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Aging, Nutritional Status, and Infection in the Developing World
Abstract
The fast rate of increase in the number of older people in less-developed countries threatens to further strain the limited health resources of these countries. However, very little is known about their health status and the risk factors that contribute to it. In this article, we review the burden of infectious diseases in elderly people in less-developed countries, discuss the contribution of nutrition and immune response to morbidity and mortality, identify gaps in current knowledge, and suggest strategies to address this fast-growing public health problem.
... For many, the prospect of a longer life may seem more like a punishment than a prize." A primordial objective is not only to increase lifespan but to achieve successful ageing, which is defined as minimizing the time between the onset of illness and death 3 . ...
... It has been established that that T cell decline is the main cause of immune senescence 3,19 . There is reduced number of naïve T cells, and an expansion of memory T cells 11 . ...
... There are several comprehensive reviews of micronutrient supplementation studies in the elderly 3,23 . Single nutrient supplementation studies have shown improvement in the immune response of the elderly. ...
... However, factors which may contribute to lowered immunogenicity of vaccines have not been well studied. Thus, although it is well established that zinc has an influence on multiple aspects of the immune system, including the normal development, differentiation, and function of cells belonging to both innate and acquired immunity (101,134,183), the mechanisms responsible for the positive effects of zinc treatment observed after vaccination as well as in diseases such as diarrhea, pneumonia and shigellosis have not been elucidated. Studies have also shown that zinc supplementation may increase the immunogenicity of Dukoral in older children in Bangladesh (4) as well as in Norwegian adults (77), and Bangladeshi infants showed a serotype specific increase in response to a pneumococcal conjugate vaccine when given zinc (107). ...
... This may suggest that T cells and B cells have different requirements for zinc for optimal function but need to be confirmed in a lager study. It has been speculated that supplementation with zinc during vaccination may hinder efficient vaccination responses in children who are zinc sufficient already before zinc supplementation (101,108) and suppressive effects on antitoxic antibody responses by zinc have been observed in studies in older children and adults (77,118). ...
Vibrio cholerae O1 and enterotoxigenic Escherichia coli (ETEC) together account for the majority of bacterial causes of acute dehydrating diarrhea in children in Bangladesh. Vaccines should be considered as an important public health tool for prevention of these diarrheal diseases. However, a limitation for the use of vaccines in developing countries is that the efficacy and immunogenicity of vaccines, especially oral enteric vaccines, are lower in these countries than in the industrialized world. The main objectives of the thesis were to study the safety and immunogenicity of oral cholera toxin B subunit (CTB) containing inactivated whole cell ETEC and cholera vaccines in young children in a developing country and to identify possible immune modulating factors, e.g. vaccine dose, different buffer formulations, effects of breast milk withholding and zinc supplementation. For determining optimal doses of the ETEC vaccine, we immunized 6 months to 12 year old children with full, half and quarter doses of the ETEC vaccine. Safety and immunogenicity of different vaccine doses were compared. All doses of the ETEC vaccine were found to be equally immunogenic in the older children. However, a quarter dose, although giving somewhat lower antibacterial responses than a full dose, was required for children 6-18 months to avoid reactogenicity. For determining the safety and immunogenicity of the cholera vaccine in young children and the effect of different interventions to try to enhance immune responses, children 6-18 months of age were given two doses of the vaccine according to the standard protocol or with different modifications. In addition to analyzing antibacterial and antitoxic B-cell responses, T-cell responses were determined using a new flowcytometric technique, FASCIA. The vaccine was found to be safe and to induce both antibody and Th1 type T-cell responses. Vibriocidal antibody responses were improved by temporarily withholding breast-feeding for three hours before immunization as well as by giving 20 mg of zinc from 3 weeks prior to and one week after the second dose of vaccine. Zinc supplementation also enhanced IFN- responses to CTB. Further objectives of this thesis were to analyze the immune responses to one of the most prevalent ETEC colonization factors (CFs), i.e. CS6, in patients infected with CS6-positive ETEC and to evaluate if there is an association between expression of certain Lewis blood group antigens of the host and infection by ETEC expressing different CFs. Natural infection with CS6 ETEC was found to induce robust systemic and mucosal immune responses in 70-90% of adults and children with diarrhea caused by CS6 positive ETEC strains, suggesting that CS6 could be an important immunogenic component of a new ETEC vaccine. We could also show that individuals with Le (a+b-) blood group had increased susceptibility to infection with ETEC expressing CFA/I group fimbriae. The results of these studies give important background information regarding the possibility of inducing effective immune responses to oral inactivated enteric vaccines in young children in developing countries.
... A long life of carrying heavy loads leads to low back pain causing severe functional disability [30]. In old age immunity is reduced increasing risk for infectious diseases [31]. Poor oral and dental health, poverty, a desire to give their food to their children or grandchildren, and lack of access to a variety of foods all adversely affect nutritional status [31,32] . ...
... In old age immunity is reduced increasing risk for infectious diseases [31]. Poor oral and dental health, poverty, a desire to give their food to their children or grandchildren, and lack of access to a variety of foods all adversely affect nutritional status [31,32] . Long exposure to indoor smoke and occupational hazards can result in chronic respiratory diseases. ...
ABSTRACT:
Low and middle income countries are ageing at a much faster rate than richer countries, especially in Asia. This is happening at a time of globalisation, migration, urbanisation, and smaller families. Older people make significant contributions to their families and communities, but this is often undermined by chronic disease and preventable disability. Social participation can help to protect against morbidity and mortality. We argue that social participation deserves much greater attention as a protective factor, and that older people can play a useful role in the prevention and management of chronic conditions. We present, as an example, a low-cost, sustainable strategy that has increased social participation among elders in Sri Lanka.
Current international policy initiatives to address the increasing prevalence of non-communicable chronic diseases are focused on cardiovascular disease, diabetes, respiratory disease and cancers, responsible for much premature mortality. Interventions to modify their shared risk factors of high salt and fat diets, inactivity, smoking and alcohol use are advocated. But older people also suffer chronic conditions that primarily affect quality of life, and have a wider range of risk factors. There is strong epidemiological and physiological evidence that social isolation, in particular, is as important a risk factor for chronic diseases as the 'lifestyle' risk factors, yet it is currently neglected. There are useful experiences of inexpensive and sustainable strategies to improve social participation among older people in low and lower middle income countries. Our experience with forming Elders' Clubs with retired tea estate workers in Sri Lanka suggests many benefits, including social support and participation, inter-generational contact, a collective voice, and facilitated access to health promotion activities, and to health care and social welfare services.
Policies to address the increase in chronic non-communicable diseases should include consideration of healthy ageing, conditions that affect quality of life, and strategies to increase social participation. There are useful examples showing that it is feasible to catalyse the formation of Elders' Clubs or older people's associations which become self-sustaining, promote social participation, and improve health and well-being of elders and their families.
... Although nutrition, immune function, and infection are clearly interrelated, it is no simple matter to quantify these relationships (70). Some agents used in intervention studies are listed in Table 2. Most of our current understanding relates to nutrient deficiency states and acute infections, and often investigations occur in hospitalized patient settings. ...
... In this context, available data 71 PHYSIOLOGY • Volume 23 • April 2008 • www.physiologyonline.org The different strategies to restore age-associated immune dysfunctions are shown (57,70,91,102). An increase or activation of the pathway/process is represented by + and a decrease/inhibition by -. ...
Accumulating data are documenting an inverse relationship between immune status, response to vaccination, health, and longevity, suggesting that the immune system becomes less effective with advancing age and that this is clinically relevant. The mechanisms and consequences of age-associated immune alterations, designated immunosenescence, are briefly reviewed here.
... In addition, poor nutrition has severe consequences for the immune response in the elderly and it becomes even more serious health the same when associated with typical immunosenescence frame. Thus, the vicious cycle between nutritional deficiencies and infections related to immunosenescence is a very vulnerable condition in the population above 60 years old (21). ...
... In addition, poor nutrition has severe consequences for the immune response in the elderly and it becomes even more serious health the same when associated with typical immunosenescence frame. Thus, the vicious cycle between nutritional deficiencies and infections related to immunosenescence is a very vulnerable condition in the population above 60 years old (21). ...
Introduction:
social or school factors influence the acquisition and selection of foods to be consumed.
Objective:
identifying the socioeconomic or school level that has the greatest weight in the acquisition of food in Mexican households.
Methods:
cross-sectional, retrospective and comparative study based on the database of the 2018 National Household Expenditure-Income Survey of Mexico. We worked with the national total of 73,274 Mexican households. The variables considered were: expenditure module of food and beverages, school grade of the head of the family and socioeconomic status to which the household belongs. For the statistical analysis, the following tests were used: linear regression analysis, as well as variance analysis, Snedecor's F test, post-hoc test and Schefé's confirmatory test.
