Inflammation, Aging and Cancer

Inflammation, Aging and Cancer

Author: Mahin Khatami

Publisher: Springer

Published: 2018-01-17

Total Pages: 389

ISBN-13: 3319664751

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This book was prepared as extension of author’s accidental discoveries on experimental models of acute and chronic ocular inflammatory diseases that were established at the University of Pennsylvania in 1980’s. Analyses of original data suggest a series of first evidence for direct link between inflammation and developmental phases of immune dysfunction in multistep tumorigenesis and angiogenesis. The only evidence presented on initial events for interactions and synergies between activated host and recruiting cells toward tumorigenesis. Effective immunity was defined as balance between two highly regulated and biologically opposing arms, Yin and Yang of acute inflammation, an amazingly precise signal communications between immune and non-immune systems requiring differential bioenergetics. Unresolved inflammation is a common denominator mapping aging process and induction of ‘mild’, ‘moderate’ or ‘severe’ immune disorders including cancers. Our knowledge of the fascinating biology of immunity in health or chronic diseases is fragmentary, chaotic and confusing, particularly for cancer science. Lack of progress in curing majority of chronic diseases or cancer is primarily due to the fact that scientists work on isolated molecules/cells or topics that are funded and promoted by decision makers in medical/cancer establishment. Despite existence of over 25 million articles on cancer-related topics, cancer biology and cure remain mysteries to be solved. After a century of cancer research, the failure rates of therapies for solid tumors are 90% (+/-5). Current reductionist views on cancer science are irresponsible, shut-gun approaches and create chaos. Outcomes are loss of millions of precious lives and economic drain to society. Very little is known about initial events that disturb effective immunity whose function is to monitor and arrest growth of cancerous cells or defend against other external or internal hazardous agents that threaten body’s survival. The author demonstrates the serious need for systematic understanding of how immune disruptors and aging process would alter effective immunity. Outcomes of proposed orderly studies are expected to provide logical foundations for cost-effective strategies to promote immunity toward a healthier society. The policy makers and medical/cancer establishment are urged to return to the common sense that our Forefathers used to serve the public.


Book Synopsis Inflammation, Aging and Cancer by : Mahin Khatami

Download or read book Inflammation, Aging and Cancer written by Mahin Khatami and published by Springer. This book was released on 2018-01-17 with total page 389 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book was prepared as extension of author’s accidental discoveries on experimental models of acute and chronic ocular inflammatory diseases that were established at the University of Pennsylvania in 1980’s. Analyses of original data suggest a series of first evidence for direct link between inflammation and developmental phases of immune dysfunction in multistep tumorigenesis and angiogenesis. The only evidence presented on initial events for interactions and synergies between activated host and recruiting cells toward tumorigenesis. Effective immunity was defined as balance between two highly regulated and biologically opposing arms, Yin and Yang of acute inflammation, an amazingly precise signal communications between immune and non-immune systems requiring differential bioenergetics. Unresolved inflammation is a common denominator mapping aging process and induction of ‘mild’, ‘moderate’ or ‘severe’ immune disorders including cancers. Our knowledge of the fascinating biology of immunity in health or chronic diseases is fragmentary, chaotic and confusing, particularly for cancer science. Lack of progress in curing majority of chronic diseases or cancer is primarily due to the fact that scientists work on isolated molecules/cells or topics that are funded and promoted by decision makers in medical/cancer establishment. Despite existence of over 25 million articles on cancer-related topics, cancer biology and cure remain mysteries to be solved. After a century of cancer research, the failure rates of therapies for solid tumors are 90% (+/-5). Current reductionist views on cancer science are irresponsible, shut-gun approaches and create chaos. Outcomes are loss of millions of precious lives and economic drain to society. Very little is known about initial events that disturb effective immunity whose function is to monitor and arrest growth of cancerous cells or defend against other external or internal hazardous agents that threaten body’s survival. The author demonstrates the serious need for systematic understanding of how immune disruptors and aging process would alter effective immunity. Outcomes of proposed orderly studies are expected to provide logical foundations for cost-effective strategies to promote immunity toward a healthier society. The policy makers and medical/cancer establishment are urged to return to the common sense that our Forefathers used to serve the public.


Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Author: M. A. Hayat

Publisher: Academic Press

Published: 2016-12-28

Total Pages: 430

ISBN-13: 0128094273

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Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. Presents the most advanced information regarding the role of the autophagic system in life and death Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available


Book Synopsis Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging by : M. A. Hayat

Download or read book Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging written by M. A. Hayat and published by Academic Press. This book was released on 2016-12-28 with total page 430 pages. Available in PDF, EPUB and Kindle. Book excerpt: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging is an eleven volume series that discusses in detail all aspects of autophagy machinery in the context of health, cancer, and other pathologies. Autophagy maintains homeostasis during starvation or stress conditions by balancing the synthesis of cellular components and their deregulation by autophagy. This series discusses the characterization of autophagosome-enriched vaccines and its efficacy in cancer immunotherapy. Autophagy serves to maintain healthy cells, tissues, and organs, but also promotes cancer survival and growth of established tumors. Impaired or deregulated autophagy can also contribute to disease pathogenesis. Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and forward-thinking, these books offer a valuable guide to cellular processes while also inciting researchers to explore their potentially important connections. Presents the most advanced information regarding the role of the autophagic system in life and death Examines whether autophagy acts fundamentally as a cell survivor or cell death pathway or both Introduces new, more effective therapeutic strategies in the development of targeted drugs and programmed cell death, providing information that will aid in preventing detrimental inflammation Features recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities, including atherosclerosis and CNS tumors, and their development and treatment Includes chapters authored by leaders in the field around the globe—the broadest, most expert coverage available


Inflammation, Chronic Diseases and Cancer

Inflammation, Chronic Diseases and Cancer

Author: Mahin Khatami

Publisher: IntechOpen

Published: 2012-03-09

Total Pages: 444

ISBN-13: 9789535101024

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This book is a collection of excellent reviews and perspectives contributed by experts in the multidisciplinary field of basic science, clinical studies and treatment options for a wide range of acute and chronic inflammatory diseases or cancer. The goal has been to demonstrate that persistent or chronic (unresolved or subclinical) inflammation is a common denominator in the genesis, progression and manifestation of many illnesses and/or cancers, particularly during the aging process. Understanding the fundamental basis of shared and interrelated immunological features of unresolved inflammation in initiation and progression of chronic diseases or cancer are expected to hold real promises when the designs of cost-effective strategies are considered for diagnosis, prevention or treatment of a number of age-associated illnesses such as autoimmune and neurodegenerative diseases as well as many cancers.


Book Synopsis Inflammation, Chronic Diseases and Cancer by : Mahin Khatami

Download or read book Inflammation, Chronic Diseases and Cancer written by Mahin Khatami and published by IntechOpen. This book was released on 2012-03-09 with total page 444 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a collection of excellent reviews and perspectives contributed by experts in the multidisciplinary field of basic science, clinical studies and treatment options for a wide range of acute and chronic inflammatory diseases or cancer. The goal has been to demonstrate that persistent or chronic (unresolved or subclinical) inflammation is a common denominator in the genesis, progression and manifestation of many illnesses and/or cancers, particularly during the aging process. Understanding the fundamental basis of shared and interrelated immunological features of unresolved inflammation in initiation and progression of chronic diseases or cancer are expected to hold real promises when the designs of cost-effective strategies are considered for diagnosis, prevention or treatment of a number of age-associated illnesses such as autoimmune and neurodegenerative diseases as well as many cancers.


Understanding Microinflammation

Understanding Microinflammation

Author: Kenneth B. Johnson

Publisher: CreateSpace

Published: 2014-06-23

Total Pages: 296

ISBN-13: 9781482735383

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Compelling new information reveals that the root of the diseases we fear most—premature aging, cancer, and coronary disease—are intimately linked to one another by a damaging and lethal process known as microinflammation. As the name implies, microinflammation is an invisible and insidious insult to our bodies whereby inflammation occurs at the microscopic level and produces chronic damage to our cells that impairs their ability to function normally. As a result, this leads to premature aging, cholesterol plaque build-up in our arteries that produces heart disease, and cell mutation that produces cancer. Understanding Microinflammation not only provides a detailed, eye-opening examination of these devastating consequences of cellular inflammation, but also highlights the science behind the lifestyle modifications, nutritional supplements, and medicines that can be used to combat the deadly microinflammatory process.


