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1.
Rev Med Suisse ; 15(660): 1512-1515, 2019 Aug 28.
Artigo em Francês | MEDLINE | ID: mdl-31496176

RESUMO

The emergence of immunotherapy has generated great enthusiasm in oncology improving the prognosis of pathologies such as melanoma, lung cancer, kidney cancer, bladder and head and neck cancers. This enthusiasm concerns also older patients in view of the good tolerance of immunotherapy in young people. However, advanced age is linked to changes in the immune system, called immunosenescence, which could have a negative impact on the efficacy and toxicity of immunotherapy treatment. Knowledge in terms of efficacy and tolerance is limited for geriatric patients, few being included in clinical studies. This article summarizes the experience of immunotherapy in large clinical trials. It appears that the immune checkpoint inhibitors are effective and well tolerated in the elderly.


Assuntos
Imunoterapia , Neoplasias , Fatores Etários , Humanos , Tolerância Imunológica , Imunossenescência , Oncologia/tendências , Neoplasias/terapia
2.
Braz J Med Biol Res ; 52(9): e8392, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31411315

RESUMO

The term inflammaging is now widely used to designate the inflammatory process of natural aging. During this process, cytokine balance is altered, presumably due to the loss of homeostasis, thus contributing to a greater predisposition to disease and exacerbation of chronic diseases. The aim of the study was to analyze the relationship between pro-inflammatory markers and age in the natural aging process of healthy individuals. One hundred and ten subjects were divided into 5 groups according to age (22 subjects/group). Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were quantified using the ELISA method. High-sensitivity C-reactive protein (hsCRP) was analyzed by turbidimetry according to laboratory procedures. The main findings of this study were: a positive correlation between hsCRP and IL-6 as a function of age (110 subjects); women showed stronger correlations; the 51-60 age group had the highest values for hsCRP and IL-6; women presented higher values for hsCRP in the 51-60 age group and higher values for IL-6 in the 61-70 age group; and men showed higher values in the 51-60 age group for hsCRP and IL-6. In conclusion, the natural aging process increased IL-6 and hsCRP levels, which is consistent with the inflammaging theory; however, women presented stronger correlations compared to men (IL-6 and hsCRP) and the 51-60 age range seems to be a key point for these increases. These findings are important because they indicate that early preventive measures may minimize the increase in these inflammatory markers in natural human aging.


Assuntos
Envelhecimento/fisiologia , Imunossenescência/fisiologia , Inflamação/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/análise , Proteína C-Reativa/análise , Colesterol/sangue , Feminino , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Consumo de Oxigênio/fisiologia , Fatores Sexuais , Triglicerídeos/sangue , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
3.
Ecol Lett ; 22(10): 1709-1722, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31321874

RESUMO

Immunosenescence, the decline in immune defense with age, is an important mortality source in elderly humans but little is known of immunosenescence in wild animals. We systematically reviewed and meta-analysed evidence for age-related changes in immunity in captive and free-living populations of wild species (321 effect sizes in 62 studies across 44 species of mammals, birds and reptiles). As in humans, senescence was more evident in adaptive (acquired) than innate immune functions. Declines were evident for cell function (antibody response), the relative abundance of naïve immune cells and an in vivo measure of overall immune responsiveness (local response to phytohaemagglutinin injection). Inflammatory markers increased with age, similar to chronic inflammation associated with human immunosenescence. Comparisons across taxa and captive vs free-living animals were difficult due to lack of overlap in parameters and species measured. Most studies are cross-sectional, which yields biased estimates of age-effects when immune function co-varies with survival. We therefore suggest longitudinal sampling approaches, and highlight techniques from human cohort studies that can be incorporated into ecological research. We also identify avenues to address predictions from evolutionary theory and the contribution of immunosenescence to age-related increases in disease susceptibility and mortality.