Results:
socioeconomic status has a greater weight (p < .001) for food acquisition. Sugary drinks were the most widely acquired in all social and school levels. The lowest social level is the one who acquires the most cereals, fats, sugars and legumes, while for high school levels animal foods and processed meats are the ones most frequently acquired.
Conclusion:
the socioeconomic level has a great weight in the acquisition and variety of foods, although this does not mean that foods obtained are the healthiest. Therefore, public policies are urgently required in favor of nutritional education at all school levels, which promote the purchase of healthy foods and compete with commercial advertising strategies.
... In addition, poor nutrition has severe consequences for the immune response in the elderly and it becomes even more serious health the same when associated with typical immunosenescence frame. Thus, the vicious cycle between nutritional deficiencies and infections related to immunosenescence is a very vulnerable condition in the population above 60 years old (21). ...
The aim of this article is to objectively summarize the report of the European Scientific Committee in charge of updating the algorithm underlying the front-of-pack nutritional label Nutri-Score. It described the methodology used and the priorities established, the scientific rational and the different scenarios tested, the proposed modifications and their impact on the different food groups concerned. The Scientific Committee considered that its current algorithm works globally well, but has introduced some improvements. Modifications recommended allow to correct some of its identified limits: classification of oils, fatty fish, whole grain products, nuts, cheeses, higher penalization of very sugary or very salty foods, sweet dairy products, composite products, red meat… while maintaining the overall consistency of the system and the classification of the products. The update of the Nutri-Score algorithm permits a better alignment between the Nutri-Score classifications and nutritional recommendations disseminated in the different European countries that have adopted it.
... Vitamins and trace elements are defined as epigenetic modifiers [22]. High mortality and morbidity rates among patients with NCDs in the world have been attributed to disorders in the immune system and malnutrition [10,23,24,25]. Therapy with micronutrients in patients with NCDs is used to improve nutritional status, strengthen immune system, and decrease circulatory inflammatory cytokines via epigenetic modification [26,27,28,29,30]. ...
Background: Non-communicable diseases (NCDs) have received more attention because of high prevalence and mortality rate. Besides genetic and environmental factors, the epigenetic abnormality is also involved in the pathogenesis of NCDs. Methylation of DNA, chromatin remodeling, modification of histone, and long non-coding RNAs are the main components of epigenetic phenomena. Methodology: In this review paper, the mechanistic role of vitamins and dietary patterns on epigenetic modification was discussed. All papers indexed in scientific databases, including PubMed, Scopus, Embase, Google Scholar, and Elsevier were searched during 2000 - 2021 using, vitamins, diet, epigenetic repression, histones, methylation, acetylation, and NCDs as keywords. Results: The components of healthy dietary patterns like Mediterranean and dietary approaches to stop hypertension diets have a beneficial effect on epigenetic hemostasis. Both quality and quantity of dietary components influence epigenetic phenomena. A diet with calorie deficiency in protein content and methyl-donor agents in a long time, with a high level of fat, disrupts epigenetic hemostasis and finally, causes genome instability. Also, soluble and insoluble vitamins have an obvious role in epigenetic modifications. Most vitamins interact directly with methylation, acetylation, and phosphorylation pathways of histone and DNA. However, numerous indirect functions related to the cell cycle stability and genome integrity have been recognized. Conclusion: Considering the crucial role of a healthy diet in epigenetic homeostasis, adherence to a healthy dietary pattern containing enough levels of vitamin and avoiding the western diet seems to be necessary. Having a healthy diet and consuming the recommended dietary level of vitamins can also contribute to epigenetic stability.
... Various factors like physical activity, health and psychological status of the older people can influence the nutritional status. Meydani et al., felt that the nutritional status, particularly in developing world is poor and preventive measures should be planned ahead in order to prevent certain disease conditions [4][5][6][7] . Elderly people in low socio-economic groups are at higher risk of poor dietary intake [8,9] . ...
Adult's food intake behaviours is particularly important in the context of food insecurity. Since there has been population studies indicating increased risk of overweight and obesity among those who are food insecured. The disparity between the food supply and the intake of foods and nutrients has been getting larger ever since 1970's. BMI, a widely used measure of nutritional status is the ratio of weight to height measurements. As far as food security is concerned, the adequacy of the supply of nutrients, in particular energy and protein are available to the population. Objective: i) To study the anthropometric measurements and the association between BMI and nutrient intake of the adults. Methodology: Demographic data, nutrient intake (diary technique) and anthropometric measurements (height, weight, MUAC, waist and hip circumferences) were obtained using standard procedures. 350 couples aged 35-60 yrs formed the study population. Results: All were educated, regardless of occupation with varied kind of jobs. Both men and women had normal BMI however WHR was higher indicating central obesity (1.00±0.97 and 0.99±0.137); for males and females respectively. Mean nutrient (Energy) intakes of male and females partners are: 2042 ±369 ±.92 and 1875± 511.090kcals; Compared to RDA, intake of all nutrients except fat and calcium were markedly low and there was a extremely significant difference. Energy bears a positive association of micronutrients. Although the association between nutrient intake and BMI did not exhibit statistical difference. Conclusion: Nutrient intakes of men and women were essentially similar and their BMI tend to be overweight.
... Because NCDs are the world's leading cause of death, patients receive micronutrient therapy strategies to treat undernutrition, improve immunity, and prevent infection [10,11]. At the UN High-Level Meeting on the Prevention and Control of Non-Communicable Diseases, held in New York, USA in September 2011, prevention strategies for NCDs have already been addressed with a view to prenatal nourishment, improving diet and nutrients, and preventing undernutrition and infections. ...
Purpose of review:
The highly infectious transmissible disease, the novel SARS-CoV-2, causing the coronavirus disease (COVID-19), has a median incubation time of 5 to 15 days. The symptoms vary from person to person and many are "hidden carriers." Few people experience immediate reaction and even death within 48 h of infection. However, many show mild to chronic symptoms and recover. Nevertheless, the death rate due to COVID-19 transmission is high especially among patients with non-communicable diseases. The purpose of this review is to provide evidence to consider vitamins as epigenetic modifiers to enhance immunity and reduce inflammatory response in COVID-19 patients with non-communicable diseases.
Recent findings:
Clinical evidence has suggested the risk of getting infected is high among individuals with non-communicable diseases such as cardiovascular disease, type-2 diabetes, cancer, acute respiratory distress syndrome, and renal disease, as well as the elderly with high mortality rate among the cohort. The impact is due to an already compromised immune system of patients. Every patient has a different response to COVID-19, which shows that the ability to combat the deadly virus varies individually. Thus, treatment can be personalized and adjusted to help protect and combat COVID-19 infections, especially in individuals with non-communicable diseases. Based on current published scientific and medical evidence, the suggestions made in this article for combination of vitamin therapy as epigenetic modifiers to control the unregulated inflammatory and cytokine marker expressions, further needs to be clinically proven. Future research and clinical trials can apply the suggestions given in this article to support metabolic activities in patients and enhance the immune response.
... In addition, poor nutrition has severe consequences for the immune response in the elderly and it becomes even more serious health the same when associated with typical immunosenescence frame. Thus, the vicious cycle between nutritional deficiencies and infections related to immunosenescence is a very vulnerable condition in the population above 60 years old (21). ...
Introduction: Life expectancy is increasing and becoming a characteristic phenomenon of developed countries and, increasingly, of developing countries, such as Brazil. The aging process causes changes of some physiological functions such as loss of smell, taste, loss of appetite, among other things that end up changing the food intake of these individuals. Objectives: This study aimed to assess food consumption of the young and long-lived elderly in a city in southern Brazil. Methods: A cross-sectional survey conducted through home visits in Palmeira das Missões - RS, Brazil. The sociodemographic, anthropometrical and dietary data were collected through questionnaires and 24-hour recall. The adequacy of nutrients was assessed according to the Dietary Reference Intakes. Data were analyzed using SPSS 18.0 software. Results: The study included 424 older adults, 84,4% (n = 358) aged less than 80 years old and 15,6% (n = 66) older than 80. The intake of energy and protein was insufficient for both young elderly and the oldest. The consumption of vitamins and minerals has been insufficient in all seniors except for iron, which presented an excessive intake. There was a statistically significant difference between the elderly and oldest only for the consumption of lipids and vitamin B12. Conclusion: The majority of studies with elderly corroborate the results found in this article. An inadequate intake of nutrients can develop nutritional deficiencies, and consequently it can result in physiological and pathological changes which would compromise the functional capacity of the elderly. Energy consumption was insufficient and macronutrients were inadequate, both for the young elderly as for the oldest. Additionally, the consumption of vitamins and minerals was insufficient to everyone except the iron, which presented excessive intake for young and oldest elderly.
... In addition, poor nutrition has severe consequences for the immune response in the elderly and it becomes even more serious health the same when associated with typical immunosenescence frame. Thus, the vicious cycle between nutritional deficiencies and infections related to immunosenescence is a very vulnerable condition in the population above 60 years old (21). ...
