O efeito do tratamento com rapamicina em órgãos linfoides de camundongos propensos à senescência acelerada / The effect of rapamycin treatment on lymphoid organs of senescence accelerated mice prone

Envelhecer compreende um fenômeno complexo, natural e irreversível, que submete o organismo a inúmeras alterações nos processos biológicos, fisiológicos, ambientais, psicológicos, comportamentais e sociais. Esse processo é caracterizado por um declínio gradual dos mecanismos homeostáticos do organismo, intimamente relacionados com o estado senescente. A senescência, quando diz respeito ao sistema imunológico, é denominada de imunossenescência, que pode ser definida como uma parada estável do ciclo celular associada a mudanças, com uma resposta que limita a proliferação de células envelhecidas ou danificadas. A autofagia está diretamente relacionada com a manutenção do fenótipo senescente, em que a atividade autofágica exerce um papel essencial e ativo na influência da biossíntese de proteínas e organelas. Essa via é regulada naturalmente pela proteína mTOR e quimicamente pelo fármaco rapamicina. Assim, pretendemos investigar: (1) as alterações no perfil corporal e hematimêtrico dos animais ao longo do tratamento com rapamicina; (2) avaliar o perfil de citocinas; (3) observar as modificações histológicas em órgãos linfoides primários e secundário; (4) analisar as populações de células linfoides e mieloides; e (5) avaliar a capacidade proliferativa de linfócitos in vitro. Camundongos SAMP-8 e SAMR-1 foram tratados com rapamicina durante dois meses. A mensuração da massa corporal e análises hematológicas foram realizadas antes e durante o tratamento. Amostras de soro, medula óssea, timo e baço foram analisados em ensaios de ELISA, histologia, população e subpopulações de células. Alterações na massa corporal, parâmetros hematológicos e celularidade de células foram nítidas entre os dois modelos utilizados. Diferenças também foram percebidas na detecção de citocinas IL-1ß. IL-6 e TNF-α, com resultados significantes nas amostras de baço, timo e medula óssea. As citocinas IL-7 e IL-15 apresentaram diferenças de secreção entre os grupos, sendo a primeira maior detectada em camundongos com senescência acelerada tratados com rapamicina. Em nossa análise histológica observamos que os camundongos SAM-P8 apresentaram involução tímica. E nas subpopulações de linfócitos T do baço, células TCD4+ e TCD8+ estavam, respectivamente, em maior e menor quantidade nos camundongos SAM-P8 tratados com rapamicina. Dessa forma, o camundongo da linhagem SAM-P8 é um excelente modelo para se estudar as alterações da senescência, em que o mesmo apresenta características fisiológicas distintas dos camundongos utilizados como controle (SAM-R1). Além disso, verificamos que a dose de rapamicina empregada não desencadeou alterações que pudessem comprometer a resposta imunológica desses camundongos, bem como na possibilidade de atuar na resposta contra os efeitos complexos do envelhecimento

Aging comprises a complex, natural, and irreversible phenomenon, which subjects the organism to countless alterations in biological, physiological, environmental, psychological, behavioral, and social processes. This process is characterized by a gradual decline in the organism's homeostatic mechanisms, closely related to senescence effects. Senescence, when it concerns the immune system, is called immunosenescence, which can be defined as a stable cell cycle arrest associated with changes and is a response that limits the proliferation of aged or damaged cells. Autophagy is a genetically regulated, conserved cellular process and a metabolic pathway essential for maintaining cellular homeostasis, which plays a constitutive and active role in controlling the biosynthesis of proteins and organelles. This pathway is regulated naturally by mTOR or chemically by the drug rapamycin, having a direct relationship with cellular homeostasis and maintenance of the senescent phenotype. Thus, we intend to investigate: (1) the changes in the body and hematimetic profile of the animals throughout the rapamycin treatment; (2) evaluate the cytokine profile; (3) observe histological changes in primary and secondary lymphoid organs; (4) analyze lymphoid and myeloid cell populations; and (5) evaluate the proliferative capacity of lymphocytes in vitro. SAMP-8 and SAMR-1 mice were treated with rapamycin for two months. Body mass measurement and hematological analyses were performed before and during treatment. Serum, bone marrow, thymus and spleen samples were analyzed in ELISA assays, histology, cell population and subpopulations. Changes in body mass, hematological parameters, and cellularity were clear between the two models used. Differences were also noticed in the detection of cytokines IL-1ß. IL-6 and TNF-α, with significant results in the spleen, thymus and bone marrow samples. The cytokines IL-7 and IL-15 showed differences in secretion between groups, the former being higher detected in mice with accelerated senescence treated with rapamycin. In our histological analysis we observed that SAM-P8 mice showed thymic involution. And in the spleen T-lymphocyte subpopulations, TCD4+ and TCD8+ cells were, respectively, in higher and lower quantities in SAM-P8 mice treated with rapamycin. Thus, the SAM-P8 mouse is an excellent model to study the changes of senescence, since it presents physiological characteristics different from the control mice (SAM-R1). Furthermore, we verified that the dose of rapamycin used did not trigger changes that could compromise the immune response of these mice, as well as the possibility of acting in the modulatory response against the complex effects of aging

