53 null cancer treatments. In the second part, we focused on alterations in cellular metabolism, particularly in light of NAD metabolism and mitochondria homeostasis. We could confirm that the degradation of proteins implicated in mitochondrial homeostasis can induce senescence via the accumulation of NADH and p53 stabilization. Furthermore, we confirmed that the decrease in redox homeostasis regulators, namely NAD+ and NADPH, can trigger senescence. In the same idea, we showed that the normalization of those redox potentials could bypass the senescence response. Most importantly, we identified a novel protein complex formed by malic enzyme, malate dehydrogenase,and pyruvate carboxylase. The concerted actions of those three metabolic enzymes can transfer the hydride ion from NADH towards NADPH. Thus, we coined this complex HTC for hydride transfer complex. These metabolic reactions in HTC allow for two things, the normalization of NAD+ levels and the normalization of NADPH levels. Intruguenlty, both NAD+ and NADPH level increase were previously linked to transformation, and indeed, we were able to show that expression of HTC in combination with oncogenic Ras is sufficient to transform primary cells. Moreover, HTC enzymes are highly expressed in vivo in mouse and human prostate cancer models, and their inactivation triggers senescence even in the absence of p53. We provide evidence for a new multi-enzymatic complex, with de novo functions that reprogram metabolism and prevent cellular senescence. Inhibition of formation of the HTC complex might allow targeting specifically the de novo function of this complex with fewer effects on normal enzyme function. All in all, we highlighted the contributions of ribosome biogenesis and metabolic alterations in inducing and maintaining the senescence response. Furthermore, RPS14 accumulation allows for a novel cell cycle regulation mechanism, and the accumulation of RPL29 in the nucleolus can be used as a novel biomarker for cellular senescence. Moreover, the expression of HTC demonstrated a novel way of avoiding senescence, thus promoting cellular transformation. Both pathways highlight the importance of cellular senescence as a tumor suppressors mechanism, and these discoveries allow for novel strategies for cancer drug development.
Myeloid Malignancies
Author: Barbara J. Bain
Publisher: Clinical Pub
ISBN: 9781846920554
Category : Blood
Languages : en
Pages : 0
Book Description
Aimed at meeting the needs for haematologists and clinical chemists for a reference, this atlas offers a visual presentation of myeloproliferative neoplasms and myeloid leukaemia. It surveys individual disease, covering the clinical presentation, haematological and pathological features, immunophenotyping and cytogenetic and genetic abnormalities.
Publisher: Clinical Pub
ISBN: 9781846920554
Category : Blood
Languages : en
Pages : 0
Book Description
Aimed at meeting the needs for haematologists and clinical chemists for a reference, this atlas offers a visual presentation of myeloproliferative neoplasms and myeloid leukaemia. It surveys individual disease, covering the clinical presentation, haematological and pathological features, immunophenotyping and cytogenetic and genetic abnormalities.
Frailty and Cardiovascular Diseases
Author: Nicola Veronese
Publisher: Springer Nature
ISBN: 3030333302
Category : Medical
Languages : en
Pages : 154
Book Description
This book aims to clarify the potential association between frailty and cardiovascular disease in older people. Covering the biological as well as the clinical point of view, it allows researchers and clinicians to discover the significance of this topic. The contributions cover the most important aspects in the potential relationship between frailty and cardiovascular disease. In particular, authoritative authors in this field have clarified the definition and the epidemiology of frailty and cardiovascular disease in older people. A large part of the volume is dedicated to the biological mechanisms of frailty and cardiovascular disease, trying to find those in common between these two conditions. Since this book is dedicated to both researchers and clinicians, we have proposed some chapters to the importance of comprehensive geriatric assessment in the evaluation and treatment of cardiovascular diseases and frailty. In this regard, the importance of geriatric evaluation in cardiac surgery for older people is well covered. Finally, the importance of cardiac rehabilitation and physical exercise is summarized, being, actually, the most important treatments for both frailty and cardiovascular disease. Written by many well-known and widely published experts in their respective fields, this book will appeal to a wide readership such as researchers in the field and clinicians, especially suited in geriatric medicine and cardiology who, every day, face frail older patients.