Introducción: la esperanza de vida está aumentando y convirtiéndose en un fenómeno característico de los países desarrollados y, cada vez más, de los países en desarrollo, como Brasil. El proceso de envejecimiento produce cambios en algunas funciones fisiológicas, como la pérdida del olfato o gusto o pérdida de apetito, entre otros, que terminan alterando la ingesta de alimentos de estos individuos.Objetivos: este estudio tuvo como objetivo evaluar el consumo de alimentos de los ancianos y de los ancianos más longevos en una ciudad del sur de Brasil.Métodos: un estudio transversal realizado mediante visitas a domicilio en Palmeira das Missões - RS, Brasil. Los datos sociodemográficos, antropométricos y dietéticos fueron recogidos a través de cuestionarios y recordatorio de 24 horas. La adecuación de nutrientes se evaluó de acuerdo con las ingestas de referencia en la dieta. Los datos fueron analizados utilizando el software SPSS 18.0.Resultados: el estudio incluyó a 424 adultos mayores, el 84.4% (n = 358) de ellos menores de 80 años y el 15.6% (n = 66) con más de 80 años. La ingesta de energía y proteínas fue insuficiente tanto para jóvenes adultos como para los más ancianos. El consumo de vitaminas y minerales ha sido insuficiente en todos los adultos mayores a excepción del hierro, que presentaba una ingesta excesiva. Hubo una diferencia estadísticamente significativa entre las personas de edad y mayores sólo en cuanto al consumo de lípidos y vitamina B12. Conclusión: la mayoría de los estudios con personas mayores corrobora los resultados obtenidos en este artículo. Una ingesta inadecuada de nutrientes puede dar lugar a deficiencias nutricionales y, por lo tanto, a cambios fisiológicos y patológicos que pondrían en peligro la capacidad funcional de los ancianos. El consumo de energía y de macronutrientes resultó insuficiente tanto para los ancianos como para los ancianos más longevos. Además, el consumo de vitaminas y minerales
... It is encouraging that developing countries showed an increase in research and number of articles published, yet the 10 developed countries that published the most articles 7 Older adults are more prone to contracting noncommunicable diseases (diabetes mellitus, cardiovascular diseases, cancer, and chronic respiratory diseases), infectious diseases, and malnutrition than younger adults. [8][9][10] These diseases and conditions are a great burden on the healthcare and economic systems of developing countries. Therefore, the public health system and research must place a strong focus on measures for healthy aging in the elderly population. ...
... Its repair or prevention effects have been attributed to the presence of antioxidants, mainly contained in plant foods such as fruit, vegetables, whole grains, nuts and seeds. Several studies have indicated that vitamin E and/or coenzyme Q 10 supplementation can improve antioxidant activity of cell membranes in the elderly [24,25,120]. ...
Aging is a condition which favors the development of atherosclerosis, which has been associated with a breakdown in repair processes that occurs in response to cell damage. The dysregulation of the biological systems associated with aging are produced partly through damage which accumulates over time. One major source of this injury is oxidative stress, which can impair biological structures and the mechanisms by which they are repaired. These mechanisms are based on the pathogenesis of endothelial dysfunction, which in turn is associated with cardiovascular disease, carcinogenesis and aging. The dependent dysfunction of aging has been correlated with a reduction in the number and/or functional activity of endothelial progenitor cells, which could hinder the repair and regeneration of the endothelium. In addition, aging, inflammation and oxidative stress are endogenous factors that cause telomere shortening, which is dependent on oxidative cell damage. Moreover, telomere length correlates with lifestyle and the consumption of a healthy diet. Thus, diseases associated with aging and age may be caused by the long-term effects of oxidative damage, which are modified by genetic and environmental factors. Considering that diet is a very important source of antioxidants, in this review we will analyze the relationship between oxidative stress, aging, and the mechanisms which may be involved in a higher survival rate and a lower incidence of the diseases associated with aging in populations which follow a healthy diet.
... Energy and nutrient supplies are especially important for the immune system because its individual components are characterized by high turnover rates, leading to a higher Substrate requirement compared to most other body Systems. Only if all essential mitrients are supplied in appropriate amounts can the biochemical and cellular mechanisms that provide tlie basis of the immune system work optimally [2], Therefore, it is not surprising that the immunocompetence of an organism is significantly influenced by its intake of micronutrients (vitamins, minerals, and certain fatty acids) [3][4][5][6][7][8][9], In contrast, tlie activity of the immune system can affect nutrient Status, äs can be observed in immune diseases, including acquired immunodeficiency syndrome (AIDS) [10][11][12] and rheumatoid arthritis [13][14][15]. Accordingly, dietary factors have become increasingly important in the Potential treatment of imiminoiogical inflammatory diseases [16][17][18][19][20]. ...
As elements of the antioxidant system, cofactors of enzymes, components of transcription factors, and epigenetic modulators, micronutrients, such as vitamins and trace elements, influence various metabolic processes that are directly associated with immune functions. Specifically, the vitamins C and D have been shown to have significance immune function. Therefore, the objective of this review is to elucidate interactions between micronutrients and the immune system. In the initial section of this review, we present a general overview of interactions between the immune system and micronutrients, with a focus on the immunobiologically relevant functions of vitamin C. Immune competent cells accumulate vitamin C against a concentration gradient, with a close relationship between vitamin C supply and immune cell activity, especially phagocytosis activity and T-cell function. Accordingly, one of the consequences of vitamin C deficiency is impaired resistance to various pathogens, while an enhanced supply increases antibody activity and infection resistance.
... 17,29,31 Protein was derived mainly from plants; animal protein and dairy intake were very low. 10,13,38 Among elderly women living in underserved areas of Nairobi, Kenya, a mean of only 6 g/d was reported for animal protein. 17,45 About a quarter (27%) of the elderly in Zimbabwe ate a protein-containing meal less than once a week, and 17.6% of black South Africans had intakes that were less than 66% of Dietary Reference Intakes (DRI), the lower reference value for adequate intake. ...
The proportion of the population that is > or = 60 years of age in sub-Saharan Africa (SSA) is increasing rapidly and is likely to constrain healthcare systems in the future. Nevertheless, the elderly are not a health policy priority for African countries. This paper reviews the nutritional and health status of older adults in SSA and their determinants. Literature was abstracted through the Medline, Google Scholar, and Dogpile databases using the following search terms: sub-Saharan Africa, older adults, nutrition, health. Findings showed that up to half (6-48%) of elderly Africans in SSA are underweight and almost a quarter (2.5-21%) are overweight, while 56% of older South Africans are obese. Low-quality diets contribute to poor nutritional status. Poverty, HIV/AIDS, and complex humanitarian emergencies are major determinants of undernutrition. Effective interventions need to consider socioeconomic, health, and demographic factors; social pensions may be the most cost-effective option for improving the health and nutritional status of the elderly in SSA.
... Extensive research demonstrates that diet is crucial to maintaining an optimal immune function [1,2]. During food digestion and nutrient absorption, the small intestine is exposed to a large variety of environmental antigens [3]. ...
Gut-associated lymphoid tissue (GALT) maintains mucosal homeostasis by counteracting pathogens and inducing a state of nonresponsiveness when it receives signals from food antigens and commensal bacteria. We report for the first time the influence of continuous cocoa consumption on GALT function in rats postweaning. Weaned Wistar rats were fed cocoa-enriched diets (4% or 10% food intake) for 3 weeks. The function of the primary inductive sites of GALT, such as Peyer's patches (PP) and mesenteric lymph nodes (MLN), was evaluated through an analysis of IgA-secretory ability and lymphocyte composition (T, B and natural killer cells), activation (IL-2 secretion and IL-2 receptor alpha expression) and proliferation. T-helper effector cell balance was also established based on cytokine profile (interferon gamma, IL-4 and IL-10) after mitogen activation. A 10% cocoa intake induced significant changes in PP and MLN lymphocyte composition and function, whereas a 4% cocoa diet did not cause significant modifications in either tissues. Cocoa diet strongly reduced secretory IgA (S-IgA) in the intestinal lumen, although IgA's secretory ability was only slightly decreased in PP. In addition, the 10% cocoa diet increased T-cell-antigen receptor gammadelta cell proportion in both lymphoid tissues. Thus, cocoa intake modulates intestinal immune responses in young rats, influencing gammadelta T-cells and S-IgA production.