Book Synopsis Understanding Microinflammation by : Kenneth B. Johnson

Download or read book Understanding Microinflammation written by Kenneth B. Johnson and published by CreateSpace. This book was released on 2014-06-23 with total page 296 pages. Available in PDF, EPUB and Kindle. Book excerpt: Compelling new information reveals that the root of the diseases we fear most—premature aging, cancer, and coronary disease—are intimately linked to one another by a damaging and lethal process known as microinflammation. As the name implies, microinflammation is an invisible and insidious insult to our bodies whereby inflammation occurs at the microscopic level and produces chronic damage to our cells that impairs their ability to function normally. As a result, this leads to premature aging, cholesterol plaque build-up in our arteries that produces heart disease, and cell mutation that produces cancer. Understanding Microinflammation not only provides a detailed, eye-opening examination of these devastating consequences of cellular inflammation, but also highlights the science behind the lifestyle modifications, nutritional supplements, and medicines that can be used to combat the deadly microinflammatory process.


Inflammation and Cancer

Inflammation and Cancer

Author: Bharat B. Aggarwal

Publisher: Springer

Published: 2014-05-12

Total Pages: 489

ISBN-13: 3034808372

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This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.


Book Synopsis Inflammation and Cancer by : Bharat B. Aggarwal

Download or read book Inflammation and Cancer written by Bharat B. Aggarwal and published by Springer. This book was released on 2014-05-12 with total page 489 pages. Available in PDF, EPUB and Kindle. Book excerpt: This volume examines in detail the role of chronic inflammatory processes in the development of several types of cancer. Leading experts describe the latest results of molecular and cellular research on infection, cancer-related inflammation and tumorigenesis. Further, the clinical significance of these findings in preventing cancer progression and approaches to treating the diseases are discussed. Individual chapters cover cancer of the lung, colon, breast, brain, head and neck, pancreas, prostate, bladder, kidney, liver, cervix and skin as well as gastric cancer, sarcoma, lymphoma, leukemia and multiple myeloma.


Inflammation, Advancing Age and Nutrition

Inflammation, Advancing Age and Nutrition

Author: Irfan Rahman

Publisher: Academic Press

Published: 2013-09-03

Total Pages: 383

ISBN-13: 0123978076

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The book provides a comprehensive overview to understanding the integrated impact of the concepts of cellular and molecular aspects, models, environmental factors, and lifestyle involved in premature aging. Additionally, it examines how functional food, dietary nutraceuticals or pharmacological compounds can reverse inflammation and premature aging based on personalized medicine. This book is a valuable resource for health professionals, scientists and researchers, nutritionists, health practitioners, students and for all those who wish to broaden their knowledge in the allied field. Includes models of aging, including worm, mouse and human Explores the relationship of inflammation with diseases, including ocular health, Alzheimer's and Parkinson's disease, and muscle health Encompasses a variety of lifestyle impacts, including diet, exercise and nutrition Includes suggested nutritional interventions


Book Synopsis Inflammation, Advancing Age and Nutrition by : Irfan Rahman

Download or read book Inflammation, Advancing Age and Nutrition written by Irfan Rahman and published by Academic Press. This book was released on 2013-09-03 with total page 383 pages. Available in PDF, EPUB and Kindle. Book excerpt: The book provides a comprehensive overview to understanding the integrated impact of the concepts of cellular and molecular aspects, models, environmental factors, and lifestyle involved in premature aging. Additionally, it examines how functional food, dietary nutraceuticals or pharmacological compounds can reverse inflammation and premature aging based on personalized medicine. This book is a valuable resource for health professionals, scientists and researchers, nutritionists, health practitioners, students and for all those who wish to broaden their knowledge in the allied field. Includes models of aging, including worm, mouse and human Explores the relationship of inflammation with diseases, including ocular health, Alzheimer's and Parkinson's disease, and muscle health Encompasses a variety of lifestyle impacts, including diet, exercise and nutrition Includes suggested nutritional interventions


Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Author: M. A. Hayat

Publisher: Academic Press

Published: 2013-12-26

Total Pages: 432

ISBN-13: 0124055346

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Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and up-to-date, this book offers a valuable guide to these cellular processes whilst encouraging researchers to explore their potentially important connections. Volume 3 explores the role of autophagy in specific diseases and developments, including: Crohn’s Disease, Gaucher Disease, Huntington’s Disease, HCV infection, osteoarthritis, and liver injury. A full section is devoted to in-depth exploration of autophagy in tumor development and cancer. Finally, the work explores the relationship between autophagy and apoptosis, with attention to the ways in which autophagy regulates apoptosis, and the ways in which autophagy has been explored in Lepidoptera, elucidating the use of larval midgut as a model for such exploration. From these well-developed foundations, researchers, translational scientists, and practitioners may work to better implement more effective therapies against some of the most devastating human diseases. Volumes in the Series


