The Experts below are selected from a list of 5055 Experts worldwide ranked by ideXlab platform
Graham Pawelec - One of the best experts on this subject based on the ideXlab platform.
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A novel B cell population revealed by a CD38/CD24 gating strategy: CD38 − CD24 − B cells in centenarian offspring and elderly people
2020Co-Authors: Silvio Buffa, Graham Pawelec, Calogero Caruso, Matteo Bulati, Mariavaleria Pellicano, Adriana Martorana, David Goldeck, Giuseppina Colonna-romanoAbstract:Abstract The B cell arm of adaptive immunity undergoes significant modifications with age. Elderly people are characterized by impaired B cell responses reflected in a reduced ability to effectively respond against viruses and bacteria. Alterations of immunity with advancing age (Immunosenescence) have been widely studied in centenarians who are considered a good example of successful aging. In recent years, attention has shifted to centenarian offspring (CO) as a model of people genetically advantaged for healthy aging and longevity. Here, we describe the preliminary characterization of a proposed new population of memory B cells, defined as CD19 , which we find at higher frequencies in the elderly but less so in CO than healthy age-matched random controls. In addition, we found a decreased expression of RP105 (CD180), a toll-like receptor-associated molecule, on these cells. CD180 downregulation may potentially be a marker of Immunosenescence. Moreover, we show that these CD19 + CD38
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immune system changes and Immunosenescence
2017Co-Authors: Graham Pawelec, Ludmila Müller, Tamas Fulop, Deborah K DunnwaltersAbstract:The immune system defends against infection, but older people paradoxically suffer not only from failing immunity resulting in increased susceptibility to infections and decreased responsiveness to vaccination, but at the same time increased inflammation and immunopathology accompanying immune responses. Interventions to reduce such deleterious effects while enhancing protective immunity are challenging but need to be confronted if we are to deal successfully with the increasing numbers of elderly and frail people in modern societies. To do this, we need to understand the mechanisms responsible for age-associated increased susceptibility to infections and immune-influenced chronic degenerative diseases of ageing. Defining relevant age-associated alterations and identifying reliable biomarkers for monitoring clinically-relevant immune status in the elderly population is crucial to overcoming these problems. Here, we briefly outline age-associated changes to immunity collectively termed ‘Immunosenescence’
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age and immunity what is Immunosenescence
2017Co-Authors: Graham PawelecAbstract:As is apparent from the many contributions to this Special Issue of the Journal, the impact of age on immunity is nefarious, with all manner of dysregulated responses attributed to "Immunosenescence". These range from poorer responses to vaccination, lower capacity to mediate anti-cancer responses, more inflammation and tissue damage, along with autoimmunity and loss of control of persistent infections. Given the grave clinical implications of altered immune status in aged people, it is of paramount importance to understand the nature of and mechanisms responsible for "Immunosenescence". As in any rapidly developing research area, certain paradigms establish themselves early on, by necessity based on earlier and fewer data, and have a disproportionate influence on how investigators think about the subject, especially investigators from other disciplines. It may therefore be appropriate to reconsider our basic knowledge at this juncture, asking exactly what do we mean by the term "Immunosenescence"? This is attempted in this contribution to the Special Issue.
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intracellular signalling pathways targets to reverse Immunosenescence
2017Co-Authors: Tamas Fulop, Graham Pawelec, Carl Fortin, Jacek M Witkowski, Le A Page, Anis LarbiAbstract:Ageing is a very complex process, the result of the dysregulation of multiple systems interacting in many ways. A prominent change occurring with ageing is related to the architecture and functioning of the immune system, viewed commonly as detrimental and termed 'Immunosenescence'. However, age-associated changes may also lead to increased function in certain respects, which can be viewed as adaptive. None the less, on balance it is well-recognized that Immunosenescence is accompanied by the low-grade inflammation observed commonly in elderly people, which has been dubbed 'inflamm-ageing'. The exact cause and significance of all these changes is not clear, but there is a consensus that they are related to the occurrence of chronic non-infectious age-associated disease, as well as increased susceptibility to infections. Alterations to immune cell signalling may be a prominent cause of malfunctioning immunity. Emerging attempts to reverse Immunosenescence have recently targeted the signalling pathways in various different cell types of the immune system. Here, we review and discuss alterations in the signalling pathways of immune cells with ageing and consider current targets and means to modulate altered functions. We discuss the potential dangers as well as the benefits of these interventions, and consider future approaches to this problem.