Since the ongoing coronavirus disease 2019 (COVID-19) pandemic is linked to chronic inflammation, people with initial lower inflammatory status could have better outcomes from exposure to this disease. Because dietary habits are one of the most important modifiable risk factors for inflammation, identification of dietary components associated with inflammation could play a significant role in controlling or reducing the risk of COVID-19. We investigated the inflammatory potential of diets consumed by African American (AA) and Caucasian American (CA) women of childbearing age (n = 509) who are at high risk for exposure to COVID-19 by being residents of Birmingham, Alabama, a city severely affected by this pandemic. The overall pro- and anti- inflammatory scores were calculated using dietary intake data gathered using Block food frequency questionnaire. The proinflammatory potential of diets consumed by AAs was significantly higher compared to CAs. Several anti- and proinflammatory nutrients and food groups consumed differed by race. With consumption of a greater number of antioxidants and B-vitamins, CAs switched toward an anti-inflammatory score more effectively than AAs while AAs performed better than CAs in improving the anti-inflammatory score with the consumption of a greater number of minerals and vitamin D. Effective race-specific dietary modifications or supplementation with nutrients identified will be useful to improve proinflammatory diets toward anti-inflammatory. This approach could aid in controlling the current COVID-19 pandemic and future pandemics of a similar nature in women at risk for exposure.
Vitamin C (ascorbate) is maintained at high levels in most immune cells and can affect many aspects of the immune response. Here, we evaluated the effect of vitamin C supplementation on the immune response to Plasmodium yoelii 17XL (P. yoelii 17XL) infection in BALB/c mice. Two orally administered doses (25 mg/kg/day and 250 mg/kg/day) of vitamin C significantly reduced levels of parasitemia during the early stages of P. yoelii 17XL infection. The numbers of activated Th1 cells and macrophages in the groups receiving vitamin C supplementation were both higher than those in the untreated group. Meanwhile, vitamin C administration reduced the levels of tumor necrosis factor α secreted by splenocytes. Vitamin C also regulated the protective anti-malarial immune response by increasing the number of plasmacytoid dendritic cells, as well as the expression of dendritic cell maturation markers, such as major histocompatibility complex class II and cluster of differentiation 86. In conclusion, the doses of vitamin C (25 mg/kg/day, 250 mg/kg/day) during the early stages of malaria infection may better enhance host protective immunity, but have no dose dependence.
One hundred and twenty elderly farmers aged 60-100 years living in Abanla village of Idi-Ayunre Local Government area of Oyo State, Nigeria, were assessed for dietary and urinary Zinc excretion. Dietary zinc intakes were measured from meals consumed over a two day period. The dietary zinc intake of the elderly male and female farmers was similar(P>0.05).The mean daily zinc intake of 12.46+/-1.45mg for males and 11.82+/-2.61mg for females appeared marginally adequate compared to the recommended dietary allowance (RDA). The respondents may be deficient in zinc because there was lack of or low intake of rich sources of zinc such as beef, egg, and oyster. The diet of the elderly people were also predominantly of plant origin. However, the urinary zinc excretion was within acceptable ranges. The males excreted significantly more (P<0.05) urinary zinc than the females (3.01+/-2.21g/8 hours and 2.00 +/-1.40 g/8 hours respectively). No correlation existed between age and urinary zinc excretion (r=0.029, n=90). Nutrition education should be promoted throughout life especially during adolescent period when food habits are being formed. Regular medical check-up should also be encouraged so that early detection and correction of infirmities would reduce age onset or pathological conditions.
It has been known that, immune functions decline with age. The studies clearly demonstrate that under-nutrition contributes to the decline of immune function with aging. Physical, physiological, psychological and socio-economical factors may affect nutritional status and nutrient intakes of elderly. Frequently, inadequate intake of some antioxidant nutrients such as vitamin E, vitamin C, beta-carotene and zinc may have effect on immune function in elderly. Unhealthy nutrition and age related dysregulation of immune system contribute to the increased incidence of infectious, inflammatory, and neoplastic diseases. In this review, the relation between immune senescence and antioxidant nutrients were discussed.
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.
Nutraceuticals, including dietary supplements and functional foods, are a $152 billion world market. The percentage of those
aged 65 years and older using nutraceutical products is higher than for any other age group and has doubled in recent years.
Aging is associated with decreased immunity, increased morbidity and mortality resulting from infectious agents, and poor
nutritional status. Deficiencies in vitamin E, vitamin B6, folate, zinc, and selenium, for example, are particularly common, and deficits in these micronutrients have been reported
to negatively influence immunity. Thus, if nutraceutical products can improve micronutrient status, the regular use of nutraceuticals
by the elderly population may provide an opportunity to enhance immunity in this at-risk population. Results from human clinical
trials evaluating the use of nutraceuticals to support immune restoration in the elderly, however, have been largely inconsistent.
Additional clinical trials using consistent outcome measures are needed, which will require a cooperative commitment from
the nutraceutical industry and academia.
Immunization of young children with the oral inactivated whole cell cholera vaccine Dukoral((R)) containing recombinant cholera toxin B subunit (CTB) induces antibody responses which can be further enhanced by zinc supplementation. We have investigated if immunization with the cholera vaccine induces specific T-cell responses in young children and also whether zinc supplementation influences these responses. Bangladeshi children (10-18 months old) received vaccine alone, vaccine together with zinc supplementation or only zinc. T-cell blast formation indicating a proliferative response was analyzed by the flow cytometric assay of cell-mediated immune response in activated whole blood (FASCIA) and cytokines were measured by ELISA. Stronger T-cell responses were detected if a modified CTB molecule (mCTB) with reduced binding to GM1 ganglioside was used for cell stimulation compared to normal CTB. After vaccination, CD4+ T cells responded to mCTB with significantly increased blast formation (P<0.01) and IFN-gamma production (P<0.05) compared to before vaccination. No responses to mCTB were detected in children receiving zinc alone (P>0.05). The IFN-gamma production was significantly higher (P<0.01) but the blast formation comparable (P>0.05) in children receiving zinc plus vaccine compared to in children receiving vaccine alone. The vibriocidal antibody responses induced by the vaccine were also significantly higher in children receiving zinc supplementation (P<0.001). Our results thus show that oral cholera vaccination induces a Th1 T-cell response in young children, and that the IFN-gamma as well as the vibriocidal antibody responses can be enhanced by zinc supplementation.
This study assessed trends in survival to old age and identified the factors associated with longevity among the elderly (age > or = 65 years).
Cohort analysis of demographic surveillance data.
The study was conducted in the Butajira Rural Health Programme Demographic Surveillance Site in Ethiopia. Using data collected between 1987 and 2004, the probability of survival to 65 years and remaining life expectancy for women and men aged 65 years were computed. Cox regression analysis was used to assess survival by different factors.
Although the elderly represented 3% of the population, their person-time contribution increased by 48% over the 18-year period. Less than half reached 65 years of age, with remaining life expectancy at 65 years ranging from 15 years in rural men to 19 years in urban women. Rural residence, illiteracy and widowhood were associated with lower survival adjusted for other factors, whereas gender did not show a significant difference. However, the effect of these factors differed between men and women, as demonstrated by survival curves and Cox regression. Widowhood [hazard ratio (HR) 2.02, 95% confidence interval (CI) 1.59-2.57] and illiteracy (HR 2.26, 95% CI 1.86-2.73) affected males to a greater extent than females, and rural residence was associated with poorer female survival (HR 1.68, 95% CI 1.55-1.83).
The number of elderly people is increasing in Ethiopia, with the chance of survival into older age being similar between men and women and approaching that in developed countries. However, rural women and illiterate women and men, particularly widowers, are disadvantaged in terms of survival.
The purpose of this study is to develop the GPM-K and test the validity and reliability of it. GPM-K is a multidimensional pain assessment instrument for older adults. One hundred twenty-one community-dwelling old adults aged 65 and older who expressed chronic pain were included. They completed GPM-K. The Korean version of the Brief Pain Inventory (BPI-K), Korean Mini-Mental State Examination (K-MMSE), Geriatric Depression Scale Short Form Korean version (GDSSF-K), Pain Management Index (PMI), and Elderly Life Stress Index (ELSI) were used to further validate the GPM-K. A standardized Cronbach's alpha was 0.92, and average inter-item correlation was 0.32. Of those, who repeated the GPM-K within 2-4 weeks (n=32), Pearson's r correlation of test-retest reliability was statistically significant (r=0.640). Correlation coefficient was highly significant between the GPM-K and mean pain severity of the BPI-K (r=0.726, p<0.001), and between the GPM-K and mean pain interference of the BPI-K (r=0.698, p<0.001), as well. The GPM-K was correlated with the GDSSF-K (r=0.256), the ELSI (r=0.312) and the PMI (r=-0.509). The GPM-K is a valid and useful instrument to assess pain and its related factors for the Korean older adults.
The free radical theory of aging suggests that damage caused by oxidative stress leads to impaired physiologic functions. This damage is stemmed by an adequate antioxidant status, which minimizes the occurrence of infection, thus potentially playing a role in improving nutritional status. The role played by genetic factors remains unknown.
The aim of this study was to investigate whether a single nucleotide polymorphism (SNP) of a gene coding for endogenous antioxidant enzymes could influence either nutritional status or renutrition process in an elderly population.
Nutritional and inflammatory status were studied in 77 elderly outpatients and in 99 malnourished elderly inpatients over 6 wk of health care treatment. Renutrition efficiency was evaluated with use of the ratio between initial transthyretinemia and 6-wk variation. A genetic study was performed on superoxide dismutase (Ala-9Val), glutathione peroxidase (Pro197Leu), and catalase (from promoter to the first intron).