Book Synopsis Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging by : M. A. Hayat

Download or read book Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging written by M. A. Hayat and published by Academic Press. This book was released on 2013-12-26 with total page 432 pages. Available in PDF, EPUB and Kindle. Book excerpt: Understanding the importance and necessity of the role of autophagy in health and disease is vital for the studies of cancer, aging, neurodegeneration, immunology, and infectious diseases. Comprehensive and up-to-date, this book offers a valuable guide to these cellular processes whilst encouraging researchers to explore their potentially important connections. Volume 3 explores the role of autophagy in specific diseases and developments, including: Crohn’s Disease, Gaucher Disease, Huntington’s Disease, HCV infection, osteoarthritis, and liver injury. A full section is devoted to in-depth exploration of autophagy in tumor development and cancer. Finally, the work explores the relationship between autophagy and apoptosis, with attention to the ways in which autophagy regulates apoptosis, and the ways in which autophagy has been explored in Lepidoptera, elucidating the use of larval midgut as a model for such exploration. From these well-developed foundations, researchers, translational scientists, and practitioners may work to better implement more effective therapies against some of the most devastating human diseases. Volumes in the Series


Inflammation, Chronic Diseases and Cancer

Inflammation, Chronic Diseases and Cancer

Author: Mahin Khatami

Publisher: BoD – Books on Demand

Published: 2012-03-09

Total Pages: 446

ISBN-13: 9535101021

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This book is a collection of excellent reviews and perspectives contributed by experts in the multidisciplinary field of basic science, clinical studies and treatment options for a wide range of acute and chronic inflammatory diseases or cancer. The goal has been to demonstrate that persistent or chronic (unresolved or subclinical) inflammation is a common denominator in the genesis, progression and manifestation of many illnesses and/or cancers, particularly during the aging process. Understanding the fundamental basis of shared and interrelated immunological features of unresolved inflammation in initiation and progression of chronic diseases or cancer are expected to hold real promises when the designs of cost-effective strategies are considered for diagnosis, prevention or treatment of a number of age-associated illnesses such as autoimmune and neurodegenerative diseases as well as many cancers.


Book Synopsis Inflammation, Chronic Diseases and Cancer by : Mahin Khatami

Download or read book Inflammation, Chronic Diseases and Cancer written by Mahin Khatami and published by BoD – Books on Demand. This book was released on 2012-03-09 with total page 446 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book is a collection of excellent reviews and perspectives contributed by experts in the multidisciplinary field of basic science, clinical studies and treatment options for a wide range of acute and chronic inflammatory diseases or cancer. The goal has been to demonstrate that persistent or chronic (unresolved or subclinical) inflammation is a common denominator in the genesis, progression and manifestation of many illnesses and/or cancers, particularly during the aging process. Understanding the fundamental basis of shared and interrelated immunological features of unresolved inflammation in initiation and progression of chronic diseases or cancer are expected to hold real promises when the designs of cost-effective strategies are considered for diagnosis, prevention or treatment of a number of age-associated illnesses such as autoimmune and neurodegenerative diseases as well as many cancers.


Aging and Health

Aging and Health

Author: Anatoli I. Yashin

Publisher:

Published: 2015

Total Pages: 0

ISBN-13: 9783318027297

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Aging is a major risk factor for chronic diseases, which in turn can provide information about the aging of a biological system. This publication serves as an introduction to systems biology and its application to biological aging. Key pathways and processes that impinge on aging are reviewed, and how they contribute to health and disease during aging is discussed. The evolution of this situation is analyzed, and the consequences for the study of genetic effects on aging are presented. Epigenetic programming of aging, as a continuation of development, creates an interface between the genome and the environment. New research into the gut microbiome describes how this interface may operate in practice with marked consequences for a variety of disorders. This analysis is bolstered by a view of the aging organism as a whole, with conclusions about the mechanisms underlying resilience of the organism to change, and is expanded with a discussion of circadian rhythms in aging. Finally, the book presents an outlook for the development of interventions to delay or to reverse the features of aging. The publication is recommended to students, researchers as well as professionals dealing with public health and public policy related to an aging society.