Publisher: Springer Nature
ISBN: 3030333302
Category : Medical
Languages : en
Pages : 154
Book Description
This book aims to clarify the potential association between frailty and cardiovascular disease in older people. Covering the biological as well as the clinical point of view, it allows researchers and clinicians to discover the significance of this topic. The contributions cover the most important aspects in the potential relationship between frailty and cardiovascular disease. In particular, authoritative authors in this field have clarified the definition and the epidemiology of frailty and cardiovascular disease in older people. A large part of the volume is dedicated to the biological mechanisms of frailty and cardiovascular disease, trying to find those in common between these two conditions. Since this book is dedicated to both researchers and clinicians, we have proposed some chapters to the importance of comprehensive geriatric assessment in the evaluation and treatment of cardiovascular diseases and frailty. In this regard, the importance of geriatric evaluation in cardiac surgery for older people is well covered. Finally, the importance of cardiac rehabilitation and physical exercise is summarized, being, actually, the most important treatments for both frailty and cardiovascular disease. Written by many well-known and widely published experts in their respective fields, this book will appeal to a wide readership such as researchers in the field and clinicians, especially suited in geriatric medicine and cardiology who, every day, face frail older patients.
Cellular Senescence
Author:
Publisher:
ISBN:
Category : Cell physiology
Languages : en
Pages : 0
Book Description
Cellular senescence is a unique molecular mechanism with characteristics and consequences that vary greatly across distinct physiological contexts. Definitionally, senescence represents a retreat from cellular division to a viable limbo state with altered cellular metabolism and secretory patterns. Immune clearance of the senescent unit typically follows suit. This pattern would seem to contribute to appropriate tissue turnover, a phenomenon favorable with regard to wound healing, tissue regeneration, and tumor suppression. It is therefore intriguing to consider the contributions of senescence to various disease states including age-related degenerations and even cancer itself, the very condition against which senescence is thought to be protective. To better elucidate the apparent contradictions within the conversation of senescence, this paper highlights key features of senescence as it relates to healthy embryonic development, cancer, and age-related physiological deteriorations.
Publisher:
ISBN:
Category : Cell physiology
Languages : en
Pages : 0
Book Description
Cellular senescence is a unique molecular mechanism with characteristics and consequences that vary greatly across distinct physiological contexts. Definitionally, senescence represents a retreat from cellular division to a viable limbo state with altered cellular metabolism and secretory patterns. Immune clearance of the senescent unit typically follows suit. This pattern would seem to contribute to appropriate tissue turnover, a phenomenon favorable with regard to wound healing, tissue regeneration, and tumor suppression. It is therefore intriguing to consider the contributions of senescence to various disease states including age-related degenerations and even cancer itself, the very condition against which senescence is thought to be protective. To better elucidate the apparent contradictions within the conversation of senescence, this paper highlights key features of senescence as it relates to healthy embryonic development, cancer, and age-related physiological deteriorations.
Mechanisms of Cellular Senescence and the Use of Repurposed Drugs as Senotherapeutic Compounds
Author: L. Bramwell
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
Publisher:
ISBN:
Category :
Languages : en
Pages : 0
Book Description
Mechanisms Leading to Escape from Oncogene-induced Senescence
Author: Priyanka L. Patel
Publisher:
ISBN:
Category :
Languages : en
Pages : 284
Book Description
Publisher:
ISBN:
Category :
Languages : en
Pages : 284
Book Description
Molecular Mechanisms of Aging
Author: Konrad Beyreuther
Publisher: Springer Science & Business Media
ISBN: 3642842240
Category : Medical
Languages : en
Pages : 327
Book Description
Publisher: Springer Science & Business Media
ISBN: 3642842240
Category : Medical
Languages : en
Pages : 327
Book Description
The Functional Nucleus
Author: David P. Bazett-Jones
Publisher: Springer
ISBN: 3319388827
Category : Science
Languages : en
Pages : 501
Book Description
This book gives an in-depth overview on nuclear structure and function. It clearly shows that the epigenome and the three-dimensional organization of the nucleus are not independent properties. The intimate relationship between the location and the epigenetic modifications of gene loci is highlighted. Finally, it shows that the complex three-dimensional organization of the nucleus is not just of academic interest: The structure, composition and function of virtually all of the sub-nuclear compartments identified so far can be implicated to a list of human genetic diseases. Hence, a detailed elucidation of how these domains are assembled and function will provide new opportunities for therapeutic intervention in clinical practice.
Publisher: Springer
ISBN: 3319388827
Category : Science
Languages : en
Pages : 501
Book Description
This book gives an in-depth overview on nuclear structure and function. It clearly shows that the epigenome and the three-dimensional organization of the nucleus are not independent properties. The intimate relationship between the location and the epigenetic modifications of gene loci is highlighted. Finally, it shows that the complex three-dimensional organization of the nucleus is not just of academic interest: The structure, composition and function of virtually all of the sub-nuclear compartments identified so far can be implicated to a list of human genetic diseases. Hence, a detailed elucidation of how these domains are assembled and function will provide new opportunities for therapeutic intervention in clinical practice.