Reduced naïve T cell numbers correlate with increased low-grade systemic inflammation during ageing and can be modulated by physical activity / Un número reducido de células T vírgenes se correlaciona con un aumento de la inflamación sistémica de bajo grado durante el envejecimiento y puede ser modulado por la actividad física

SUMMARY: Age-associated decline of immune system, termed immunosenescence, is characterized by low-grade systemic inflammation, known as inflammaging, together with T-cell functional dysregulation. Although affecting all individuals, different environmental as well genetic factors impinge on the individual´s susceptibility or resilience to immunosenescence. Physical activity has been shown to improve autonomy and functionality in older adults. However, if physical activity affects immunosenescence or inflammaging remains unknown. The purpose of this study was to analyze immunosenescence and inflammaging in elderly individuals by measuring peripheral naïve T cells and interleukin (IL) -6 from peripheral blood and evaluate the impact of physical activity on T cell dysregulation and inflammaging. Thirty (30) elderly volunteers (10 males and 20 females), and 7 young controls (2 males ad 7 females), were recruited for this study. A methodology questionnaire was used to evaluate different parameters such as physical activity, and peripheral naïve CD4+ and CD8+ T cells and serum IL-6 were measured by FACS and ELISA respectively. Our results shown that naïve T cells decline, and IL-6 levels increase as older people age. Interestingly, we observed strong negative correlation between naïve T cells numbers and IL-6 levels in older adults, suggesting a direct link between reduced naïve T cell pool and increased inflammaging. Continuous physical activity during youth did not affect immunosenescence and inflammaging in elderly, but physical activity during elderly increase naïve T cell numbers and reduce inflammaging in older subjects. Our results showed reduced number of naïve T cells and increased levels of IL-6 as elder people get older. Moreover, the strong negative correlation between these parameters suggest that naïve T cells can have a direct suppressive activity over innate immune components. Furthermore, physical activity during elderly can reduce immunosenescence and inflammaging in older subjects.

RESUMEN: El deterioro del sistema inmunológico asociado con la edad, denominado inmunosenescencia, se caracteriza por una inflamación sistémica de bajo grado, conocida como inflamaging, junto con una desregulación funcional de las células T. Aunque afectan a todos los individuos, diferentes factores ambientales y genéticos inciden en la susceptibilidad o resiliencia del individuo a la inmunosenescencia. Estudios anteriores han demostrado que la actividad física mejora la autonomía y la funcionalidad en los adultos mayores, aunque como la actividad física impacta a la inmunosenescencia e inflammaging es aún desconocido. El propósito de este estudio fue analizar la inmunosenescencia e inflammaging en personas de edad avanzada, midiendo las células T vírgenes y la interleucina (IL)-6 de sangre periférica, junto con evaluar el impacto de la actividad física sobre la inflamación basal y la inmunosenescencia. Treinta voluntarios ancianos (10 hombres y 20 mujeres) y 7 controles jóvenes (2 hombres y 5 mujeres) fueron incluidos en este estudio. Para medir actividad física, autonomía y dependencia se utilizó un cuestionario de metodología, junto con evaluar el número de células T CD4+ y CD8+ periféricas vírgenes e IL-6 sérica mediante FACS y ELISA, respectivamente. Nuestros resultados muestran que las células T vírgenes disminuyen y los niveles de IL-6 aumentan a medida que las personas mayores envejecen. Curiosamente, observamos una fuerte correlación negativa entre el número de células T vírgenes y los niveles de IL-6 en adultos mayores, lo que sugiere un vínculo directo entre la reducción de la reserva de células T vírgenes y el aumento de la inflamación. La actividad física durante la juventud no afectó la inmunosenescencia ni la inflamación en los ancianos, pero la actividad física durante la vejez aumenta el número de células T vírgenes y reduce la inflamación en los adultos mayores. Estos resultados sugieren que inmunosenescencia e inflammaging parecen estar directamente conectados, además de concluir que el desarrollo de actividad física durante la vejez reduce la inmunosenescencia y la inflamación basal en adultos mayores.