Assuntos
Aves/fisiologia , Imunossenescência , Mamíferos/fisiologia , Répteis/fisiologia , Envelhecimento , Animais , Estudos Transversais , Inflamação
4.
Emerg Med Clin North Am ; 37(3): 569-581, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31262422

RESUMO

The emergency department resuscitation of the critically ill geriatric patient is challenging and can be fraught with peril. The anatomic and physiologic changes that occur with aging can significantly influence the recognition of critical illness and the logistics of resuscitation itself. This article discusses the relevant physiologic changes with aging, the effect of these changes on clinical manifestations of critical illness in older adults, and the core principles of resuscitation in this population, with specific attention to sepsis and trauma care. In addition, end-of-life care is also discussed.


Assuntos
Estado Terminal/terapia , Serviço Hospitalar de Emergência , Ressuscitação , Idoso , Fenômenos Fisiológicos Cardiovasculares , Disfunção Cognitiva/complicações , Medicina de Emergência , Fragilidade/complicações , Avaliação Geriátrica , Taxa de Filtração Glomerular , Humanos , Hipnóticos e Sedativos/uso terapêutico , Imunossenescência , Limitação da Mobilidade , Manejo da Dor , Farmacocinética , Exame Físico , Fenômenos Fisiológicos Respiratórios , Sepse/diagnóstico , Sepse/terapia , Assistência Terminal , Equilíbrio Hidroeletrolítico , Ferimentos e Lesões/complicações , Ferimentos e Lesões/terapia
5.
Einstein (Sao Paulo) ; 17(2): eRB4733, 2019 May 02.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31066797

RESUMO

Healthy aging is partly related to appropriate function of the immune system. As already reported, some changes in this system are observed, including reduced number and repertoire of T cells due to thymic involution, accumulation of memory T cells by chronic infections, homeostatic proliferation compensating for the number of naïve T cells, decreased proliferation of T cells against a stimulus, telomere shortening, replicative senescence of the T cells, and inflammaging, besides the accumulation of myeloid-derived suppressor cells. The purpose of this article is to clarify each of these changes, aiming to minimize limitations of immunosenescence. If such associations can be established, these cells may be used as early and less invasive markers of aging-related diseases, as well as to indicate interventions, evaluate the efficacy of interventions and be a tool to achieve longevity with quality of life.


Assuntos
Envelhecimento/imunologia , Imunossenescência/imunologia , Células Supressoras Mieloides/fisiologia , Linfócitos T/fisiologia , Adaptação Fisiológica/imunologia , Proliferação de Células/fisiologia , Humanos
6.
Yonsei Med J ; 60(5): 407-413, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31016901

RESUMO

Although chronic obstructive pulmonary disease (COPD) is regarded as a chronic inflammatory lung disease, the disease mechanism is still not known. Intriguingly, aging lungs are quite similar to COPD-affected lungs in many ways, and COPD has been viewed as a disease of accelerated premature aging of the lungs. In this paper, based on a literature review, we would like to propose immunosenescence, age-associated decline in immunity, as a critical mechanism for the development of COPD. Immunosenescence can cause a low-grade, systemic inflammation described as inflammaging. This inflammaging may be directly involved in the COPD pathogenesis. The potential contributors to the development of inflammaging in the lungs possibly leading to COPD are discussed in the review paper. A notable fact about COPD is that only 15% to 20% of smokers develop clinically significant COPD. Given that there is a substantial inter-individual variation in inflammaging susceptibility, which is genetically determined and significantly affected by the history of the individual's exposure to pathogens, immunosenescence and inflammaging may also provide the answer for this unexpectedly low susceptibility of smokers to clinically significant COPD.


Assuntos
Imunossenescência , Doença Pulmonar Obstrutiva Crônica/imunologia , Envelhecimento/patologia , Humanos , Inflamação/patologia , Pulmão/patologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia
7.
Nat Med ; 25(3): 487-495, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30842675

RESUMO

Immune responses generally decline with age. However, the dynamics of this process at the individual level have not been characterized, hindering quantification of an individual's immune age. Here, we use multiple 'omics' technologies to capture population- and individual-level changes in the human immune system of 135 healthy adult individuals of different ages sampled longitudinally over a nine-year period. We observed high inter-individual variability in the rates of change of cellular frequencies that was dictated by their baseline values, allowing identification of steady-state levels toward which a cell subset converged and the ordered convergence of multiple cell subsets toward an older adult homeostasis. These data form a high-dimensional trajectory of immune aging (IMM-AGE) that describes a person's immune status better than chronological age. We show that the IMM-AGE score predicted all-cause mortality beyond well-established risk factors in the Framingham Heart Study, establishing its potential use in clinics for identification of patients at risk.