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The Role of CMV in Immunosenescence
2016Co-Authors: Ludmila Müller, Klaus Hamprecht, Graham PawelecAbstract:The term “Immunosenescence” is commonly taken to mean age-associated changes in immune parameters hypothesized to contribute to increased susceptibility and severity of the older adult to infectious disease, autoimmunity and cancer. In humans, it is characterized by lower numbers and frequencies of naive T and B cells and higher numbers and frequencies of late-differentiated T cells, especially CD8+ T cells, in the peripheral blood. The latter may be very noticeable, but intriguingly, only in people infected by human herpesvirus 5 (Cytomegalovirus, CMV). Almost all human studies have been cross-sectional, thus documenting differences between old and young populations, but not necessarily changes over time. Nonetheless, limited longitudinal studies have provided data consistent with gradually decreasing naive T and B cells, and increasing late-differentiated T cells over time, and in rare instances associating these changes with increasing frailty and incipient mortality in the elderly. Low numbers of naive cells render the aged highly susceptible to pathogens to which they have not been previously exposed, but are not otherwise associated with an “immune risk profile” predicting earlier mortality. Whether the accumulations of late-differentiated T cells driven primarily by CMV contribute to frailty and mortality or are only adaptive responses to the persistent virus remains controversial. Either way, there is currently little direct evidence that “Immunosenescence” contributes to either autoimmunity or cancer in the aged. This chapter reviews some of the studies implicating CMV infection in Immunosenescence and its consequences for ageing trajectories in humans.
Tamas Fulop - One of the best experts on this subject based on the ideXlab platform.
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Immunosenescence and inflamm aging as two sides of the same coin friends or foes
2018Co-Authors: Tamas Fulop, Anis Larbi, Gilles Dupuis, Aurelie Le Page, Eric Frost, Alan A Cohen, Jacek M Witkowski, Claudio FranceschiAbstract:The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed Immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, Immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of Immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the Immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
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immune system changes and Immunosenescence
2017Co-Authors: Graham Pawelec, Ludmila Müller, Tamas Fulop, Deborah K DunnwaltersAbstract:The immune system defends against infection, but older people paradoxically suffer not only from failing immunity resulting in increased susceptibility to infections and decreased responsiveness to vaccination, but at the same time increased inflammation and immunopathology accompanying immune responses. Interventions to reduce such deleterious effects while enhancing protective immunity are challenging but need to be confronted if we are to deal successfully with the increasing numbers of elderly and frail people in modern societies. To do this, we need to understand the mechanisms responsible for age-associated increased susceptibility to infections and immune-influenced chronic degenerative diseases of ageing. Defining relevant age-associated alterations and identifying reliable biomarkers for monitoring clinically-relevant immune status in the elderly population is crucial to overcoming these problems. Here, we briefly outline age-associated changes to immunity collectively termed ‘Immunosenescence’
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intracellular signalling pathways targets to reverse Immunosenescence
2017Co-Authors: Tamas Fulop, Graham Pawelec, Carl Fortin, Jacek M Witkowski, Le A Page, Anis LarbiAbstract:Ageing is a very complex process, the result of the dysregulation of multiple systems interacting in many ways. A prominent change occurring with ageing is related to the architecture and functioning of the immune system, viewed commonly as detrimental and termed 'Immunosenescence'. However, age-associated changes may also lead to increased function in certain respects, which can be viewed as adaptive. None the less, on balance it is well-recognized that Immunosenescence is accompanied by the low-grade inflammation observed commonly in elderly people, which has been dubbed 'inflamm-ageing'. The exact cause and significance of all these changes is not clear, but there is a consensus that they are related to the occurrence of chronic non-infectious age-associated disease, as well as increased susceptibility to infections. Alterations to immune cell signalling may be a prominent cause of malfunctioning immunity. Emerging attempts to reverse Immunosenescence have recently targeted the signalling pathways in various different cell types of the immune system. Here, we review and discuss alterations in the signalling pathways of immune cells with ageing and consider current targets and means to modulate altered functions. We discuss the potential dangers as well as the benefits of these interventions, and consider future approaches to this problem.