Among the SNPs studied, the G-844A, A-89T, and C-20T catalase SNPs could each be markers predicting renutrition efficiency. These catalase mutant alleles were associated with a lower efficiency of renutrition in malnourished elderly subjects, regardless of initial nutritional and inflammatory status. Genotyping one of these catalase SNPs could make it possible to identify a high-risk subpopulation of mutant allele carriers within the elderly polypathological population.
In a malnutrition setting, this subpopulation should be given personalized health care, including a strengthened refeeding program. Thus, catalase genotyping could enable earlier recovery of satisfactory nutritional status and thus avoid the consequences of malnutrition, which are especially deleterious in the elderly.
There is a growing recognition that nutrition influences immune function not only in young populations with severe malnutrition and a high incidence of infectious disease but also in groups with relatively mild or single nutrient deficiencies (Chandra and Chandra, 1986; James and Makinodan, 1984). Several comprehensive reviews in this area have been published recently (Stinnett, 1983; Gershwin et al., 1985; Fernandes, 1984; Beisel, 1982; Keusch et al., 1983). The elderly represent a large and expanding group with a significant number of individuals noted to possess poor nutritional status in the face of potentially increasing nutrient requirements and decreasing immunocompetence. Thus, as malnutrition impairs immunity, nutritional problems may contribute to declining immunity in old age, and appropriate dietary intervention may improve immune responsiveness and reduce the burden of illness in the elderly. Recently, attention has been focused on the possibility of utilizing selective nutritional manipulations to regulate the aberrant response of diseases associated with immune disorders (Chandra, 1985; Corman, 1985).
Background
Antioxidant supplementation is thought to improve immunity and thereby reduce infectious morbidity. However, few large trials in elderly people have been conducted that include end points for clinical variables.Objective
To determine the effects of long-term daily supplementation with trace elements (zinc sulfate and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) on immunity and the incidence of infections in institutionalized elderly people.Methods
This randomized, double-blind, placebo-controlled intervention study included 725 institutionalized elderly patients (>65 years) from 25 geriatric centers in France. Patients received an oral daily supplement of nutritional doses of trace elements (zinc and selenium sulfide) or vitamins (beta carotene, ascorbic acid, and vitamin E) or a placebo within a 2×2 factorial design for 2 years.Main Outcome Measures
Delayed-type hypersensitivity skin response, humoral response to influenza vaccine, and infectious morbidity and mortality.Results
Correction of specific nutrient deficiencies was observed after 6 months of supplementation and was maintained for the first year, during which there was no effect of any treatment on delayed-type hypersensitivity skin response. Antibody titers after influenza vaccine were higher in groups that received trace elements alone or associated with vitamins, whereas the vitamin group had significantly lower antibody titers (P<.05). The number of patients without respiratory tract infections during the study was higher in groups that received trace elements (P=.06). Supplementation with neither trace elements nor vitamins significantly reduced the incidence of urogenital infections. Survival analysis for the 2 years did not show any differences between the 4 groups.Conclusions
Low-dose supplementation of zinc and selenium provides significant improvement in elderly patients by increasing the humoral response after vaccination and could have considerable public health importance by reducing morbidity from respiratory tract infections.
The effect of vitamin B-6 deficiency on immune response was studied in eight healthy elderly adults. The protocol consisted of a 5-d baseline (BL) period; a vitamin B-6-depletion period of less than or equal to 20 d; three stages of vitamin B-6-repletion, each lasting 21 d; and a 4-d final phase. The amounts of vitamin B-6 ingested during the different phases of the study were 3.00, 15.00, 22.50, and 33.75 micrograms.kg body wt-1.d-1, respectively. During the final phase the subjects ingested 50 mg vitamin B-6/d. Fasting blood was collected at the end of each period. Vitamin B-6 depletion significantly decreased percentage and total number of lymphocytes, mitogenic responses of peripheral blood lymphocytes to T- and B-cell mitogens, and interleukin 2 production. These indices returned to BL values after the third vitamin B-6-repletion period, when the total vitamin B-6 intakes were 1.90 +/- 0.18 mg/d for women and 2.88 +/- 0.17 mg/d for men. Vitamin B-6 deficiency impairs in vitro indices of cell-mediated immunity in healthy elderly adults. This impairment is reversible by vitamin B-6 repletion.
The effect of vitamin E supplementation on the immune response of healthy older adults was studied in a double-blind, placebo-controlled trial. Subjects (n = 32) resided in a metabolic research unit and received placebo or vitamin E (800 mg dl-alpha-tocopheryl acetate) for 30 d. Alpha-tocopherol content of plasma and peripheral blood mononuclear cells (PBMCs), delayed-type hypersensitivity skin test (DTH), mitogen-stimulated lymphocyte proliferation, as well as interleukin (IL)-1, IL-2, prostaglandin (PG) E2, and serum lipid peroxides were evaluated before and after treatment. In the vitamin E-supplemented group 1) alpha-tocopherol content was significantly higher (p less than 0.0001) in plasma and PBMCs, 2) cumulative diameter and number of positive antigen responses in DTH response were elevated (p less than 0.05), 3) IL-2 production and mitogenic response to optimal doses of concanavalin A were increased (p less than 0.05), and 4) PGE2 synthesis by PBMCs (p less than 0.005) and plasma lipid peroxides (p less than 0.001) were reduced. Short-term vitamin E supplementation improves immune responsiveness in healthy elderly individuals; this effect appears to be mediated by a decrease in PGE2 and/or other lipid-peroxidation products.
The effect of pyridoxine supplementation on lymphocyte responsiveness was investigated in 15 persons aged 65-81 y. Eleven subjects received 50 mg/d pyridoxine HCl (PN). Four subjects received a placebo. Lymphocyte proliferation to T and B cell mitogens, lymphocyte subpopulations with monoclonal antibodies, and plasma pyridoxal 5'-phosphate (PLP) were measured before and after 1 and 2 mo of supplementation. After 1 and 2 mo plasma PLP levels increased by 195 +/- 88 nM and 201 +/- 84 nM, respectively, in subjects receiving PN. With PN supplementation, lymphocyte proliferation increased significantly in response to phytohemagglutinin (p less than 0.01), pokeweed mitogen (p less than 0.01), and Staphylococcus aureus (Cowain I) (p less than 0.05). For PN-treated subjects with low presupplement plasma PLP levels, lymphocyte blastogenesis also increased significantly (p less than 0.01) in response to concanavalin A. Percentages of T3+ and T4+ but not T8+ cells increased significantly (p less than 0.05) in PN-treated subjects. These results suggest that improving vitamin B-6 status is important in stimulating immunocompetence in the elderly.
The oxidant-antioxidant balance is an important determinant of immune cell function, including maintaining the integrity and functionality of membrane lipids, cellular proteins, and nucleic acids and controlling signal transduction and gene expression in immune cells. Optimal amounts of antioxidants are needed for maintenance of the immune response across all age groups. This need might be more critical, however, in aged persons. Age-associated dysregulation of immune response, particularly of T cell-mediated function, is well documented. The well-known age-related increase in free radical formation and lipid peroxidation contributes, at least in part, to this phenomenon. We summarize animal and human studies undertaken by ourselves as well as other investigators on the effects of antioxidants, vitamin E, beta-carotene, and glutathione on the immune response of aged persons. The underlying mechanisms for the antioxidant nutrients' effects as well as their health implications for aged persons are discussed.
To investigate the relationship between age and energy expenditure, resting metabolic rate (RMR) and diet-induced thermogenesis (DIT; for 180 min after a 1.3-MJ meal) were measured by indirect calorimetry in 56 young and 103 elderly subjects. In addition, the influence of body composition, body-fat distribution, and physical activity level on this relationship was studied. RMR was significantly lower in elderly (3.98 +/- 0.46 and 3.33 +/- 0.39 kJ/min for men and women, respectively) than in young (5.29 +/- 0.53 and 4.08 +/- 0.33 kJ/min for men and women, respectively) subjects, which persisted after adjustment for body composition. DIT was significantly lower in older than in younger men (126 +/- 27 vs 154 +/- 34 kJ/180 min) but not in women (111 +/- 26 vs 115 +/- 25 kJ/180 min). The difference in men disappeared after adjustment for body composition. No clear relation between physical activity level and RMR or DIT was observed. These results demonstrate a relationship of age per se with RMR but not with DIT.