A propósito del Covid-19. El rol de la edad y género en la inmunidad / About the Covid-19. The role of age and gender in immunity

The purpose of the immune system is to protect the body from pathogenic microorganisms such as bacteria, viruses, fungi and even tumor cells, which could cause disease. When the encounter with pathogens occurs, defenses are produced immediately through the innate response, faster and more nonspecific, and through the adaptive response, more defined and personalized for each attacker. Both are triggered by the cells of the immune system being able to communicate with each other, once they have been activated. The innate immune system works in tune with the acquired immune system through the close intervention of the sex hormones, with specific strategies of estrogen and progesterone. Both have a proven anti-inflammatory and antioxidant action not only at the level of the wall of blood vessels, skin and mucous membranes, but also in the protection of the central nervous system against all toxic agents, such as viruses. Estrogens and progesterone play an essential role in the immune response and its evolution, and although they initially appear as antagonistic responses, they are not, despite the fact that estrogens increase and progesterone seems to suppress the immune response, depending on the immune target according to the case. (AU)

Immunosenescence: participation of T lymphocytes and myeloid-derived suppressor cells in aging-related immune response changes / Imunosenescência: participação de linfócitos T e células mieloides supressoras nas alterações da resposta imune relacionadas ao envelhecimento

ABSTRACT 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.

RESUMO O envelhecimento saudável está relacionado, pelo menos em parte, com a função adequada do sistema imunológico. Isso porque já foi relatado que, com o envelhecimento, algumas mudanças desse sistema são observadas, como a diminuição da percentagem e do repertório de células T pela involução tímica, acúmulo de células T de memória por infecções crônicas, compensação do número de células T naïve por proliferação homeostática, diminuição da capacidade de proliferação das células T frente a um estímulo, encurtamento dos telômeros, senescência replicativa das células T, e inflammaging, além do acúmulo de células mieloides supressoras. Este artigo visa esclarecer cada uma das mudanças, mencionadas, com o intuito de buscar meios de minimizar as limitações da imunosenescência. Caso seja possível estabelecer tais relações, essas células podem ser utilizadas como marcadores precoces e pouco invasivos de doenças relacionadas ao envelhecimento, além da possibilidade de serem utilizadas para indicar intervenções, avaliar a eficácia das intervenções e como ferramenta para alcance da longevidade com qualidade de vida.

Time-course of health-related adaptations in response to combined training in hypertensive elderly: immune and autonomic modulation interactions

This article is a methodological description of a randomized clinical trial (ClinicalTrials.gov U1111-1181-4455) aiming to evaluate the time-course (monthly) and associations between blood pressure changes and other health-related adaptations in response to exercise training in hypertensive elderly. Methods: The patients will be randomized to a control or combined training group interventions (aerobic and resistance exercise), with monthly assessments in four months. Although, the changes in baseline blood pressure is the primary clinical outcome, the secondary outcomes include: body composition, cardiorespiratory fitness, muscle strength, arterial stiffness, baroreceptor sensitivity, cardiovascular autonomic modulation, inflammatory markers, oxidative stress, growth factors, tissue remodeling markers, metabolic profile, renal function, cognitive function and quality of life. Results: To support the understanding of the blood pressure changes in hypertensive elderly, a time-course of exercise-induced adaptations including cardiovascular and immunological adaptations are fundamental for research in this field. Conclusion: To investigate the time-course of combined training-induced adaptations including all the diverse aspects of health in hypertensive elderly a well-controlled protocol design is necessary, mainly to clarify the relationship between cardiovascular and immunological exercise-induced adaptations.(AU)

Abnormal phenotypic distribution of regulatory and effector T cells in octogenarian and nonagenarian women / Distribuição fenotípica anormal das células T reguladoras e efetoras em mulheres octogenárias e nonagenárias

SummaryIntroduction:aging is associated with several immunologic changes. Regulatory (Treg) and effector T cells are involved in the pathogenesis of infectious, neoplastic, and autoimmune diseases. Little is known about the effects of aging on the frequency and function of these T cell subpopulations.Methods:peripheral blood mononuclear cells (PBMC) were obtained from 26 young (under 44 years old) and 18 elderly (above 80 years old) healthy women. T cell subpopulations were analyzed by flow cytometry.Results:elderly individuals had lower frequency of several activated effector T cell phenotypes as compared with young individuals: CD3+CD4+CD25+ (3.82±1.93 versus 9.53±4.49; p<0.0001); CD3+CD4+CD25+CD127+(2.39±1.19 versus 7.26±3.84; p<0.0001); CD3+CD4+CD25+ (0.41±0.22 versus 1.86±0.85, p<0.0001); and CD3+CD4+CD25highCD127+(0.06±0.038 versus 0.94±0.64, p<0.0001). Treg (CD3+CD4+CD25+CD127øFoxp3+) presented lower frequency in elderly individuals as compared to young adults (0.34±0.18 versus 0.76±0.48; p=0.0004) and its frequency was inversely correlated with age in the whole group (r=-0.439; p=0.013). The elderly group showed higher frequency of two undefined CD25øFoxp3+ phenotypes: CD3+CD4+CD25øFoxp3+(15.05±7.34 versus 1.65±1.71; p<0.0001) and CD3+CD4+CD25øCD127øFoxp3+(13.0±5.52 versus 3.51±2.87; p<0.0001).Conclusions:the altered proportion of different T cell subsets herein documented in healthy elderly women may be relevant to the understanding of the immunologic behavior and disease susceptibility patterns observed in geriatric patients.