Assuntos
Citocinas/imunologia , Voluntários Saudáveis , Imunossenescência/imunologia , Linfócitos/imunologia , Mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Envelhecimento/imunologia , Feminino , Humanos , Individualidade , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fenótipo , Modelos de Riscos Proporcionais , Adulto Jovem
8.
Exerc Immunol Rev ; 25: 20-33, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30753128

RESUMO

Physical inactivity is one of the leading contributors to worldwide morbidity and mortality. The elderly are particularly susceptible since the features of physical inactivity overlap with the outcomes of natural aging - including the propensity to develop cardiovascular diseases, cancer, diabetes mellitus, sarcopenia and cognitive impairment. The age-dependent loss of immune function, or immunosenescence, refers to the progressive depletion of primary immune resources and is linked to the development of many of these conditions. Immunosenescence is primarily driven by chronic immune activation and physical activity interventions have demonstrated the potential to reduce the risk of complications in the elderly by modulating inflammation and augmenting the immune system. Since poor vaccination outcome is a hallmark of immunosenescence, the assessment of vaccine efficacy provides a window to study the immunological effects of regular physical activity. Using an accelerator-based study, we demonstrate in a Singaporean Chinese cohort that elderly women (n=56) who walk more after vaccination display greater post-vaccination expansion of monocytes and plasmablasts in peripheral blood. Active elderly female participants also demonstrated lower baseline levels of IP-10 and Eotaxin, and the upregulation of genes associated with monocyte/macrophage phagocytosis. We further describe postive correlations between the monocyte response and the post-vaccination H1N1 HAI titres of participants. Finally, active elderly women reveal a higher induction of antibodies against Flu B in their 18-month second vaccination follow-up. Altogether, our data are consistent with better immunological outcomes in those who are more physically active and highlight the pertinent contribution of monocyte activity.


Assuntos
Exercício , Imunossenescência , Vacinas contra Influenza/imunologia , Acelerometria , Idoso , Anticorpos Antivirais/sangue , Feminino , Humanos , Sistema Imunitário , Imunogenicidade da Vacina , Vírus da Influenza A Subtipo H1N1 , Influenza Humana/prevenção & controle , Monócitos/imunologia
9.
Int J Mol Sci ; 20(3)2019 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-30759732

RESUMO

Oxidative and inflammatory stresses are closely related processes, which contribute to age-associated impairments that affect the regulatory systems such as the immune system and its immunosenescence. Therefore, the aim of this work was to confirm whether an oxidative/inflammatory stress occurs in immune cells from adult mice with premature aging, similar to that shown in leukocytes from chronologically old animals, and if this results in immunosenescence. Several oxidants/antioxidants and inflammatory/anti-inflammatory cytokines were analyzed in peritoneal leukocytes from adult female CD1 mice in two models of premature aging-(a) prematurely aging mice (PAM) and (b) mice with the deletion of a single allele (hemi-zygotic: HZ) of the tyrosine hydroxylase (th) gene (TH-HZ), together with cells from chronologically old animals. Several immune function parameters were also studied in peritoneal phagocytes and lymphocytes. The same oxidants and antioxidants were also analyzed in spleen and thymus leukocytes. The results showed that the immune cells of PAM and TH-HZ mice presented lower values of antioxidant defenses and higher values of oxidants/pro-inflammatory cytokines than cells from corresponding controls, and similar to those in cells from old animals. Moreover, premature immunosenescence in peritoneal leukocytes from both PAM and TH-HZ mice was also observed. In conclusion, adult PAM and TH-HZ mice showed oxidative stress in their immune cells, which would explain their immunosenescence.