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the role of Immunosenescence in the development of age related diseases
2016Co-Authors: Tamas Fulop, Gilles Dupuis, Jacek M Witkowski, Anis LarbiAbstract:Aging is a complex phenomenon leading to numerous changes in the physiological systems of the body. One of the most important changes, called Immunosenescence, occurs in the immune system. Immunosenescence covers changes in the innate and the adaptive immune systems and is associated with a low-grade inflammation called inflammaging. Aging, likely via inflammaging, is also associated with the emergence of chronic diseases including cardiovascular and neurodegenerative diseases, cancer, and diabetes mellitus type 2. The origin of this inflammaging is not known with certainty, but several concurrent contributing factors have been suggested, such as aging-associated changes in the innate and adaptive immune response, chronic antigenic stimulation, the appearance of endogenous macromolecular changes, and the presence of senescent cells exhibiting a senescence-associated secretory phenotype. A better understanding of the multiple biological phenomena leading to these diseases via the Immunosenescence associated with inflammaging provides a powerful target for interventions to increase the healthspan of elderly subjects.
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frailty inflammation and Immunosenescence
2015Co-Authors: Tamas Fulop, Graham Pawelec, Gilles Dupuis, Alan A Cohen, Jacek M Witkowski, Janet E Mcelhaney, Jose A Morais, Sarra Baehl, Xavier Camous, Anis LarbiAbstract:Frailty is a still-evolving concept of a complex phenomenon. There are several algorithms and strategies for assessing frailty syndrome, but currently, no universally accepted definition or measurement protocol has been determined. Consequently, the biological cause(s) of frailty are also poorly defined. Much circumstantial experimental data point to the dysregulation of several key physiological systems, including the neuroendocrine, musculoskeletal, metabolic and immune/inflammatory systems, resulting from alterations in functional reserves. Immune dysregulation and inflammation as causes of frailty have gained some support from the results of longitudinal studies, but a true causal relationship has not been established. This chapter will describe the immune/inflammatory alterations found in frailty and their putative causal relationships with this state.
Anis Larbi - One of the best experts on this subject based on the ideXlab platform.
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Immunosenescence and inflamm aging as two sides of the same coin friends or foes
2018Co-Authors: Tamas Fulop, Anis Larbi, Gilles Dupuis, Aurelie Le Page, Eric Frost, Alan A Cohen, Jacek M Witkowski, Claudio FranceschiAbstract:The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed Immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, Immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of Immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the Immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
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intracellular signalling pathways targets to reverse Immunosenescence
2017Co-Authors: Tamas Fulop, Graham Pawelec, Carl Fortin, Jacek M Witkowski, Le A Page, Anis LarbiAbstract:Ageing is a very complex process, the result of the dysregulation of multiple systems interacting in many ways. A prominent change occurring with ageing is related to the architecture and functioning of the immune system, viewed commonly as detrimental and termed 'Immunosenescence'. However, age-associated changes may also lead to increased function in certain respects, which can be viewed as adaptive. None the less, on balance it is well-recognized that Immunosenescence is accompanied by the low-grade inflammation observed commonly in elderly people, which has been dubbed 'inflamm-ageing'. The exact cause and significance of all these changes is not clear, but there is a consensus that they are related to the occurrence of chronic non-infectious age-associated disease, as well as increased susceptibility to infections. Alterations to immune cell signalling may be a prominent cause of malfunctioning immunity. Emerging attempts to reverse Immunosenescence have recently targeted the signalling pathways in various different cell types of the immune system. Here, we review and discuss alterations in the signalling pathways of immune cells with ageing and consider current targets and means to modulate altered functions. We discuss the potential dangers as well as the benefits of these interventions, and consider future approaches to this problem.
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the role of Immunosenescence in the development of age related diseases
2016Co-Authors: Tamas Fulop, Gilles Dupuis, Jacek M Witkowski, Anis LarbiAbstract:Aging is a complex phenomenon leading to numerous changes in the physiological systems of the body. One of the most important changes, called Immunosenescence, occurs in the immune system. Immunosenescence covers changes in the innate and the adaptive immune systems and is associated with a low-grade inflammation called inflammaging. Aging, likely via inflammaging, is also associated with the emergence of chronic diseases including cardiovascular and neurodegenerative diseases, cancer, and diabetes mellitus type 2. The origin of this inflammaging is not known with certainty, but several concurrent contributing factors have been suggested, such as aging-associated changes in the innate and adaptive immune response, chronic antigenic stimulation, the appearance of endogenous macromolecular changes, and the presence of senescent cells exhibiting a senescence-associated secretory phenotype. A better understanding of the multiple biological phenomena leading to these diseases via the Immunosenescence associated with inflammaging provides a powerful target for interventions to increase the healthspan of elderly subjects.