ResumoIntrodução:o envelhecimento está associado a diversas alterações imunológicas. Células T reguladoras e efetoras estão envolvidas na patogênese de enfermidades infecciosas, neoplásicas e autoimunes. Pouco se sabe acerca dos efeitos da idade sobre a frequência e a função dessas populações celulares.Métodos:células mononucleares do sangue periférico foram obtidas de participantes saudáveis (26 com idade inferior a 44 anos e 18 acima de 80 anos). As subpopulações celulares foram analisadas por citometria de fluxo.Resultados:o grupo constituído por idosas apresentou menor frequência de vários fenótipos de células T efetoras ativadas em comparação com jovens: CD3+CD4+CD25+ (3,82±1,93 versus 9,53±4,49, p<0,0001); CD3+CD4+ CD25+CD127+ (2,39±1,19 versus7,26±3,84, p<0,0001); CD3+CD4+CD25high(0,41±0,22 versus 1,86±0,85, p<0,0001); CD3+CD4+CD25highCD127+(0,06±0,038 versus 0,94±0,64, p<0,0001). As células T reguladoras CD3+CD4+CD25highCD127øFoxP3+ apresentaram menor frequência em indivíduos idosos em comparação com adultos jovens (0,34±0,18 versus0,76±0,48, p=0,0004) e sua frequência foi inversamente correlacionada com a idade em todo o grupo (r=-0,439; p=0,013). O grupo de idosas apresentou maior frequência de dois fenótipos indefinidos (CD25øFoxP3+), células CD3+CD4+CD25øFoxP3+ (15,05±7,34 versus 1,65±1,71, p<0,0001) e células CD3+CD4+CD25øCD127øFoxP3+(13,0±5,52 versus 3,51±2,87, p<0,0001).Conclusão:as proporções alteradas de diferentes subpopulações de células T em idosas saudáveis contribuem para a compreensão dos padrões de comportamento e suscetibilidade a doenças imunológicas evidenciadas em pacientes geriátricos.

Inmunosenescencia: efectos de la edad sobre el sistema inmune / Immunosenescence: effects of aging process on immune system

El proceso de envejecimiento provoca cambios en el sistema inmune que afectan su funcionamiento y desarrollo. Estos cambios pueden manifestarse desde la linfopoyesis hasta la respuesta que orquesta el sistema inmune frente a determinada enfermedad o agente infeccioso. Ambas ramas de la inmunidad, innata y adaptativa, se afectan en este proceso, lo que genera un impacto negativo en la respuesta inmune de los ancianos y los predispone a padecer enfermedades infecciosas, cáncer, autoinmunidad y a desarrollar respuestas pobres tras la administración de vacunas...

The aging process produces functional and developmental changes in the immune system. Those changes may appear from lymphopoiesis up to the final response of the immune system facing a certain disease. Both branches of immunity, innate and adaptive, are affected by the aging process; hence these changes can have a negative impact on the immune response of elderly patients and increase their susceptibility to infectious diseases, cancer and decreased vaccine efficacy...

Prevalencia y causas de ceguera en Perú: encuesta nacional / National survey on the prevalence and causes of blindness in Peru

OBJETIVO: Estimar la prevalencia de ceguera y deficiencia visual en adultos de Perú y precisar sus causas, evaluar la cobertura y la calidad de los servicios de cirugía de catarata y determinar las barreras que impiden acceder a esos servicios. MÉTODOS: Estudio poblacional transversal con muestreo aleatorio por conglomerado en dos pasos de personas de 50 años o más, representativo de todo el país, mediante la metodología estándar de la Evaluación Rápida de Ceguera Evitable. Se midió la agudeza visual y se examinó el cristalino y el polo posterior por oftalmoscopía directa. Se calculó la cobertura de cirugía de catarata y se evaluó su calidad, además de las causas de tener una agudeza visual < 20/60 y las barreras para acceder a ese tratamiento. RESULTADOS:Se examinaron 4 849 personas. La prevalencia de ceguera fue 2,0% (intervalo de confianza de 95%: 1,5-2,5%). La catarata fue la causa principal de ceguera (58,0%), seguida por el glaucoma (13,7%) y la degeneración macular relacionada con la edad (11,5%). Los errores de refracción no corregidos fueron la principal causa de deficiencia visual moderada (67,2%). La cobertura de cirugía de catarata fue de 66,9%, y 60,5% de los ojos operados de catarata logró una AV ≥ 20/60 con la corrección disponible. Las principales barreras para someterse a la cirugía de catarata fueron el alto costo (25,9%) y no saber que el tratamiento es posible (23,8%). CONCLUSIONES: La prevalencia de ceguera y deficiencia visual en Perú es similar a la de otros países latinoamericanos. La baja cobertura de cirugía de catarata y el envejecimiento poblacional indican que para aumentar el acceso a estos servicios se debe mejorar la educación de la población en salud ocular y la capacidad resolutiva de los servicios oftalmológicos y de cirugía de catarata, y reducir su costo.