Assuntos
Senilidade Prematura/imunologia , Inflamação/imunologia , Estresse Oxidativo/imunologia , Senilidade Prematura/metabolismo , Animais , Antioxidantes/metabolismo , Modelos Animais de Doenças , Feminino , Imunossenescência/imunologia , Leucócitos/imunologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fagócitos/imunologia , Fagocitose/imunologia
10.
Cell Mol Life Sci ; 76(10): 1901-1918, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30788516

RESUMO

The aging process is associated with chronic low-grade inflammation in both humans and rodents, commonly called inflammaging. At the same time, there is a gradual decline in the functional capacity of adaptive and innate immune systems, i.e., immunosenescence, a process not only linked to the aging process, but also encountered in several pathological conditions involving chronic inflammation. The hallmarks of immunosenescence include a decline in the numbers of naïve CD4+ and CD8+ T cells, an imbalance in the T cell subsets, and a decrease in T cell receptor (TCR) repertoire and signaling. Correspondingly, there is a decline in B cell lymphopoiesis and a reduction in antibody production. The age-related changes are not as profound in innate immunity as they are in adaptive immunity. However, there are distinct functional deficiencies in dendritic cells, natural killer cells, and monocytes/macrophages with aging. Interestingly, the immunosuppression induced by myeloid-derived suppressor cells (MDSC) in diverse inflammatory conditions also targets mainly the T and B cell compartments, i.e., inducing very similar alterations to those present in immunosenescence. Here, we will compare the immune profiles induced by immunosenescence and the MDSC-driven immunosuppression. Given that the appearance of MDSCs significantly increases with aging and MDSCs are the enhancers of other immunosuppressive cells, e.g., regulatory T cells (Tregs) and B cells (Bregs), it seems likely that MDSCs might remodel the immune system, thus preventing excessive inflammation with aging. We propose that MDSCs are potent inducers of immunosenescence.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Imunossenescência/imunologia , Células Supressoras Mieloides/imunologia , Animais , Linfócitos B/imunologia , Linfócitos B/metabolismo , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Humanos , Células Supressoras Mieloides/metabolismo , Mielopoese/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , Receptores de Antígenos de Linfócitos T/metabolismo , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo
11.
Ann Diagn Pathol ; 38: 99-105, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30572149

RESUMO

T cell lymphoproliferative disorders that arise in the skin are mainly derived from post thymic T cells most commonly of CD4 subset. Human CD4 positive T cells are dynamic exhibiting phenotypic and functional malleability. For example, with repetitive antigen exposure most commonly associated with age, CD4 positive T cells acquire a cytotoxic phenotype. The authors present four cases characterized by cutaneous infiltrates of cytotoxic CD30 negative CD4 positive T cells in the skin; three cases were forms of malignant lymphoma other than mycosis fungoides and one case was a reactive lymphomatoid photodermatosis associated with underlying collagen vascular disease. The three patients with lymphoma were adult men, two above 50 years of age and all with disseminated cutaneous disease. One of these patients whose biopsy showed a large cell morphology succumbed to the disease while one patient with localized disease responded to local radiation. In all three cases there was a nodular and diffuse pan-dermal infiltrate which was predominated by non-cerebriform atypical lymphocytes ranging from small to intermediate sized cells in two cases to a large cell dominant morphology in one case. The biopsies showed some degree of epidermotropism, and in one case it was striking. Neoplastic cells were positive for CD4, and at least one cytotoxic protein (i.e. granzyme and/or TIA). CD56, CD57 or CD30 were negative. In addition, CD28, the naïve T cell marker, was negative. Based on the few cases reported herein, one might suggest that the prognosis mirrors that seen in other forms of cutaneous T cell lymphoma with mature small cell dominant infiltrates exhibiting an indolent pattern while a CD30 negative large cell T cell lymphoma would be expected to demonstrate an aggressive clinical course.