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frailty inflammation and Immunosenescence
2015Co-Authors: Tamas Fulop, Graham Pawelec, Gilles Dupuis, Alan A Cohen, Jacek M Witkowski, Janet E Mcelhaney, Jose A Morais, Sarra Baehl, Xavier Camous, Anis LarbiAbstract:Frailty is a still-evolving concept of a complex phenomenon. There are several algorithms and strategies for assessing frailty syndrome, but currently, no universally accepted definition or measurement protocol has been determined. Consequently, the biological cause(s) of frailty are also poorly defined. Much circumstantial experimental data point to the dysregulation of several key physiological systems, including the neuroendocrine, musculoskeletal, metabolic and immune/inflammatory systems, resulting from alterations in functional reserves. Immune dysregulation and inflammation as causes of frailty have gained some support from the results of longitudinal studies, but a true causal relationship has not been established. This chapter will describe the immune/inflammatory alterations found in frailty and their putative causal relationships with this state.
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cellular signaling in the aging immune system
2014Co-Authors: Tamas Fulop, Carl Fortin, Gilles Dupuis, Aurelie Le Page, Jacek M Witkowski, Anis LarbiAbstract:Causes for Immunosenescence and inflamm-aging have to be established. Efficient function of the immune system requires homeostatic regulation from receptor recognition of antigenic challenge to cell responses and adaptation to its changing environment. It is reasonable to assume that one of the most important molecular causes of Immunosenescence is alteration in the regulation of signaling pathways. Indeed, alterations in feed-forward and negative feedback (inhibitory) signaling have been highlighted in all cells involved in the immune response including short-lived (neutrophils) and long-lived (T lymphocytes) cells. These dysregulations tip the balance in favor of altered (less efficient) function of the immune system. In this review, we summarize our knowledge on signal transduction changes in the aging immune system and propose a unifying mechanism as one of the causes of Immunosenescence. Modulation of these pathways with aging represents a major challenge to restore the immune response to functional levels.
Claudio Franceschi - One of the best experts on this subject based on the ideXlab platform.
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Immunosenescence and inflamm aging as two sides of the same coin friends or foes
2018Co-Authors: Tamas Fulop, Anis Larbi, Gilles Dupuis, Aurelie Le Page, Eric Frost, Alan A Cohen, Jacek M Witkowski, Claudio FranceschiAbstract:The immune system is the most important protective physiological system of the organism. It has many connections with other systems and is, in fact, often considered as part of the larger neuro-endocrine-immune axis. Most experimental data on immune changes with aging show a decline in many immune parameters when compared to young healthy subjects. The bulk of these changes is termed Immunosenescence. Immunosenescence has been considered for some time as detrimental because it often leads to subclinical accumulation of pro-inflammatory factors and inflamm-aging. Together, Immunosenescence and inflamm-aging are suggested to stand at the origin of most of the diseases of the elderly, such as infections, cancer, autoimmune disorders, and chronic inflammatory diseases. However, an increasing number of immune-gerontologists have challenged this negative interpretation of Immunosenescence with respect to its significance in aging-related alterations of the immune system. If one considers these changes from an evolutionary perspective, they can be viewed preferably as adaptive or remodeling rather than solely detrimental. Whereas it is conceivable that global immune changes may lead to various diseases, it is also obvious that these changes may be needed for extended survival/longevity. Recent cumulative data suggest that, without the existence of the Immunosenescence/inflamm-aging duo (representing two sides of the same phenomenon), human longevity would be greatly shortened. This review summarizes recent data on the dynamic reassessment of immune changes with aging. Accordingly, attempts to intervene on the aging immune system by targeting its rejuvenation, it may be more suitable to aim to maintain general homeostasis and function by appropriately improving immune-inflammatory-functions.
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report from the second cytomegalovirus and Immunosenescence workshop
2011Co-Authors: Mark R Wills, Calogero Caruso, Arne N Akbar, Mark Beswick, Jos A Bosch, Claudio Franceschi, Giuseppina Colonnaromano, Ambarish Dutta, Tamas FulopAbstract:The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and Immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.