OBJECTIVE: To estimate the prevalence of blindness and visual impairment among adults in Peru and to determine their causes, to evaluate the coverage and quality of the cataract surgical services and to investigate the barriers that inhibit access to these services. METHODS: A cross-sectional population study with two-stage random cluster sampling of individuals of ≥ 50 years old, representative of the entire country, using the standard methodology of the Rapid Assessment of Avoidable Blindness. Visual acuity was assessed and the condition of the lens and posterior pole examined by direct ophthalmoscopy. Cataract surgical coverage was calculated. Its quality, as well as the causes of visual acuity < 20/60 and the barriers to accessing surgical treatment were assessed. RESULTS: A total of 4 849 people were examined. Blindness prevalence was 2.0% (confidence interval of 95%: 1.5-2.5%). The main causes of blindness were cataract (58.0%), glaucoma (13.7%) and age-related macular degeneration (11.5%). Uncorrected refraction errors were the principal cause of moderate visual impairment (67.2%). Cataract surgical coverage was 66.9%. 60.5% of the eyes operated for cataracts achieved a visual acuity ≥ 20/60 with available correction. The main barriers to cataract surgery were the high cost (25.9%) and people being unaware that treatment was possible (23.8%). CONCLUSIONS: The prevalence of blindness and visual impairment in Peru is similar to that of other Latin American countries. Given the low cataract surgical coverage and the aging of the population, access to the services could be improved by increasing the population education on eye health and the response capacity of the ophthalmological and cataract surgical services, and by reducing the costs of the latter.

Age-Related CD4+CD25+Foxp3+ Regulatory T-Cell Responses During Plasmodium berghei ANKA Infection in Mice Susceptible or Resistant to Cerebral Malaria

Different functions have been attributed to CD4+CD25+Foxp3+ regulatory T-cells (Tregs) during malaria infection. Herein, we describe the disparity in Treg response and pro- and anti-inflammatory cytokines during infection with Plasmodium berghei ANKA between young (3-week-old) and middle-aged (8-month-old) C57BL/6 mice. Young mice were susceptible to cerebral malaria (CM), while the middle-aged mice were resistant to CM and succumbed to hyperparasitemia and severe anemia. The levels of pro-inflammatory cytokines, such as TNF-alpha, in young CM-susceptible mice were markedly higher than in middle-aged CM-resistant mice. An increased absolute number of Tregs 3-5 days post-inoculation, co-occurring with elevated IL-10 levels, was observed in middle-aged CM-resistant mice but not in young CM-susceptible mice. Our findings suggest that Treg proliferation might be associated with the suppression of excessive pro-inflammatory Th1 response during early malaria infection, leading to resistance to CM in the middle-aged mice, possibly in an IL-10-dependent manner.

Estudo longitudinal do nível de atividade física de mulheres idosas / Longitudinal study of physical activity level of older adult women

O objetivo deste estudo foi analisar as alterações longitudinais no nível de atividade física (NAF) de mulheres idosas. Este estudo longitudinal conduziu a primeira avaliação em 2005 e 2006, e a segunda avaliação em 2011, na qual participaram 78 mulheres (73,2±5,2 anos). O NAF foi avaliado através do Modified Baecke Questionnaire for Older Adults, o qual inclui os domínios: doméstico, esportivo e recreativo. A descrição da amostra foi realizada pela média e desvio padrão. A análise dos dados foi realizada por uma MANOVA e do teste multivariado de Hotelling?s trace afim de verificar o efeito do tempo sobre os domínios do NAF (p<0,05). O teste multivariado de Hotelling?s trace indicou diferenças significativas da variável independente (efeito do tempo: avaliações 1 e 2) (F1,154=2,923; p=0,036), para o NAF total (F1,154=5,449; p=0,021), e domínios doméstico (F1,154=4,325; p=0,039) e recreativo (F1,154=5,299; p=0,023). O NAF total alterou em -16,7%, NAF doméstico em -7,6%, NAF recreativo em -48,6% (todos com p<0,05); e o NAF esportivo declinou 12,0% (F1,154 = 0,892; p=0,346). Concomitantemente ao avanço da idade, ocorre um declínio nos domínios do NAF de idosas, seja em atividades relacionadas ao cuidado da residência, exercícios físicos, ou atividades recreativas. Esses resultados demonstram a necessidade de maximizar politicas públicas para o cuidado à saúde do idoso a fim de promover atividades físicas nos diferentes domínios, e motivar idosos a manterem uma vida ativa e independente, principalmente participando regularmente de um programa de exercícios físicos, beneficiando a qualidade e os anos adicionais de vida e desta população.