Assuntos
Linfócitos T CD4-Positivos/patologia , Imunossenescência , Linfoma Cutâneo de Células T/patologia , Neoplasias Cutâneas/patologia , Linfócitos T Citotóxicos/patologia , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem
12.
Nat Commun ; 9(1): 5435, 2018 12 21.
Artigo em Inglês | MEDLINE | ID: mdl-30575733

RESUMO

Cellular senescence is a stress response that imposes stable cell-cycle arrest in damaged cells, preventing their propagation in tissues. However, senescent cells accumulate in tissues in advanced age, where they might promote tissue degeneration and malignant transformation. The extent of immune-system involvement in regulating age-related accumulation of senescent cells, and its consequences, are unknown. Here we show that Prf1-/- mice with impaired cell cytotoxicity exhibit both higher senescent-cell tissue burden and chronic inflammation. They suffer from multiple age-related disorders and lower survival. Strikingly, pharmacological elimination of senescent-cells by ABT-737 partially alleviates accelerated aging phenotype in these mice. In LMNA+/G609G progeroid mice, impaired cell cytotoxicity further promotes senescent-cell accumulation and shortens lifespan. ABT-737 administration during the second half of life of these progeroid mice abrogates senescence signature and increases median survival. Our findings shed new light on mechanisms governing senescent-cell presence in aging, and could motivate new strategies for regenerative medicine.


Assuntos
Senescência Celular , Imunossenescência , Perforina/fisiologia , Animais , Compostos de Bifenilo/farmacologia , Compostos de Bifenilo/uso terapêutico , Avaliação Pré-Clínica de Medicamentos , Feminino , Inflamação/etiologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nitrofenóis/farmacologia , Nitrofenóis/uso terapêutico , Piperazinas/farmacologia , Piperazinas/uso terapêutico , Progéria/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Sulfonamidas/farmacologia , Sulfonamidas/uso terapêutico
13.
Semin Oncol ; 45(4): 187-200, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30539714

RESUMO

The advent of immune checkpoint inhibitors (ICIs) has changed the landscape of cancer treatment. Older adults represent the majority of cancer patients; however, direct data evaluating ICIs in this patient population is lacking. Aging is associated with changes in the immune system known as "immunosenescence" that could impact the efficacy and safety profile of ICIs. In this paper, we review aging-associated changes in the immune system as they may relate to cancer and immunotherapy, with mention of the effect of chronic viral infections and frailty. Furthermore, we summarize the current clinical evidence of ICI effectiveness and toxicity among older adults with cancer.


Assuntos
Envelhecimento/imunologia , Imunossenescência/imunologia , Imunoterapia , Animais , Humanos
14.
Rev. clín. esp. (Ed. impr.) ; 218(8): 426-434, nov. 2018. tab
Artigo em Espanhol | IBECS | ID: ibc-176236

RESUMO

La mejora de las condiciones de vida y los avances de la medicina han prolongado la esperanza y la calidad de vida, de tal forma que cada vez es mayor el número de viajeros de avanzada edad. Los cambios fisiopatológicos o los tratamientos pueden reducir la eficacia de las vacunas o facilitar interacciones medicamentosas. El viajero mayor presenta una serie de particularidades que se deben tener en cuenta a la hora de ofrecer un buen consejo pre-viaje. Esto debe incluir un correcto manejo de sus enfermedades crónicas susceptibles de agravarse durante el viaje, así como un adecuado estudio y seguimiento después del mismo. Se ha realizado una revisión narrativa de los principales problemas del viajero mayor


Improved living conditions and advances in medicine have extended life expectancy and quality of life, resulting in an increasing number of elderly travellers. Pathophysiological changes and treatments can reduce the efficacy of vaccines and facilitate drug interactions. Elderly travellers have various characteristics that should be considered when offering pre-trip counselling, which should include proper management of chronic diseases that are susceptible to worsening during the trip, as well as an appropriate study and follow-up after the trip. We performed a narrative review of the main problems of elderly travellers