A placebo-controlled double-blind trial of the effects of daily micronutrient supplements on circulating vitamin and trace metal concentrations and delayed-hypersensitivity skin test (DHST) responses was conducted. Subjects, aged 59-85 y, were randomly assigned to placebo (n = 27) or micronutrient (n = 29) treatment groups. DHST and circulating concentrations of nine micronutrients were measured before and after 6 and 12 mo of micronutrient ingestion. For the micronutrient group, there were statistically significant increases at 6 and/or 12 mo in the mean serum concentrations of ascorbate, beta-carotene, folate, vitamin B-6, and alpha-tocopherol. There was a significant increase at 12 mo in the number of subjects in the placebo group with one or more low concentrations. DHST responses to a panel of seven recall antigens were significantly increased at 12 mo in the micronutrient group but not the placebo group. This study demonstrates that daily supplementation with low-to-moderate doses of micronutrients can prevent low concentrations of some micronutrients and can improve DHST responses in healthy, independently living older adults.
According to the final 1994 data released by the National Center for Health Statistics, life expectancy at birth in the United States for all races and both sexes is 76 yr (1). Future projections indicate that increases in the population sector of individuals age 65 yr and over will continue into the second millennium. Age-associated changes in physiological, psychological, social, and economic factors may adversely affect the nutritional and immunological status of older individuals; these changes are often reflected in poor health and reduced quality of life. Incidence of infections and diseases such as cancer, atherosclerosis, and autoimmunity have been shown to increase with age.
Objective.
—To determine whether long-term supplementation with vitamin E enhances in vivo, clinically relevant measures of cell-mediated immunity in healthy elderly subjects.
Design.
—Randomized, double-blind, placebo-controlled intervention study.
Setting and Participants.
—A total of 88 free-living, healthy subjects at least 65 years of age.
Intervention.
—Subjects were randomly assigned to a placebo group or to groups consuming 60, 200, or 800 mg/d of vitamin E for 235 days.
Main Outcome Measures.
—Delayed-type hypersensitivity skin response (DTH); antibody response to hepatitis B, tetanus and diphtheria, and pneumococcal vaccines; and autoantibodies to DNA and thyroglobulin were assessed before and after supplementation.
Results.
—Supplementation with vitamin E for 4 months improved certain clinically relevant indexes of cell-mediated immunity in healthy elderly. Subjects consuming 200 mg/d of vitamin E had a 65% increase in DTH and a 6-fold increase in antibody titer to hepatitis B compared with placebo (17% and 3-fold, respectively), 60-mg/d (41% and 3-fold, respectively), and 800-mg/d (49% and 2.5-fold, respectively) groups. The 200-mg/d group also had a significant increase in antibody titer to tetanus vaccine. Subjects in the upper tertile of serum α-tocopherol (vitamin E) concentration (>48.4 μmol/L [2.08 mg/dL]) after supplementation had higher antibody response to hepatitis B and DTH. Vitamin E supplementation had no effect on antibody titer to diphtheria and did not affect immunoglobulin levels or levels of T and B cells. No significant effect of vitamin E supplementation on autoantibody levels was observed.
Conclusions.
—Our results indicate that a level of vitamin E greater than currently recommended enhances certain clinically relevant in vivo indexes of T-cell-mediated function in healthy elderly persons. No adverse effects were observed with vitamin E supplementation.
Objective.—
Diarrhea is an important cause of death among young children in both developing and developed countries, but little is known about diarrheal deaths among adults. In this study, we examined trends in diarrheal deaths among all age groups in the United States.Design/Setting/Participants.—
We reviewed national mortality data compiled by the National Center for Health Statistics, Hyattsville, Md, which consist of information from all death certificates filed in the United States for the period 1979 through 1987. A death for which diarrhea was listed as an immediate or underlying cause was considered a "diarrheal death" and included in the analysis.Results.—
We found that 28 538 persons died of diarrhea cited as either an immediate or the underlying cause of death during the 9-year period. A majority of diarrheal deaths occurred among the elderly (older than 74 years of age, 51%), followed by adults 55 to 74 years of age (27%), and young children ( younger than 5 years of age, 11%). For the elderly, adjusted risk factors for dying of diarrhea included being white, female, and residing in a long-term care facility. Only the elderly and young children had clear, distinct winter peaks of diarrheal deaths, suggesting that the diarrhea may, in part, be infectious in origin.Conclusion.—
For the elderly, more directed studies of those at risk, such as nursing home residents, are needed to determine if oral rehydration therapy, vaccines, or other preventive measures might benefit this population.(JAMA. 1991;265:3280-3284)
Over the past five years, the American public has witnessed a flurry of interest in “character” and “character or moral education.” In 1992, William Kilpatrick wrote a book that attracted widespread attention, Why Johnny Can't Tell Right from Wrong: Moral Illiteracy and the Case for Character Education. A year later, William Bennett's best-selling anthology of remedial readings appeared, The Book of Virtues. More recently, Gertrude Himmelfarb published a book on the Victorian golden age of morals. At the same time, within the educational field, a subprofession of consultants devoted to character work has aimed to affect schooling at the elementary and secondary levels. As early as the mid-1970's, theologians and ethicists began discussing the idea of character, taking their cue from Stanley Hauerwas. Common to all of these writers is the belief that character has a necessary tie to religion and democracy.
Splenocytes from young adult or old C57BL/6NNia mice were stimulated in vitro with the anti-CD3∈ mAb, 145–2C11, in either soluble (2C11s) or plate-bound (2C11i) form. In the young group, each mode of cell activation resulted in peak DNA synthesis at ∼48 h of culture; at this time point, the old group exhibited response levels to 2C11s or 2C11i that were ∼40% of those in the young group. However, in the presence of 2C11i, splenocytes from old donors showed a delayed peak response which approached the peak levels attained in the young group. To analyze the responsiveness of the CD4+ T cell subpopulation, this cell type was isolated from spleens of young or old mice and was stimulated in vitro with 2C11s or 2C11i, in the presence or absence of added accessory cells (T cell–depleted, irradiated splenocytes). The induction of DNA synthesis by 2C11s was accessory cell dependent, and the response in the old group were markedly reduced in comparison to those in the young group. In contrast, stimulation of DNA synthesis with 2C11i was relatively accessory cell independent, resulted in higher response levels in both age groups, and lessened the disparity between age groups. The analysis of IL-2 and IL-4 secretion by stimulated CD4+ cells revealed that, in response to 2C11s and accessory cells, only IL-2 accumulation was detectable and the levels in the young group were ∼10-fold higher than the IL-2 levels in the old group. However, stimulation of CD4+ cells with 2C11i and accessory cells yielded improved IL-2 production and a detectable IL-4 response in the old group, whereas the young group exhibited a response profile similar to that induced by 2C11s. Further analysis of the IL-2, IL-4, and IFNγ mRNA levels in 2C11i-stimulated CD4+ cells revealed that old donor cells accumulated similar levels of IL-2 transcripts, but higher levels of IL-4 and IFNγ transcripts, than young donor CD4+ cells. Finally, we analyzed splenic CD4+ cells for membrane expression of four molecules—3G11, 6C10, CD45RB, and CD44—thought to demarcate CD4+ cell subsets with restricted patterns of cytokine production. The CD4+ cell fraction of individual mice contained higher percentages of cell phenotypes associated with increased IL-4:IL-2 production ratios (i.e., 3G11lo, CD45RBlo) and with increased IFNγ synthesis (i.e., CD44hi). Taken together, these data show marked alterations in the CD4+ cell subset composition in old mice, detected at the levels of subset marker expression and profiles of cytokine production. Moreover, conclusions regarding CD4+ cell competency in old donors can differ depending on the choices of stimuli and readouts for cell function in the experimental design. Therefore, age-related differences in T cell reactivity in vitro may be partially explained by the shifts in the representation of individual CD4+ subsets, each with potentially unique activation requirements and functional attributes.
The size of the nave T-cell pool is governed by output from the thymus and not by replication. This pool contributes cells to the activated/memory T-cell pool whose size can be increased through cell multiplication; both pools together constitute the peripheral T-cell pool. Aging is associated with involution of the thymus leading to a reduction in its contribution to the nave T-cell pool; however, despite this diminished thymic output, there is no significant decline in the total number of T cells in the peripheral T-cell pool. There are, however, considerable shifts in the ratios of both pools of cells, with an increase in the number of activated/memory T cells and the accumulation in older individuals of cells that fail to respond to stimuli as efficiently as T cells from younger individuals. Aging is also associated with a greater susceptibility to some infections and some cancers. An understanding of the causal mechanism of thymic involution could lead to the design of a rational therapy to reverse the loss of thymic tissue, renew thymic function, increase thymic output, and potentially improve immune function in aged individuals.
The potential for vitamin E to modulate prostaglandin metabolism and alter immune response in aged mice was studied. Semi-purified diets containing 30 ppm or 500 ppm dl-α-tocopheryl acetate (VitE) were fed for 6 weeks to young (3 months) and old (24 months) C57BL/6J mice. Delayed hypersensitivity skin test to DNFB and the proliferative response of splenocytes to T- and B-cell mitogens were assessed. Ex-vivo synthesis of Prostaglandin E2 (PGE2) was measured in spleen homogenates and serum vitamin E was measured by HPLC. Vitamin E supplementation of aged mice enhanced percent ear swelling to DNFB as well as the mitogenic response of splenocytes to Con A and LPS (P < 0.05). Furthermore, spleen homogenates from old mice fed 30 ppm VitE had a significantly higher PGE2 level than young mice fed 30 ppm VitE and old mice fed 500 ppm VitE (3.20 ± 0.07 μg/g vs. 2.60 ± 0.08 and 2.3 ± 0.10, respectively). Thus, the vitamin E enhanced immune response of aged mice appears to be mediated by decreased prostaglandin synthesis.