The aim of this study was to analyze longitudinal changes on physical activity level (PAL) of older adult women. This longitudinal study conducted the first evaluation on 2005 and 2006, and the second evaluation on 2011, in which 78 older women (73.2±5.2 yrs) participated in the follow-up evaluation. PAL was evaluated by the Modified Baecke Questionnaire for Older Adults, which includes the domestic, sportive and recreational domains. Data was described by mean and standard deviation, and was analyzed by using a MANOVA and the Hotelling?s trace multivariate test with the purpose to verify a time main effect on PAL domains (p<0.05). The multivariate test indicated significant differences for the independent variables (time effect: baseline and follow-up evaluations; F1,154=2,923; p=0.036) for PAL-total (F1,154=5,449; p=0.021), PAL-domestic (F1,154=4,325; p=0.039) and PAL-leisure (F1,154=5,299; p=0.023). The PAL-total changed in -16.7%, PAL-domestic in -7.6%, PAL-leisure in -48.6% (all p<0.05); and the PAL-sportive declined in 12.0% (F1,154=0.892; p=0.346). Concurrently with aging, there is a declined on PAL domains that could be related to domestic, exercise, or recreational activities. These results demonstrated the need to maximize public health policies with the purpose to improve the health status of older adults by increasing the PAL on different domains, and also to motivate older adults to maintain an active and independent lifestyle, mainly enrolling in exercise program, leading to positive effects on quality of life, and on the additional years of life of this population.

Ejercicio físico e inmunidad en el anciano / Physical exercises and immunology in elderly

Se realiza una revisión bibliográfica acerca de la temática del envejecimiento del sistema inmunológico (inmunosenescencia) habitual en los ancianos, y la práctica regular de ejercicios físicos, para conocer la actualidad del tema, debido al envejecimiento progresivo de la población mundial. La inmunosenescencia se caracteriza por una serie de cambios inmunes, enfermedades crónicas, incremento de la susceptibilidad para la infección, enfermedades tumorales y de las enfermedades autoinmunes, lo que representa peligro para estos individuos, aunque se han identificado estrategias terapéuticas importantes para el tratamiento en estas edades, como es la práctica regular de ejercicio físico moderado. Desde el punto de vista inmunológico, el anciano que no realiza ningún tipo de ejercicio físico, tiene disminuidos la mayor parte de sus biomarcadores de función celular y humoral, con reducción de la calidad y cantidad linfocitaria, de la supervivencia de los linfocitos T y B, además tiene baja autoestima y en ocasiones, desnutrición y enfermedades crónicas con deformidades estructurales. Sin embargo, la aplicación de estilos de vida saludables, como la práctica regular de ejercicios físicos, puede atenuar las consecuencias de este proceso y constituir una alternativa terapéutica en muchos casos

We review literature on the topic of aging immune system (immunosenescence) common in the elderly and regular physical exercise, to know today's issue, due to the progressive aging of world population. Immunosenescence is characterized by a number of immune changes, chronic diseases, increased susceptibility to infections, tumor diseases and autoimmune diseases, which pose a threat to these individuals, although important therapeutic strategies for treatments have been identified in these ages, such as the regular practice of moderate physical exercise. From the immunological point of view, the elder subjects who do not physical exercise, have reduced most of their biomarkers of cellular and humoral functions with reduced lymphocyte quantity and quality of survival of T and B cells; also these subjects have low self-esteem at times, malnutrition and chronic diseases with structural deformities. However, we conclude that the implementation of healthy lifestyles, and the regular practice of physical exercise may attenuate the consequences of this process, and provide a therapeutic alternative in many cases

A Imunologia da infecção pelo HIV em pacientes com idade avançada: caracterização fenotípica e funcional da resposta imune mediada pela célula T CD4+ / Immunology of HIV infection in patients with advanced age: phenotypic and functional immune response mediated by CD4+ cell