Assuntos
Humanos , Idoso , Saúde do Viajante , Controle Sanitário de Viajantes , Múltiplas Afecções Crônicas/epidemiologia , Interações de Medicamentos , Imunossenescência/fisiologia , Envelhecimento/fisiologia , Vacinação
15.
Rev. esp. geriatr. gerontol. (Ed. impr.) ; 53(supl.2): 185-202, sept. 2018. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-178172

RESUMO

La gripe es un importante problema de salud pública, particularmente en las personas susceptibles de presentar complicaciones asociadas, personas mayores, niños menores de 2 años, enfermos crónicos, inmunocomprometidos y embarazadas. Pero, además, la gripe tiene un gran impacto sanitario con un aumento de la demanda asistencial y un espectacular aumento de las visitas ambulatorias, sobrecargando los servicios de urgencias y hospitalarios. Durante los brotes epidémicos, las tasas de hospitalización de las personas mayores de 65 años son máximas y la mortalidad notificada por gripe en la temporada 2017/2018 ha sido de 960 defunciones. La vacunación antigripal estacional es el método con una mayor relación coste-efectividad de prevención primaria de la gripe, reduciendo las enfermedades respiratorias relacionadas, el número de visitas a las consultas médicas, el número de hospitalizaciones y muertes en personas de alto riesgo y el absentismo laboral en adultos. En los últimos años la gripe B ha recibido escasa atención en la literatura científica y, sin embargo, en períodos interepidémicos, la gripe B puede ser una de las principales causas de epidemias de gripe estacional, causando una considerable morbimortalidad y un aumento de costes. La vacuna tetravalente, a diferencia de la trivalente, obtiene una protección inmunológica frente al segundo linaje de la gripe B y, de acuerdo con una revisión crítica de la literatura científica, proporciona una protección más amplia sin afectar a la inmunogenicidad de las otras 3 cepas vacunales comunes a las vacunas trivalente y tetravalente. La vacuna tetravalente es coste-efectiva al disminuir el número de casos de gripe y siempre es una intervención rentable, con un importante ahorro de coste para el sistema de salud y para la sociedad, disminuyendo las tasas de hospitalización y de mortalidad asociadas a las complicaciones de la gripe


Influenza is a significant health problem, particularly in those persons susceptible to having associated complications, older people, children less than 2 years, patients with chronic diseases, immunocompromised patients, and pregnant women. But influenza also has a large impact on the health system, with an increase in the healthcare demand and a spectacular increase in outpatient visits, overloading the emergency and hospital services. During epidemic outbreaks, the hospital admission rates of people over 65 years are at a maximum, and the mortality notified for the 2017/2018 influenza season was 960 deaths. The seasonal anti-influenza vaccine is the method with a better cost-effective ratio of primary prevention of influenza, reducing associated respiratory diseases, the number of hospital admissions, and deaths in high risk individuals, as well as work absenteeism in adults. In the last few years, influenza B has received little attention in the scientific literature, although in the periods between epidemics influenza B can be one of the main causes of seasonal epidemics, causing considerable morbidity and mortality and an increase in costs. The quadrivalent vaccine has a second-line immunological protection against influenza B, and according to a critical review of the scientific literature, it provides wider protection without affecting immunogenicity of the other three vaccine strains common to the trivalent and tetravalent vaccine. The quadrivalent vaccine is cost-effective in reducing the number of influenza cases, and is always a worthwhile intervention, with a significant cost saving for the health system and for society, by reducing the hospital admission rates and mortality associated with the complications of influenza


Assuntos
Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Vacinas contra Influenza/análise , Influenza Humana/prevenção & controle , Imunogenicidade da Vacina , Influenza Humana/epidemiologia , Análise Custo-Benefício , Imunossenescência/imunologia , Envelhecimento/imunologia , Efeitos Psicossociais da Doença , Espanha/epidemiologia , Vírus da Influenza A/patogenicidade , Influenzavirus A/patogenicidade , Vírus da Influenza B/patogenicidade , Influenzavirus B/patogenicidade , Vacinas Anti-Haemophilus/análise , Vigilância de Produtos Comercializados/tendências
16.
J Photochem Photobiol B ; 186: 69-80, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015062