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Immunosenescence and immunogenetics of human longevity
2008Co-Authors: Rita Ostan, Miriam Capri, Daniela Monti, Maria Scurti, Laura Bucci, Stefano Salvioli, Elisa Pini, Claudio FranceschiAbstract:At present, individuals can live up to 80–120 years, a time much longer than that of our ancestors, as a consequence of the improvements in life conditions and medical care. Thus, the human immune sys
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inflammaging and anti inflammaging a systemic perspective on aging and longevity emerged from studies in humans
2007Co-Authors: Claudio Franceschi, Miriam Capri, Daniela Monti, Sergio Giunta, Fabiola Olivieri, Federica Sevini, Maria Panagiota Panourgia, Laura Invidia, Laura Celani, Maria ScurtiAbstract:A large part of the aging phenotype, including Immunosenescence, is explained by an imbalance between inflammatory and anti-inflammatory networks, which results in the low grade chronic pro-inflammatory status we proposed to call inflammaging. Within this perspective, healthy aging and longevity are likely the result not only of a lower propensity to mount inflammatory responses but also of efficient anti-inflammatory networks, which in normal aging fail to fully neutralize the inflammatory processes consequent to the lifelong antigenic burden and exposure to damaging agents. Such a global imbalance can be a major driving force for frailty and common age-related pathologies, and should be addressed and studied within an evolutionary-based systems biology perspective. Evidence in favor of this conceptualization largely derives from studies in humans. We thus propose that inflammaging can be flanked by anti-inflammaging as major determinants not only of Immunosenescence but eventually of global aging and longevity.
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inflamm aging an evolutionary perspective on Immunosenescence
2006Co-Authors: Claudio Franceschi, Silvana Valensin, Massimiliano Bonafe, Fabiola Olivieri, Maria De Luca, Enzo Ottaviani, Giovanna De BenedictisAbstract:Abstract: In this paper we extend the “network theory of aging,” and we argue that a global reduction in the capacity to cope with a variety of stressors and a concomitant progressive increase in proinflammatory status are major characteristics of the aging process. This phenomenon, which we will refer to as “inflamm-aging,” is provoked by a continuous antigenic load and stress. On the basis of evolutionary studies, we also argue that the immune and the stress responses are equivalent and that antigens are nothing other than particular types of stressors. We also propose to return macrophage to its rightful place as central actor not only in the inflammatory response and immunity, but also in the stress response. The rate of reaching the threshold of proinflammatory status over which diseases/disabilities ensue and the individual capacity to cope with and adapt to stressors are assumed to be complex traits with a genetic component. Finally, we argue that the persistence of inflammatory stimuli over time represents the biologic background (first hit) favoring the susceptibility to age-related diseases/disabilities. A second hit (absence of robust gene variants and/or presence of frail gene variants) is likely necessary to develop overt organ-specific age-related diseases having an inflammatory pathogenesis, such as atherosclerosis, Alzheimer's disease, osteoporosis, and diabetes. Following this perspective, several paradoxes of healthy centenarians (increase of plasma levels of inflammatory cytokines, acute phase proteins, and coagulation factors) are illustrated and explained. In conclusion, the beneficial effects of inflammation devoted to the neutralization of dangerous/harmful agents early in life and in adulthood become detrimental late in life in a period largely not foreseen by evolution, according to the antagonistic pleiotropy theory of aging.
Calogero Caruso - One of the best experts on this subject based on the ideXlab platform.