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.

Respuesta inmune y alergia a vacunas / Immune response and allergies to vaccines

Las vacunas son altamente efectivas en prevenir enfermedades infecciosas a través del desarrollo en el individuo de una respuesta inmune protectora, sin desarrollar la enfermedad. Los distintos tipos de vacunas producen diferentes tipos de respuestas inmunes y variadas estrategias se han desarrollado para mejorar esta respuesta. El sistema inmune sufre cambios con la edad y esta inmunosenecencia altera la capacidad de responder frente a ellas. Por otro lado, si bien el sistema inmune puede reconocer elementos presentes en las vacunas y montar respuestas de hipersensibilidad ante ellos, las alergias a las vacunas son raras, teniendo que distinguirlas adecuadamente de otro tipo de reacciones. En caso que un paciente presente una reacción compatible con alergia, es importante conocer todos los componentes de la vacuna para realizar un estudio adecuado.

Vaccines are highly effective in preventing infectious diseases through the development in the individual a protective immune response, without developing the disease. Different types of vaccines produce different types of immune responses, and varied strategies have been developed to improve this response. The immune system undergoes changes with age, and this inmunosenescence alters the ability to respond to them. On the other hand, although the immune system can recognize elements present in vaccines and establish hypersensitivity responses to them, vaccine allergies are rare, having to properly distinguish them from other types of reactions. In the event that a patient has an allergy-compatible reaction, it is important to know all the components of the vaccine to conduct a proper study.

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.

COPD as a Disease of Immunosenescence

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.

Aging and the Immune System: the Impact of Immunosenescence on Viral Infection, Immunity and Vaccine Immunogenicity

Immunosenescence is characterized by a progressive deterioration of the immune system associated with aging. Multiple components of both innate and adaptive immune systems experience aging-related changes, such as alterations in the number of circulating monocytic and dendritic cells, reduced phagocytic activities of neutrophils, limited diversity in B/T cell repertoire, T cell exhaustion or inflation, and chronic production of inflammatory cytokines known as inflammaging. The elderly are less likely to benefit from vaccinations as preventative measures against infectious diseases due to the inability of the immune system to mount a successful defense. Therefore, aging is thought to decrease the efficacy and effectiveness of vaccines, suggesting aging-associated decline in the immunogenicity induced by vaccination. In this review, we discuss aging-associated changes in the innate and adaptive immunity and the impact of immunosenescence on viral infection and immunity. We further explore recent advances in strategies to enhance the immunogenicity of vaccines in the elderly. Better understanding of the molecular mechanisms underlying immunosenescence-related immune dysfunction will provide a crucial insight into the development of effective elderly-targeted vaccines and immunotherapies.

Effects of natural aging and gender on pro-inflammatory markers

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.

The role of senescence of bone marrow cells in acute kidney injury

BACKGROUND: The prevalence of acute kidney injury (AKI) in elderly patients has grown considerably. Age-associated changes in the immune system can be one of the critical factors determining AKI outcomes. This study aimed to investigate the role of senescence of bone marrow (BM)-derived cells in the development of AKI, focusing on the immune response. METHODS: Female 7-week-old C57BL/6 mice were irradiated and treated with BM cells from either 48-week-old or 8-week-old male mice. Ischemia-reperfusion injury (IRI) was induced, and their functional deterioration, histological tubular damage, and inflammatory responses were compared. For the in-vitro study, lipopolysaccharide (LPS)-stimulated cytokine production by BM cells from old and young mice were examined. RESULTS: At 24 hours after IRI, there was no significant difference in the number of circulating immune cells between the mice transplanted with old or young BM cells. However, the mice with old BM cells showed less functional deterioration and histological tubular injury than those with young BM cells. Moreover, macrophage infiltration and renal cytokine interleukin (IL)-12 levels were lower in the mice with old BM cells at 24 hours post-IRI. Consistently, the in vitro study showed that LPS-induced production of cytokines interferon-γ, monocyte chemoattractant protein-1, and IL-10 was attenuated in cultured old BM cells, suggesting that age-related functional changes in these cells may lead to reduced inflammation in IRI. CONCLUSION: Immunosenescence could affect the susceptibility and response to renal IRI. Further studies specifically addressing age-related alterations can help in the development of treatment strategies for elderly patients with AKI.