RESUMO

The awareness of the interrelationship between immunosenescence and constant light exposure can provide new insights into the consequences of excessive exposure to light at night due to light pollution or shift work. Here, we investigated whether constant light exposure (LL) acts as an inducer of immunosenescence. We also determined the role of melatonin or turmeric in reversing the putative effects of constant light and explored for the first time the underlying molecular mechanisms. Young (3-4-month-old) rats were exposed daily to LL alone or in combination with each of melatonin and turmeric for 12 weeks. A group of aged rats (18-months old; n = 6) was used as a reference for natural immunosenescence. Constant light exposure resulted in remarkable pathophysiological alterations resembling those noticed in normal aged rats, manifested as apparent decreases in antioxidant activities as well as Nrf2 and DJ-1 expressions, striking augmentation in oxidative stress, proinflammatory cytokines and expression of TNFα, Bax, and p53 genes, and deleterious changes of lymphoid organs, Co-administration of melatonin or turmeric was able to reverse all alterations induced by LL through upregulation of Nrf2/DJ-1 and downregulation of p53/Bax pathways. These data suggest that LL accelerates immunosenescence via oxidative stress and apoptotic pathways. They also demonstrate for the first time that turmeric is comparable to melatonin in boosting the immune function and counteracting the LL-associated immunosenescence. These effects suggest that turmeric supplementation can be used as an inexpensive intervention to prevent circadian disruption-related immunosenescence. However, to validate the effects of turmeric on humans further studies are warranted.


Assuntos
Imunossenescência/efeitos dos fármacos , Luz , Melatonina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Animais , Antioxidantes/metabolismo , Ritmo Circadiano/efeitos dos fármacos , Ritmo Circadiano/efeitos da radiação , Citocinas/sangue , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/efeitos da radiação , Imunossenescência/efeitos da radiação , Masculino , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Oxirredutases/metabolismo , Proteína Desglicase DJ-1/genética , Proteína Desglicase DJ-1/metabolismo , Ratos , Transdução de Sinais/efeitos da radiação , Baço/efeitos dos fármacos , Baço/metabolismo , Baço/patologia , Timo/efeitos dos fármacos , Timo/metabolismo , Timo/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/efeitos da radiação , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
17.
J Altern Complement Med ; 24(7): 709-716, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29762043

RESUMO

OBJECTIVE: To explore the safety and efficacy of fish oil to modulate parameters of inflammation and immunosenescence in HIV-infected older adults. DESIGN: This study uses a randomized, controlled, double-blind clinical trial. SETTING: The study was conducted in an outpatient HIV/AIDS clinic in a large urban Midwestern city in the United States. SUBJECTS: A total of 37 clinically stable HIV-infected adults between the ages of 40 and 70 years of age participated. INTERVENTIONS: Fish oil 1.6 g/day was administered for 12 weeks or placebo. OUTCOME MEASURES: Inflammatory cytokine production, surface markers of immunosenescence, and adverse events were measured. RESULTS: After 12 weeks of supplementation, there were no significant differences between the treatment and control groups on any measures of inflammation or immunosenescence in both CD4+ and CD8+ T lymphocytes. More participants in the treatment group reported adverse gastrointestinal events compared with the control group. CONCLUSIONS: A 12-week supplementation regimen of 1.6 g/day of fish oil did not favorably modulate parameters of inflammation or immune senescence in HIV-infected adults. Future studies should test agents that directly target mechanisms that underlie HIV-related inflammation to determine whether reducing inflammation can reverse immunosenescence.