The secondary antibody response to 5.0 microgram flagellin was studied by haemagglutination in 132 healthy or convalescent subjects given a primary challenge with 5.0 microgram flagellin from 1 to 44 months previously. The peak titre, expressed as total antibody, occurred at 2 weeks and was mainly immunoglobulin (Ig)G. The magnitude of the titre of total antibody was influenced predominantly by that of total antibody in the primary response (P less than 0.001), the interval between primary and secondary responses (P less than 0.005) and the subjects' age (P less than 0.05) and sex (P less than 0.08). Together these accounted for 23% of the variability observed in the secondary response, with total antibody titre in the primary response accounting for 11% of the variability. The titre of IgG antibody was likewise influenced by these four variables, but the influence of age or sex on IgG antibody was not statistically significant. In human vaccination programmes, choice of the appropriate interval between primary and booster inoculations could increase prophylactic effectiveness and, if two inoculations were to prove as effective as three, there would be reduced work and increased public acceptance. Moreover, the demonstrable capacity for responsiveness of aged and debilitated persons should encourage the wider use of appropriate prophylactic immunization in these groups.
Ageing is associated with impaired immune responses and increased infection-related morbidity. This study assessed the effect of physiological amounts of vitamins and trace elements on immunocompetence and occurrence of infection-related illness. 96 independently living, healthy elderly individuals were randomly assigned to receive nutrient supplementation or placebo. Nutrient status and immunological variables were assessed at baseline and at 12 months, and the frequency of illness due to infection was ascertained. Subjects in the supplement group had higher numbers of certain T-cell subsets and natural killer cells, enhanced proliferation response to mitogen, increased interleukin-2 production, and higher antibody response and natural killer cell activity. These subjects were less likely than those in the placebo group to have illness due to infections (mean [SD] 23 [5] vs 48 [7] days per year, p = 0.002). Supplementation with a modest physiological amount of micronutrients improves immunity and decreases the risk of infection in old age.
Numerous changes have been reported to occur in T cell responsiveness of mice with increasing age. However, most of these studies have examined polyclonal stimulation of spleen cells from a limited number of mouse strains. This study investigated the influence of genetic background, source of lymphocytes, and type of stimulus on age-associated changes in T cells response. Con A-induced proliferation and IL-2 and IFN-gamma production by splenic lymphocytes (SL) was significantly greater in CBA/Ca mice compared to C57BL/6 mice, regardless of age. SL of both strains exhibited the predicted age-dependent decline in proliferative response and an increase in IFN-gamma production in response to Con A. In contrast, however, only SL from C57BL/6 mice demonstrated the predicted age-dependent decline in Con A-induced IL-2 production; Con A-induced SL of young and aged CBA/Ca mice produced comparable amounts of IL-2. Differences in age-associated responses to Con A were also observed between SL and inguinal lymph node (ILN) cells of CBA/Ca mice. In contrast to SL, ILN cells demonstrated an increased proliferative response to Con A. However, lymphokine production by Con A-stimulated ILN cells from aged CBA/Ca mice was similar to that of Con A-stimulated SL from aged CBA/Ca mice. To determine if aged ILN T cells respond similarly to polyclonal and antigen-specific stimuli, keyhole limpet hemocyanin (KLH) responses of T cells isolated from ILN of aged and young CBA/Ca mice were examined. KLH-specific T cells from aged mice cultured with KLH-pulsed macrophages (M phi) from aged mice were significantly reduced in their ability to proliferate compared to KLH-specific T cells of young mice cultured with young KLH-pulsed M phi. In contrast to the expected results, the defect was not at the level of the T cells; proliferation of young T cells cultured with aged KLH-pulsed M phi was equivalent to the proliferation of aged T cells cultured with aged M phi. These results suggest that aging has differential effects on polyclonal and antigen-specific T cell proliferation and on polyclonal stimulation of T cells isolated from different lymphoid organs and from different strains of mice.
The demographic explosion of persons over 60 years of age is a reality in developed and developing countries alike. There is evidence that research on aging and nutrition in Third World countries is growing and developing. Specific research programs, and the linking of these programs in timely multicenter efforts, promise both valuable descriptive research for the benefit of national populations and comparative insights that will help us to learn more, collectively, about the intrinsic nature of the aging process itself.
The effect of age on the response of splenocytes to activation with anti-CD3 mAb and a combination of anti-CD3 mAb and TPA, as evidenced by interleukin-2 (IL-2) and interleukin-4 (IL-4) production and cell proliferation, was examined in the C57BL/6 and DBA/2 murine strains. Depending on the mode of activation, there were age and strain differences in IL-2 and IL-4 production. With all modes of activation, cells from the old C57BL/6 mice produced less IL-2 than their young counterparts. In DBA/2 mice there was no age-related difference in IL-2 production with anti-CD3 mAb activation alone, whereas when the same cell population was activated with anti-CD3 mAb and TPA an age-associated decrease in IL-2 production occurred. In both strains, there was an age-related increase in IL-4 production with anti-CD3 mAb activation. After addition of TPA, however, there was an age-related decrease in IL-4 production. An age-related decline in the proliferation occurred with all modes of activation in both mouse strains. There were also strain-related differences in proliferation after the addition of forskolin, an inhibitor of Th1-cell function. While forskolin inhibited the proliferation of cells from the young C57BL/6 mice only, in the DBA/2 mice proliferation of cells was inhibited in both age groups. There were no strain-related differences in inhibition by anti-transferrin receptor (TrfR) mAb, although cells from the old mice were slightly more sensitive to this inhibition.
While diarrheal disease is a well-recognized problem in children, its impact in the elderly has not been adequately assessed. Among the 4.06 million hospitalizations in 1985 in the McDonnell-Douglas Health Information System database, 98,185 hospitalizations, including 1,130 deaths, had gastroenteritis recorded as a discharge diagnosis. The authors analyzed the 87,181 hospitalizations and 514 deaths for which gastroenteritis was one of the top three diagnoses. Gastroenteritis was among the top three diagnoses in 9% of all hospitalizations of children 1-4 years of age, compared with 1.5% of hospitalizations throughout adulthood (greater than or equal to 20 years). Only 0.05% of hospitalizations involving gastroenteritis were fatal for children younger than 5 years, compared with 3% in individuals 80 years or older. While children aged less than 5 years and adults aged 60 years or more each comprised one-fourth of hospitalizations involving gastroenteritis, the older group represented 85% of diarrheal deaths. Age was the most important risk factor for death subsequent to a hospitalization involving gastroenteritis (odds ratio = 52.6, 95% confidence interval 37.0-76.9 for age greater than or equal to 70 years vs. less than 5 years). Gastroenteritis is a large, underemphasized public health problem among the elderly, among whom its case-fatality ratio is higher than in children.
Thirty elderly long-stay patients were randomly allocated to receive either placebo or dietary supplementation with vitamins
A, C and E for 28 days. Nutritional status and cell-mediated immune function were assessed before and after the period of
supplementation.
Following vitamin supplementation, cell-mediated immune function improved as indicated by a significant increase in the absolute
number of T cells (p<0.05), T4 subsets (p<0.05), T4 to T8 ratio (p<0.01) and the proliferation of lymphocytes in response
to phytohaemagglutinin (p<0.01). In contrast, no significant changes were noted in the immune function of the placebo group.
We conclude that supplementation with the dietary antioxidants vitamins A, C and E can improve aspects of cell-mediated immune
function in elderly long-stay patients.
The nutritional problems of developing countries are conditioned by poverty, near exclusive reliance on plant sources of nutrients, and high rates of infections. Common deficiency diseases include protein-energy malnutrition, nutritional anemias, vitamin A deficiency, iodine deficiency, and possibly others. Population subgroups at particularly high risk are the children and women of poor families. Control of these nutritional diseases requires systematic diagnosis of the existing situation and appropriate intervention strategies such as targeted food and specific micronutrient supplementation, food fortification, nutrition education, and reductions in infections as well as general improvements in economic conditions and social equity.
--Diarrhea is an important cause of death among young children in both developing and developed countries, but little is known about diarrheal death among adults. In this study, we examined trends in diarrheal deaths among all age groups in the United States.
--We reviewed national mortality data complied by the National Center for Health Statistics, Hyattsville, Md, which consists of information from all death certificates filed in the United States for the period 1979 through 1987. A death for which diarrhea was listed as an immediate or underlying cause was considered a "diarrheal death" and included in the analysis.