Book Synopsis Aging and Health by : Anatoli I. Yashin

Download or read book Aging and Health written by Anatoli I. Yashin and published by . This book was released on 2015 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Aging is a major risk factor for chronic diseases, which in turn can provide information about the aging of a biological system. This publication serves as an introduction to systems biology and its application to biological aging. Key pathways and processes that impinge on aging are reviewed, and how they contribute to health and disease during aging is discussed. The evolution of this situation is analyzed, and the consequences for the study of genetic effects on aging are presented. Epigenetic programming of aging, as a continuation of development, creates an interface between the genome and the environment. New research into the gut microbiome describes how this interface may operate in practice with marked consequences for a variety of disorders. This analysis is bolstered by a view of the aging organism as a whole, with conclusions about the mechanisms underlying resilience of the organism to change, and is expanded with a discussion of circadian rhythms in aging. Finally, the book presents an outlook for the development of interventions to delay or to reverse the features of aging. The publication is recommended to students, researchers as well as professionals dealing with public health and public policy related to an aging society.


Aging, Obesity, and Inflammation

Aging, Obesity, and Inflammation

Author: Annie Mirsoian

Publisher:

Published: 2016

Total Pages:

ISBN-13: 9781339824147

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The use of immunotherapy (IT) in cancer has recently resulted in impressive responses. Yet, their usages, especially those involving cytokine therapies, have also resulted in the induction of severe systemic toxicities often not previously characterized in their preclinical animal studies. The vast majority of murine cancer studies are performed using young, lean, SPF inbred mice yet human cancer is a disease of the aged with majority of patients being over the age of 55 with varying levels of body mass indexes and pre-existing inflammatory profiles from lifelong antigen exposure. Here, we determine the effects of adiposity on systemic immunotherapy tolerance in aged compared to young obese mice. Both young ob/ob and DIO generated pro-inflammatory cytokine levels and organ pathologies comparable to aged ad-libitum mice following immunotherapy, culminating in lethality. Caloric-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality. Our data demonstrates that accounting for the chronic, low-grade, persistent inflammatory profile that is present within aging and obesity renders effects that have similarly been observed in clinical trials with systemic cytokine therapies. Additionally, our studies sought to determine the consequences of pre-existing inflammatory profiles present within obesity and aging on T cell activation and exhaustion to determine if similar effects would be induced by other immunotherapy regimens, namely checkpoint blockade. We show through protein and gene microarray analyses that both obesity and aging result in an exhaustive phenotype within CD4 T cells. However, aged mice displayed characteristics that correlated with a terminal exhaustion phenotype where as CD4 T cells from obese were only partially exhausted. These important molecular insights provide the potential for increased targeting with checkpoint blockade therapy that could be harnessed to reinvigorate anti-tumor responses. Together, our data demonstrates that it is increasingly imperative for measurement of both efficacy as well as toxicity to be conducted in models of appropriate demographics.


Book Synopsis Aging, Obesity, and Inflammation by : Annie Mirsoian

Download or read book Aging, Obesity, and Inflammation written by Annie Mirsoian and published by . This book was released on 2016 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: The use of immunotherapy (IT) in cancer has recently resulted in impressive responses. Yet, their usages, especially those involving cytokine therapies, have also resulted in the induction of severe systemic toxicities often not previously characterized in their preclinical animal studies. The vast majority of murine cancer studies are performed using young, lean, SPF inbred mice yet human cancer is a disease of the aged with majority of patients being over the age of 55 with varying levels of body mass indexes and pre-existing inflammatory profiles from lifelong antigen exposure. Here, we determine the effects of adiposity on systemic immunotherapy tolerance in aged compared to young obese mice. Both young ob/ob and DIO generated pro-inflammatory cytokine levels and organ pathologies comparable to aged ad-libitum mice following immunotherapy, culminating in lethality. Caloric-restricted aged mice contain less visceral fat and displayed reduced cytokine levels, protection from organ pathology, and protection from lethality. Our data demonstrates that accounting for the chronic, low-grade, persistent inflammatory profile that is present within aging and obesity renders effects that have similarly been observed in clinical trials with systemic cytokine therapies. Additionally, our studies sought to determine the consequences of pre-existing inflammatory profiles present within obesity and aging on T cell activation and exhaustion to determine if similar effects would be induced by other immunotherapy regimens, namely checkpoint blockade. We show through protein and gene microarray analyses that both obesity and aging result in an exhaustive phenotype within CD4 T cells. However, aged mice displayed characteristics that correlated with a terminal exhaustion phenotype where as CD4 T cells from obese were only partially exhausted. These important molecular insights provide the potential for increased targeting with checkpoint blockade therapy that could be harnessed to reinvigorate anti-tumor responses. Together, our data demonstrates that it is increasingly imperative for measurement of both efficacy as well as toxicity to be conducted in models of appropriate demographics.