Manipulación de la inmunosenescencia / Immunosenescence manipulation

En la actualidad existe un aumento del envejecimiento poblacional en Cuba y a nivel mundial, consecuencia del éxito de las políticas de salud pública y del desarrollo socioeconómico. Con el incremento progresivo de la edad se evidencian cambios en el sistema inmunológico que contribuyen a una susceptibilidad incrementada a las enfermedades infecciosas, condiciones patológicas relacionadas con la inflamación, enfermedades autoinmunes, el cáncer y se manifiesta una respuesta reducida ante la vacunación. La manipulación de la inmunosenescencia a través de diferentes terapéuticas se espera que contribuya al rejuvenecimiento del sistema inmune y por consiguiente a la restauración de la inmunidad en individuos inmunocomprometidos, al control del cáncer y al incremento de la eficacia de la vacunación en ancianos(AU)

There is an increase of population aging in Cuba and globally, as a result of the success of public health policies and socio-economic development. With the progressive increase in age, there are changes in the immune system that contribute to an increased susceptibility to infectious diseases, pathological conditions related to inflammation, autoimmune diseases, cancer and a reduced response to vaccination. The manipulation of immunosenescence through different therapies has been studied. It is expected to possibly contribute to the 'rejuvenation' of the immune system and consequently, to the restoration of immunity in immunocompromised individuals, the improvement of the effectiveness of vaccination in the elderly and the control of cancer(AU)

Association between inflammatory mediators, grip strength and mobility in community-dwelling elderly / Associação entre mediadores inflamatórios, força de preensão manual e mobilidade em idosos da comunidade / Asociación entre mediadores inflamatorios, fuerza de la empuñadura y la movilidad en ancianos de la comunidad

Abstract Introduction: Aging is associated with loss of muscle mass, immunosenescence and increased production of inflammatory mediators, high levels being predictors of a decline in functional capacity in the elderly. Objective: To assess the association between inflammatory mediators, interleukin 6 (IL-6) and C-reactive protein (CRP) and functional capacity in the elderly. Methods: Cross-sectional study with 308 community-dwelling elderly. The study was approved by the Research Ethics Committee, under protocol number 067/2010. Grip strength (GS) was measured using a JAMAR® dynamometer and functional capacity by the Timed Up and Go (TUG) test. Blood tests were performed and serum levels of C-reactive protein and interleukin 6 assessed. Spearman's coefficient was applied to analyze the correlation between variables and the Mann-Whitney for intergroup comparison. Significance was set at 0.05. Results: There was no significant correlation between GS, the TUG and inflammatory mediators (CRP and IL-6). However, by adjusting for variables such as age, sex and muscle mass, a significant and inverse correlation (p = 0.023) was observed between GS and CPR. Conclusion: Elderly subjects with low C-reactive protein levels performed better in the grip strength test. It is important to investigate the adverse effects on functional capacity that can be influenced by inflammatory cytokines in the elderly during aging.

Resumo Introdução: O envelhecimento está relacionado a perda de massa muscular, imunossenescência e o aumento da produção de mediadores inflamatórios, cujos níveis elevados são preditores do declínio da capacidade funcional na população idosa. Objetivo: Avaliar a associação entre mediadores inflamatórios, interleucina-6 (IL-6) e proteína C-reativa (PCR) e capacidade funcional no idoso. Métodos: Estudo transversal com 308 idosos da comunidade. O estudo foi aprovado pelo Comitê de Ética e Pesquisa, 067/2010. A força de preensão manual (FPM) foi avaliada através do dinamômetro de JAMAR® e a capacidade funcional pelo teste Timed Up and Go. Foi realizado um exame de sangue e analisados os níveis séricos de proteína C-reativa e interleucina-6. Utilizou-se o coeficiente de Spearman para verificar a correlação entre as variáveis e o teste de Mann-Whitney para comparação entre os grupos. O nível de significância utilizado foi de 0,05. Resultados: Não houve correlação significativa entre a FPM e o Timed Up and Go e os mediadores inflamatórios (PCR e IL-6). Porém, ao controlar as variáveis como idade, gênero e índice de massa muscular encontrou-se uma associação significativa e inversa (p = 0,023) entre a FPM e os níveis de PCR. Conclusão: Idosos com baixos índices de proteína C-reativa apresentaram melhor desempenho no teste de força muscular manual. É destacável a importância da investigação dos desfechos adversos que podem ser influenciados pela citocinas inflamatórias na capacidade funcional dos idosos durante o envelhecimento.