--We found that 28,538 persons died of diarrhea cited as either an immediate or the underlying cause of death during the 9-year period. A majority of diarrheal deaths occurred among the elderly (older than 74 years of age, 51%), followed by adults 55 to 74 years of age (27%), and young children (younger than 5 years of age, 11%). For the elderly, adjusted risk factors for dying of diarrhea included being white, female, and residing in a long-term care facility. Only the elderly and young children had clear, distinct winter peaks of diarrheal deaths, suggesting that the diarrhea may, in part, be infectious in origin.
--For the elderly, more directed studies of those at risk, such as nursing home residents, are needed to determine if oral rehydration therapy, vaccines, or other preventive measures might benefit this population.
This paper addresses itself to the problems faced by the aged with regards to the use and availability of health services in Sub-Saharan Africa (SSA). The paper maintained that the development of a sound public policy on ageing in SSA requires two types of knowledge; an understanding of what consequences will follow from a particular course of action, and an evaluation of the desirability of those consequences. It concluded that there is a need to improve the database that will form a basis for any policy prescription that is geared towards alleviating the problems of the aged in this sub-region.
Clinical experience suggests the delayed-type hypersensitivity (DTH) skin test lacks sensitivity in assessing the integrity of systemic cell-mediated immunity (CMI) or the status of recent or remote mycobacterial infections in elderly nursing home residents. In an attempt to clarify this issue, DTH reaction to purified protein derivative (PPD), tetanus toxoid and Candida albicans was compared with circulating thymus-derived lymphocyte (T cell) proliferation (TCP) to stimulation with PPD and anti-CD3 antibody in 24 randomly selected nursing home residents. The DTH reaction and the TCP response correlated reasonably well among the DTH reactors but poorly among DTH nonreactors, suggesting there may be age-related immunologic changes in the skin itself. Also, the DTH skin test to PPD alone was found to be a poor index of the integrity of systemic CMI.
The objective of this study was to determine the effects of a year of Zn supplementation on Zn concentrations in circulating cells and on cellular immune functions in the elderly. Subjects, aged 60-89, were given a placebo, 15 mg Zn, or 100 mg Zn daily for 12 months. All subjects also received a multivitamin/mineral supplement that contained no additional Zn. Blood samples were drawn and immune functions assessed prior to and at 3, 6, 12, and 16 months after beginning Zn supplementation. Subject diets were also assessed at each visit. Dietary folate, pyridoxine, alpha-tocopherol, copper, zinc, and magnesium were consistently below recommended intakes. Although plasma Zn increased significantly in the 100 mg Zn treatment group, concentrations of Zn in erythrocytes, mononuclear cells, polymorphonuclear leukocytes, and platelets were not significantly increased by zinc supplementation. Natural killer cell activity was transiently enhanced by the 100 mg/day dose of Zn. There was a progressive improvement in delayed dermal hypersensitivity (DDH) and in lymphocyte proliferative responses to two mitogens; this may have been due to one or more components of the multivitamin/mineral supplement administered to all study subjects. The enhancement of DDH was significantly greater in the placebo group than in either zinc treatment group. Thus, zinc had a beneficial effect on one measure of cellular immune function while simultaneously having an adverse effect on another measure of cellular immunity.
The present study was conducted in an attempt to explore a possible mechanism for zinc-deficiency-induced T-lymphocyte dysfunction in the elderly. Eight elderly subjects aged 65-78 years served in this study. All subjects were anergic, zinc-deficient and had low activity of erythrocyte nucleoside phosphorylase. Baseline values for zinc status and immunological indices were established after which subject were treated with zinc acetate (60 mg elemental zinc per day given orally) for a period of 4 1/2 months. Zinc supplementation resulted in a significant increase in the concentrations of zinc in plasma (P less than 0.001), erythrocytes (P less than 0.05), lymphocytes (P less than 0.001) and neutrophils (P less than 0.005). The activity of nucleoside phosphorylase in erythrocytes increased significantly (P less than 0.001) as a result of zinc treatment. This was associated with significant improvement in the delayed cutaneous hypersensitivity reactions.
Cutaneous-delayed hypersensitivity was studied by one and two-step Mantoux-type skin tests to four standard antigens in 33 elderly nursing home residents, 34 geriatric clinic patients, and 20 healthy young adult controls. Demographic and anthropometric data were collected to determine the effects of nutrition and other variables on cutaneous-delayed hypersensitivity. Anergy (a lack of response greater than 5 mm of induration when read at 48 hours) to any of the four antigens occurred in 34% of nursing home residents, 17% of geriatric clinic patients, and none of the healthy young adults. Mean and maximal responses were less in the nursing home residents than the clinic patients or controls, even if anergic individuals were excluded from analysis, suggesting both a qualitative and quantitative decline in cell-mediated immune function in this elderly population. Repeat testing with each antigen for which there was a negative initial response revealed a "booster" affect of 7 to 19% and occurred as commonly in the healthy young adults as in the nursing home residents or geriatric clinic patients. The mumps antigen elicited strong responses in the healthy young adults, but weak reactions in the nursing home residents. An unexpectedly high prevalence of positive tuberculin (PPD) responses occurred in the nursing home residents, suggesting recent exposure. Analysis of anthropometric and demographic characteristics show that neither nutritional status nor age alone can account for differences in cutaneous-delayed hypersensitivity observed between populations. Cutaneous-delayed hypersensitivity may vary widely between elderly populations and have important practical implications for the tuberculin test.
In aged as compared with young people T-cell immune responses tested by three different systems were significantly depressed; in the aged (more than sixty years) compared with the young (less than twenty-five) the number of positive delayed-type hypersensitivity reactions to five ubiquitous antigens was significantly lower; the lymphocyte response to the mitogen phyto-hæmagglutinin was significantly lower; and the presumed T-cell-dependent late IgG response to 5 μg. of monomeric flagellin was significantly lower. Furthermore, the mortality of very old people (over eighty), who were hyporesponsive in tests for delayed hypersensitivity, was significantly greater over a two-year period than that of comparable people who were not hyporesponsive.
The relation of diet and host resistance was mentioned in the ancient Puranic scriptures in India. In the past 50 years, the observation that the thymus is involuted in people dying of starvation activated the study of nutritional immunology and the publication of two reports on immunocompetence in protein-energy malnutrition (PEM) in India and South Africa gave the topic impetus. The examination of nutrition-immunity-interactions has provided valuable insights into not only the determinants of infection but also immunoregulation in general. Available data are reviewed.
Zinc is known to have beneficial effects on the immune response. In an attempt to modify age-associated immune dysfunction, supplemental zinc was administered to 15 subjects over 70 years of age (220 mg zinc sulfate twice daily for a month). As compared to 15 controls, matched for age and sex, there was a significant improvement in the following immune parameters in the treated group: (1) number of circulating T lymphocytes; (2) delayed cutaneous hypersensitivity reactions to purified protein derivative, Candidin and streptokinase-streptodornase; (3) immunoglobulin G (IgG) antibody response to tetanus vaccine. Zinc treatment had no influence on the number of total circulating leukocytes or lymphocytes, or on the in vitro lymphocyte response to three mitogens: phytohemagglutinin (PHA), concanavalin A (Con A) and pokeweed mitogen (PWM). The data suggest that the addition of zinc to the diet of old persons could be an effective and simple way to improve their immune function.
Thymic tissue obtained at autopsy from 123 victims of sudden death, ranging from neonates to individuals older than 80 years and predominantly male, was studied with histometric techniques, i.e. a combination of test point analysis and planimetry on unit optical fields. The pattern of 'natural' age-dependent involution of the thymic cortex was examined using computerized mathematical models. The range of variations of results was greatest in children and young adults, followed by the very old, then the middle age group. In a first approximation, regression for thymic cortical volume in individuals older than 15 years corresponded better to a negative exponential than to a negative linear function of age. Best fits for the data suggest at least a two-component negative exponential function of age, with a steeper slope of the regression for individuals beyond the age of 30 years. Extrapolation on a log-normal plot of regression lines for thymic cortical involution points to near-zero values at an age range below the estimated maximum human life span, corresponding to the steepest slope of survival curves in Western Europe.
Aging is associated with a progressive decline in the immune system and a greater susceptibility to infection. This double-blind, placebo-controlled study, examined the effect of a vitamin and trace element supplement on immune responses of healthy, noninstitutionalized elderly subjects. Forty-seven subjects aged 61-79 years were randomly assigned to receive placebo or micronutrient supplementation for one year. Thirty-five individuals completed the one-year study. Immune function was assessed before and after the period of supplementation. Cell-mediated immune function assessed by the number of T cells and subsets remained constant in the supplemented group and there was a significant increase in CD57 natural killer cells. In contrast, a significant decrease in T cells, CD4 cells, and CD4: CD8 ratio was noted in the placebo group. Supplementation with micronutrients can play a crucial role in the maintenance of normal immune function in the elderly.