A proporção de idosos portadores da síndrome da imunodeficiência adquirida (aids) tem aumentado de maneira importante nos últimos anos e, até a presente data, existem poucos estudos que abordam a infecção nessa população especial. As particularidades imunológicas decorrentes do fenômeno da imunossenescência podem acarretar mudanças significativas na evolução da infecção pelo HIV, bem como na resposta ao tratamento. O objetivo maior desta Tese foi avaliar o impacto da idade na recuperação funcional do sistema imune de pacientes com aids acima de 55 anos, quando tratados adequadamente com terapia anti-retroviral, caracterizando a resultante imunológica da idade avançada e da infecção pelo HIV. Para tanto, foram estudados quatro grupos experimentais: indivíduos jovens saudáveis ou com aids, e indivíduos acima de 55 anos saudáveis ou com aids. Todos os pacientes com aids estavam recebendo terapia anti-retroviral, em sucesso terapêutico. No primeiro artigo apresentado, avaliamos resposta linfoproliferativa e produção de citocinas in vitro e resposta humoral in vivo mediante desafio antigênico com toxóide tetânico (TT) em indivíduos previamente vacinados contra o tétano. Os resultados mostraram deficiências imunológicas significativas relacionadas à idade avançada no que diz respeito a produção de IgG anti-TT, resposta linfoproliferativa e produção de IFN-y. Em contrapartida, a produção de IL-10 foi significativamente maior nos indivíduos acima de 55 anos, infectados ou não pelo HIV. No segundo artigo, foram caracterizadas as subpopulações de células T mediante estímulo policlonal ou específico com antígenos do envelope do HIV (Env). Em culturas não-estimuladas de PBMC do grupo com aids e idade avançada, observamos frequência reduzida de células T naive e de memória central, associada a aumento de células T efetoras. Quando estimuladas policlonalmente, essas culturas apresentaram deficiência na produção de IFN-y e hiperprodução de IL-10, como na resposta ao TT...

The proportion of aged persons living with the acquired immunodeficiency syndrome (aids) has importantly increased in recent years and, up to the present moment, there are few studies that address the infection in this particular population. The immunological nuances resulting from the immunosenescence phenomenon may promote significant alterations in the clinical course of HIV infection, as well as in treatment response. The major purpose of this Thesis was to evaluate the impact of age on the functional immune recovery in aids patients aged more than 55 years, when adequately treated with anti-retroviral therapy, characterizing the immunological result of advanced age and HIV infection. Thus, four experimental groups were enrolled: healthy or HIV-infected young adults, and healthy or HIV-infected adults over 55 years old. All the HIV-infected patients had diagnosis of aids and were under anti-retroviral treatment with therapeutic success. In the first presented article, we evaluated the lymphoproliferative response and cytokine production in vitro and humoral response in vivo, after antigenic challenge with tetanus toxoid (TT) in previously immunized individuals against tetanus. The results revealed significant age-related immunological impairments concerning anti-TT IgG production, lymphoproliferative response and production of IFN-y. On the other hand, the production of IL-10 significantly higher in individuals aged more the 55 years, HIV-infected or not. In the second article, T cell subsets were characterized after polyclonal activation or specific stimulus with antigens derived from the HIV envelope (Env). In fresh unstimulated PBMC cultures obtained from the aged aids patients, there was a reduced frequency of naïve and central memory T cells, associated with increased frequency of effector T cells. When polyclonally stimulated, these cultures showed deficient production of IFN-y and hyperproduction of IL-10, like in response to TT...

Exercício físico como fator de prevenção aos processos inflamatórios decorrentes do envelhecimento / Physical exercise as a preventive procedures inflammation of aging

Ao longo do processo de envelhecimento observa-se complexa remodelagem do sistema imunitário. Estas alterações estão associadas ao desenvolvimento de patologias responsáveis por grande parte da mortalidade em população idosa. Recentemente, a prática regular de atividades físicas tem sido proposta como intervenção não-medicamentosa com amplos benefícios sobre a regulação de processos decorrentes da imunossenescênia. Neste sentido, o presente trabalho revisou e discutiu estudos que abordam a ação de mediadores pró-inflamatórios crônicos e possíveis ações do exercício físico como agente antiinflamatório. Baseado nos resultados de estudos na literatura sugere-se que, em conjunto, a interleucina-6 (IL-6) e o fator de necrose tumoral-α (TNF- α) são as principais citocinas associadas à aterosclerose, sarcopenia e déficits cognitivos. Embora os mecanismos não sejam totalmente elucidados, o exercício reduz a atividade de citocinas pró-inflamatórias e aumenta a liberação de substancias anti-inflamatórias.

During the aging is observed complex remodeling of immune system. These changes are associated with the development of diseases responsible for much of the mortality in the elderly. Recently, the regular practice of exercise has been proposed as an intervention non-medication with broad benefits on regulation processes arising from Immunosenescence. In sense, this paper reviewed and discussed studies addressing the action of pro-inflammatory mediator’s chronic and possible actions of physical exercise as anti-inflammatory agent. Based on the results of studies in the literature suggest that, together, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are the main cytokines associated with atherosclerosis, sarcopenia and cognitive deficits. Though mechanisms are not fully elucidated, the Exercise reduces the activity of pro-inflammatory and increases the release of anti-inflammatory substances.