Resumen Introducción: El envejecimiento se relaciona con una pérdida de masa muscular, inmunosenescencia, tanto el aumento de la producción de mediadores inflamatorios, cuyos niveles elevados son predictores de disminución de la capacidad funcional en la población de edad avanzada. Objetivo: Investigar la asociación entre mediadores inflamatorios, interleucina-6 (IL-6) y proteína C reactiva (CRP) y capacidad funcional en los ancianos. Métodos: Estudio transversal con 308 ancianos de la comunidad. El estudio fue aprobado por el Comité de Ética e Investigación, 067/2010. La fuerza de la empuñadura (GS) se evaluó utilizando el dinamómetro JAMAR® y la capacidad funcional mediante la prueba Timed Up and Go. Se realizó un análisis de sangre y se analizaron los niveles séricos de proteína C reactiva e interleucina-6. El coeficiente de Spearman se utilizó para verificar la correlación entre las variables y la prueba de Mann-Whitney para la comparación entre los grupos. El nivel de significancia fue 0,05. Resultados: No hubo correlación significativa entre GS y Timed Up and Go y mediadores inflamatorios (CRP e IL-6). Sin embargo, cuando se controlaron variables como la edad, el sexo y el índice de masa muscular, hubo una asociación significativa (p = 0,023) entre los niveles de GS y CRP, es decir, los individuos que obtuvieron buenos resultados en el GS obtuvieron niveles más bajos de PCR circulante. Conclusión: Los pacientes ancianos con bajos niveles de proteína C reactiva, presentaron mejor desempeño en la prueba de fuerza muscular manual. Es importante investigar los efectos adversos que pueden estar influenciados por las citosinas inflamatorias sobre la capacidad funcional de los ancianos durante el envejecimiento.

Zona en milieu hospitalier à Cotonou de 2005 à 2014: aspects épidemiologiques et cliniques

L'objectif de cette étude était de documenter les aspects épidémiologiques et cliniques du zona en milieu hospitalier à Cotonou. Matériel et méthodes : L'étude était rétrospective et descriptive sur 10 ans et a concerné tous les nouveaux patients reçus en consultation dans le service de Dermatologie du Centre National Hospitalier et Universitaire de Cotonou (CNHU-C), chez qui le diagnostic clinique de zona a été retenu. Résultats : Sur les 10787 nouveaux patients reçus durant la période, 70 présentaient un zona correspondant à une prévalence de 0,6%. Le sex-ratio H/F était de 1,1. La moyenne d'âge était de 42,3 ans avec des extrêmes de 1 an et 73 ans. La tranche d'âge la plus touchée était celle des patients de 50-60 ans. L'infection à VIH était associée au zona dans 46,9% des cas. Les formes érythémato-vésiculeuses à disposition unilatérale étaient prédominantes (79%). Les formes nécrotiques (10%) et nécrotico-hémorragiques (4%) étaient l'apanage des patients infectés par le VIH. Conclusion : Le zona était une dermatose rare dans le service de dermatologie du CNHU- C. L'immunodéficience par le VIH et l'immunosénescence étaient les principaux facteurs de co-morbidité

Immune System Dysfunction in the Elderly

ABSTRACT Human aging is characterized by both physical and physiological frailty that profoundly affects the immune system. In this context aging is associated with declines in adaptive and innate immunity established as immunosenescence. Immunosenescence is a new concept that reflects the age-associated restructuring changes of innate and adaptive immune functions. Thus elderly individuals usually present chronic low-level inflammation, higher infection rates and chronic diseases. A study of alterations in the immune system during aging could provide a potentially useful biomarker for the evaluation of immune senescence treatment. The immune system is the result of the interplay between innate and adaptive immunity, yet the impact of aging on this function is unclear. In this article the function of the immune system during aging is explored.

Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) cohort: study protocol and results of the first 3 years of enrollment / 한국역학회지

Although the etiologies of cardiovascular disease (CVD) are widely understood, the goal of finding a globally effective solution for preventing CVD is unrealistic. Therefore, we aimed to conduct a community-based prospective study on the prevention and management of CVD in Korean adults. This study was designed to recruit 8,000 healthy adults over the course of 5 years. The baseline assessment includes a wide range of established CVD risk factors, including demographic characteristics, medical history, health behaviors, psychological conditions, body size and composition, blood pressure, the augmentation index, carotid ultrasonography, an electrocardiogram, and biochemical indicators, as well as some novel factors, such as social network characteristics, exposure to environmental pollutants, inflammatory markers, hemostatic markers, and immunosenescence markers. Annual telephone interviews and follow-up health examinations at 5-year intervals after the baseline assessment are planned to collect information on changes in health status and its determinants. Additionally, indirect follow-up using secondary data sources will be conducted to obtain information on health services utilization and death. So far, more than 6,000 adults have been enrolled during the first three and a half years, and almost all participants have been tracked by annual telephone follow-up surveys. The data have been uploaded to iCReaT, the clinical research information management system of the Korea National Institute of Health.

Cardiovascular and Metabolic Diseases Etiology Research Center (CMERC) cohort: study protocol and results of the first 3 years of enrollment / 한국역학회지

Although the etiologies of cardiovascular disease (CVD) are widely understood, the goal of finding a globally effective solution for preventing CVD is unrealistic. Therefore, we aimed to conduct a community-based prospective study on the prevention and management of CVD in Korean adults. This study was designed to recruit 8,000 healthy adults over the course of 5 years. The baseline assessment includes a wide range of established CVD risk factors, including demographic characteristics, medical history, health behaviors, psychological conditions, body size and composition, blood pressure, the augmentation index, carotid ultrasonography, an electrocardiogram, and biochemical indicators, as well as some novel factors, such as social network characteristics, exposure to environmental pollutants, inflammatory markers, hemostatic markers, and immunosenescence markers. Annual telephone interviews and follow-up health examinations at 5-year intervals after the baseline assessment are planned to collect information on changes in health status and its determinants. Additionally, indirect follow-up using secondary data sources will be conducted to obtain information on health services utilization and death. So far, more than 6,000 adults have been enrolled during the first three and a half years, and almost all participants have been tracked by annual telephone follow-up surveys. The data have been uploaded to iCReaT, the clinical research information management system of the Korea National Institute of Health.

ASMA EN ADULTOS MAYORES / Asthma in older adults

El asma se ha considerado a menudo como una enfermedad cuyo inicio se produce en la infancia. Sin embargo, recientes estudios poblacionales han informado que el inicio del asma es común en las personas mayores. La carga sanitaria, personal y económica del asma puede ser más significativa en los ancianos que en sus homólogos más jóvenes, particularmente en lo que se refiere a la mortalidad, la hospitalización, los costos médicos o la calidad de vida relacionada con la salud. El asma en el Adulto Mayor (AAM) sigue siendo subdiagnosticada y subtratada. El objetivo principal de esta Revisión es identificar las necesidades no satisfechas en los campos de investigación y práctica para AAM, así como encontrar nuevas direcciones de investigación, proponer nuevas estrategias terapéuticas y mejorar los resultados para el creciente número de personas mayores con asma. El desafío de hoy es fomentar la investigación en AAM, utilizando el conocimiento existente para mejorar el diagnóstico, y los diagnósticos deferenciales, así como educar al paciente, desarrollar un enfoque terapéutico seguro y eficaz, controlar la enfermedad y, finalmente, proporcionar una mejor calidad de vida(AU)

Asthma has often been considered as a childhood disease. However, recent population studies reported that asthma is common in the elderly The burden of asthma may be more significant in the elderly than in their younger counterparts, particularly with regard to mortality, hospitalization, medical costs or health-related quality of life.Asthma in the Elderly (AIE) is still under-diagnosed and under-treated. The primary aim of this review is to identify unmet needs in the fields of research and practice for AIE. This will enable us to find new research directions, propose new therapeutic strategies, and ultimately improve outcomes for elderly people with asthma. The challenge today is to encourage new research in AIE, but to already use existing knowledge we have to make the diagnosis of AIE, educate the patient, develop a therapeutic approach to control the disease, and ultimately provide a better quality of life to our elderly patients(AU)