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A novel B cell population revealed by a CD38/CD24 gating strategy: CD38 − CD24 − B cells in centenarian offspring and elderly people
2020Co-Authors: Silvio Buffa, Graham Pawelec, Calogero Caruso, Matteo Bulati, Mariavaleria Pellicano, Adriana Martorana, David Goldeck, Giuseppina Colonna-romanoAbstract:Abstract The B cell arm of adaptive immunity undergoes significant modifications with age. Elderly people are characterized by impaired B cell responses reflected in a reduced ability to effectively respond against viruses and bacteria. Alterations of immunity with advancing age (Immunosenescence) have been widely studied in centenarians who are considered a good example of successful aging. In recent years, attention has shifted to centenarian offspring (CO) as a model of people genetically advantaged for healthy aging and longevity. Here, we describe the preliminary characterization of a proposed new population of memory B cells, defined as CD19 , which we find at higher frequencies in the elderly but less so in CO than healthy age-matched random controls. In addition, we found a decreased expression of RP105 (CD180), a toll-like receptor-associated molecule, on these cells. CD180 downregulation may potentially be a marker of Immunosenescence. Moreover, we show that these CD19 + CD38
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Innate and Adaptive Immunity in Aging and Longevity: The Foundation of Resilience
2020Co-Authors: Alexey Moskalev, Ilia Stambler, Calogero CarusoAbstract:The interrelation of the processes of immunity and senescence now receives an unprecedented emphasis during the COVID-19 pandemic, which brings to the fore the critical need to combat Immunosenescence and improve the immune function and resilience of older persons. Here we review the historical origins and the current state of the science of innate and adaptive immunity in aging and longevity. From the modern point of view, innate and adaptive immunity are not only affected by aging but also are important parts of its underlying mechanisms. Excessive levels or activity of antimicrobial peptides, C-reactive protein, complement system, TLR/NF-\u3baB, cGAS/STING/IFN 1,3 and AGEs/RAGE pathways, myeloid cells and NLRP3 inflammasome, declined levels of NK cells in innate immunity, thymus involution and decreased amount of naive T-cells in adaptive immunity, are biomarkers of aging and predisposition factors for cellular senescence and aging-related pathologies. Long-living species, human centenarians, and women are characterized by less inflamm-aging and decelerated Immunosenescence. Despite recent progress in understanding, the harmonious theory of Immunosenescence is still developing. Geroprotectors targeting these mechanisms are just emerging and are comprehensively discussed in this article
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Immunosenescence and its hallmarks how to oppose aging strategically a review of potential options for therapeutic intervention
2019Co-Authors: Anna Aiello, Farzin Farzaneh, Giuseppina Candore, Calogero Caruso, Sergio Davinelli, Caterina Maria Gambino, Mattia Emanuela Ligotti, Nahid Zareian, Giulia AccardiAbstract:Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naive cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of Immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the role of nutrition and of immunomodulation in Immunosenescence is discussed, due to the multifactorial influence on these hallmarks. The close connection between nutrition, intake of bioactive nutrients and supplements, immune function, and inflammation demonstrate the key role of dietary strategies as regulators of immune response and inflammatory status, hence as possible modulators of the rate of Immunosenescence. In addition, potential options for therapeutic intervention are clarified. In particular, the use of interleukin-7 as growth factor for naive T cells, the function of checkpoint inhibitors in improving T cell responses during aging and, the potential of drugs that inhibit mitogen-activated protein kinases and their interaction with nutrient signaling pathways are discussed. Finally, it is suggested that the inclusion of appropriate combinations of toll-like receptor agonists may enhance the efficacy of vaccination in older adults.
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report from the second cytomegalovirus and Immunosenescence workshop
2011Co-Authors: Mark R Wills, Calogero Caruso, Arne N Akbar, Mark Beswick, Jos A Bosch, Claudio Franceschi, Giuseppina Colonnaromano, Ambarish Dutta, Tamas FulopAbstract:The Second International Workshop on CMV & Immunosenescence was held in Cambridge, UK, 2-4th December, 2010. The presentations covered four separate sessions: cytomegalovirus and T cell phenotypes; T cell memory frequency, inflation and Immunosenescence; cytomegalovirus in aging, mortality and disease states; and the immunobiology of cytomegalovirus-specific T cells and effects of the virus on vaccination. This commentary summarizes the major findings of these presentations and references subsequently published work from the presenter laboratory where appropriate and draws together major themes that were subsequently discussed along with new areas of interest that were highlighted by this discussion.
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b cells and Immunosenescence a focus on igg igd cd27 dn b cells in aged humans
2011Co-Authors: Matteo Bulati, Giuseppina Candore, Calogero Caruso, Silvio Buffa, Deborah K Dunnwalters, Mariavaleria Pellicano, Giuseppina Colonna RomanoAbstract:Immunosenescence contributes to the decreased ability of the elderly to control infectious diseases, which is also reflected in their generally poor response to new antigens and vaccination. It is known that the T cell branch of the immune system is impaired in the elderly mainly due to expansion of memory/effector cells that renders the immune system less able to respond to new antigens. B lymphocytes are also impaired in the elderly in terms of their response to new antigens. In this paper we review recent work on B cell Immunosenescence focusing our attention on memory B cells and a subset of memory B cells (namely IgG(+)IgD(-)CD27(-)) that we have demonstrated is increased in healthy elderly.