Effect of aging and oral tolerance on dendritic cell function

Oral tolerance can be induced in some mouse strains by gavage or spontaneous ingestion of dietary antigens. In the present study, we determined the influence of aging and oral tolerance on the secretion of co-stimulatory molecules by dendritic cells (DC), and on the ability of DC to induce proliferation and cytokine secretion by naive T cells from BALB/c and OVA transgenic (DO11.10) mice. We observed that oral tolerance could be induced in BALB/c mice (N = 5 in each group) of all ages (8, 20, 40, 60, and 80 weeks old), although a decline in specific antibody levels was observed in the sera of both tolerized and immunized mice with advancing age (40 to 80 weeks old). DC obtained from young, adult and middle-aged (8, 20, and 40 weeks old) tolerized mice were less efficient (65, 17 and 20 percent, respectively) than DC from immunized mice (P < 0.05) in inducing antigen-specific proliferation of naive T cells from both BALB/c and DO11.10 young mice, or in stimulating IFN-g, IL-4 and IL-10 production. However, TGF-â levels were significantly elevated in co-cultures carried out with DC from tolerant mice (P < 0.05). DC from both immunized and tolerized old and very old (60 and 80 weeks old) mice were equally ineffective in inducing T cell proliferation and cytokine production (P < 0.05). A marked reduction in CD86+ marker expression was observed in DC isolated from both old and tolerized mice (75 and 50 percent, respectively). The results indicate that the aging process does not interfere with the establishment of oral tolerance in BALB/c mice, but reduces DC functions, probably due to the decline of the expression of the CD86 surface marker.

Klotho: un nuevo eslabón en la fisiopatología de la insuficiencia renal crónica / Klotho: a new link in the pathophysiology of chronic kidney disease insufficiency

Klotho, a recently described gene, is mainly expressed in the kidney, and encodes a protein necessary for the activity of fibroblast growth factor receptors (FGFR), especially FGFR1. The Klotho protein has two variants, a transmembrane and a secreted form, and the latter may represent a new hormone synthesized by the kidney. Recent studies have shown that chronic kidney disease (CDK) is associated with significant alterations in the expression of klotho, and this alteration seems to be responsible for many of the phenotypic characteristics that accompany the uremic syndrome. CKD is associated with marked lymphocyte dysfunction, a clinically relevant problem, but the pathophysiological mechanisms behind this dysfunction are mostly unknown. Our research group has recently demonstrated the expression of klotho andFGFR1 in human lymphocytes and is currently implementing a series of experiments designed to determine the role of this pathway in the pathogenesis of lymphocyte dysfunction associated with uremia.

As conseqüências das deficiências nutricionais, associadas à imunossenescência, na saúde do idoso: [revisão] / The consequences of nutritional deficits associated to immunosenescence in the health of elderly: [review]

Atualmente tem-se registrado um aumento médio da expectativa de vida em diversos países, fazendo com que a prevalência de indivíduos idosos em relação aos indivíduos jovens, torne-se um quadro comum na população mundial. Entretanto, a longevidade está longe de significar um envelhecimento saudável. Das diversas funções do organismo afetadas pelo complexo processo do envelhecimento, o sistema imune em particular, sofre várias mudanças coletivamente chamadas de imunossenescência. Já as outras alterações observadas no idoso, em parte são condicionadas pelos processos inerentes ao envelhecimento, e outras influenciadas por fatores socioeconômicos, que levam a inúmeros distúrbios nutricionais. Desta forma, o presente trabalho, teve como objetivo apresentar as principais causas da má nutrição nos idosos, sintetizar os principais efeitos da idade na imunidade e, sobretudo, chamar a atenção para o fato de que a associação entre imunossenescência e as carências nutricionais, agrava ainda mais a saúde do idoso, tornando-o mais susceptível a doenças infecciosas. Para isso foram identificados e analisados 78 trabalhos publicados sobre o assunto entre os anos de 1969 e 2008, tendo como fontes principais para a pesquisa os bancos de dados LILACS -BIREME, MEDLINE - Index Medicus, SciELO e PubMed. Diversos estudos têm demonstrado que na medida em que intervenções nutricionais específicas são introduzidas na população de idosos, os efeitos deletérios da imunossenescência podem ser minimizados.