Assuntos
Citocinas/sangue , Óleos de Peixe , Infecções por HIV/complicações , Imunossenescência/efeitos dos fármacos , Inflamação , Biomarcadores/sangue , Suplementos Nutricionais , Método Duplo-Cego , Ácidos Graxos Ômega-3/administração & dosagem , Ácidos Graxos Ômega-3/farmacologia , Ácidos Graxos Ômega-3/uso terapêutico , Feminino , Óleos de Peixe/administração & dosagem , Óleos de Peixe/farmacologia , Óleos de Peixe/uso terapêutico , Humanos , Inflamação/sangue , Inflamação/tratamento farmacológico , Inflamação/etiologia , Masculino , Pessoa de Meia-Idade , Meio-Oeste dos Estados Unidos
18.
Mediators Inflamm ; 2018: 6039171, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29706800

RESUMO

Aging is characterized by the progressive decline of physiological function and tissue homeostasis leading to increased vulnerability, degeneration, and death. Aging-related changes of the innate and adaptive immune system include decline in the preservation and enhancement of many immune functions, such as changes in the number of circulating monocytic and dendritic cells, thymic involution, T cell polyfunctionality, or production of proinflammatory cytokines, and are defined as immunosenescence. Inflammatory functions are increased with age, causing the chronic low-grade inflammation, referred to as inflamm-aging, that contribute, together with immunosenescence, to neurodegenerative diseases. In this review, we discuss the link between the immune and nervous systems and how the immunosenescence and inflamm-aging can contribute to neurodegenerative diseases.


Assuntos
Imunossenescência/fisiologia , Doenças Neurodegenerativas/metabolismo , Animais , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Humanos , Imunidade Inata/imunologia , Doenças Neurodegenerativas/imunologia
19.
Bratisl Lek Listy ; 119(4): 217-220, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29663819

RESUMO

With ageing of their populations, many societies are challenged with serious systemic diseases. One of the causes of these diseases could be the age-related defects in immune system termed immunosenescence. Immunosenescence is characterized by accumulation of memory and non-functional immune cells, impaired signalling due to restricted repertoire of receptors, overall pro-inflammatory environment and complete dysregulation of the immune system. Consequences of immunosenescence are serious, older people are not able to respond to new stimuli, including infections and vaccinations and are more prone to oncologic, neurodegenerative and autoimmune diseases (Ref. 49).


Assuntos
Envelhecimento/imunologia , Doenças Autoimunes/imunologia , Imunossenescência/imunologia , Imunoterapia , Neoplasias/imunologia , Doenças Neurodegenerativas/imunologia , Humanos , Vacinação
20.
Respirology ; 23(6): 567-575, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29607596

RESUMO

With the ageing population globally, tuberculosis (TB) in older people becomes a major clinical and public health challenge. In many Asian countries, especially those located in the eastern and southeastern parts of the continent, geriatric TB is a significant problem. TB in the older patients is more difficult to diagnose in the early course of disease, and has poorer treatment outcomes, largely as increased failure and death. More drug-induced adverse reactions are also experienced by this population during TB therapy. Oxidative stress and mitochondrial dysfunction are now well recognized to be associated with the ageing process, and it is likely that the cellular and molecular perturbations interact inextricably with the immunological dysfunction biophysiologically inherent to ageing. These underlying mechanistic bases putatively contribute to the development of TB in the geriatric population and worsen the disease outcomes, especially when the TB is compounded by co-morbid conditions such as smoking and diabetes mellitus. Unravelling these mechanisms further would yield knowledge that might potentially help to prevent reactivated TB in older people, and also to better manage the established disease with drug regimens and other new therapeutic strategies. In addition, addressing the social elements associated with geriatric TB is also imperative in the relief of individual patient suffering and improvement of overall disease control.


Assuntos
Envelhecimento/imunologia , Diabetes Mellitus/epidemiologia , Fumar/epidemiologia , Tuberculose/epidemiologia , Idoso , Envelhecimento/metabolismo , Antituberculosos/uso terapêutico , Ásia/epidemiologia , Austrália/epidemiologia , Comorbidade , Humanos , Imunossenescência , Tuberculose Latente/tratamento farmacológico , Tuberculose Latente/epidemiologia , Tuberculose Latente/metabolismo , Mitocôndrias/metabolismo , Estresse Oxidativo/imunologia , Saúde Pública , Tuberculose/diagnóstico , Tuberculose/tratamento farmacológico , Tuberculose/imunologia , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/epidemiologia , Tuberculose Pulmonar/metabolismo
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