Nowadays, several countries have registered an increase in the life span of the population. It means that the prevalence of elderly is higher than young people around the world. However, the longevity is not so far linked to a healthy aging process. Amongst physiological systems that are changed by aging, immune system is particularly affected by a process called immunosenescence. Other alterations that are observed in elderly belong to normal process of aging. On the other hand, socioeconomics factors can lead to several nutritional disturbs. Thus, the present study shows the main causes of malnutrition in elderly, the effects of age on immunity, and the relationship between immunosenescence and nutritional deficits. It was identified and analyzed 78 studies published between 1969 and 2008 in the data basis LILACS -BIREME, MEDLINE - Index Medicus, SciELO e PubMed. Many studies have demonstrated that specific nutritional interventions can minimize the deleterious effects of immunosenescence.

Aging reduces the primary humoral response and the in vitro cytokine production in mice

Aging is accompanied by a decrease in several physiological functions that make older individuals less responsive to environmental challenges. In the present study, we analyzed the immune response of female BALB/c mice (N = 6) of different ages (from 2 to 96 weeks) and identified significant age-related alterations. Immunization with hapten-protein (trinitrophenyl-bovine serum albumin) conjugates resulted in lower antibody levels in the primary and secondary responses of old mice (72 weeks old). Moreover, young mice (2, 16, and 32 weeks old) maintained specific antibodies in their sera for longer periods after primary immunization than did old mice. However, a secondary challenge efficiently induced memory in old mice, as shown by the increased antibody levels in their sera. The number of CD4+ and CD8+ T cells in the spleen increased until 8 weeks of age but there was no change in the CD4+/CD8+ ratio with aging. Splenic T cells from old mice that had or had not been immunized were less responsive to concanavalin-A and showed reduced cytokine production compared to young mice (IL-2: 57-127 vs 367-1104 pg/mL, IFN-g: 2344-12,836 vs 752-23,106 pg/mL and IL-10: 393-2172 vs 105-2869 pg/mL in old and young mice, respectively). These data suggest that there are significant changes in the organization of the immune system throughout life. However, the relevance of these alterations for the functioning of the immune system is unknown.

Age related changes in Fas (CD95) and Fas ligand gene expression and cytokine profiles in healthy Indians.

Ageing in human and animal models show changes in many aspects of protective immunity, particularly lymphopoenia and progressive decline in immune functions leading to increased frequency of infection and neoplasia. However, the exact mechanism of these defects is still unclear. In this study, elderly subjects showed a decline in CD3+ and CD4+ T-cell subsets as well as serum IL-2 levels. Serum IL-6 was significantly raised while expression of its signaling receptor gp130 was significantly impaired in elderly as compared to the younger ones. Additionally, all the elderly individuals showed constitutive expression of Fas and FasL mRNA; however, none of the younger individuals expressed mRNA transcripts constitutively although induced expression was seen in both the groups. Similarly, frequency of Fas and FasL expressing CD4+ and CD8+ T-cell subsets were significantly (p < 0.001) higher in elderly subjects as compared to the younger ones. Elderly individuals also showed a significantly (p < 0.001) higher frequency of activation induced cell death (AICD). Since interaction of Fas with its cognate ligand (FasL) activates death inducing caspases leading to apoptosis, and gp130 induces anti-apoptotic signal through STAT-3 pathway, these results suggest that the decline in protective immune functions in aged individuals may be related to Fas and FasL mediated apoptosis of peripheral T-cell subsets.

Papel da atividade física regular realizada durante vários anos na função imune do idoso / Role of regular practice of physical activity over several plus om immune function in the elderly

Para avaliar o efeito da atividade física regular na imunosenescência, comparou-se parâmetros imunológicos de 20 idosos corredores aos de 20 idosos sedentários e 10 jovens sedentários. Os idosos corredores apresentaram resposta proliferativa de linfócitos T a OKT-3 e produção de interleucina-2 maiores do que os idosos sedentários, porém similares aos jovens. Eles apresentaram produção de interleucina-3 menor, mas também semelhante aos jovens. A interleucina-6 sérica deles foi menor do que a dos idosos sedentários. Conclui-se que a prática regular de atividade física por longos anos tem o potencial de desacelerar a imunosenescência / To access the effect of regular physical activity on immunosenescence, the immunological parameters of 20 elderly runners were compared to those of 20 elderly sedentary persons and 10 sedentary young persons. The running elderly subjects presented a higher T lymphocyte proliferative response to OKT-3 and a higher interleukin-2 production than elderly sedentary subjects, but similar to that of young subjects, plus a lower production of interleukin-3, but also similar to that of young subjects. Their serum interleukin-6 was lower than that of sedentary elderly subjects. We conclude that practicing regular physical activity for many years has the potential to decelerate immunosenescence...