TrendImmunosenescence☆
Abstract
The deterioration of the immune system in ageing — ‘immunosenescence’ — is thought to contribute to increased morbidity and mortality from infections, and possibly autoimmune disease and cancer, in the elderly. A recent meeting★ discussed the molecular basis of this process.
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When GETomics meets aging and exercise in COPD: GETomics, exercise, ageing and COPD
2023, Respiratory MedicineThe term GETomics has been recently proposed to illustrate that human health and disease are actually the final outcome of many dynamic, interacting and cumulative gene (G) – environment (E) interactions that occur through the lifetime (T) of the individual. According to this new paradigm, the final outcome of any GxE interactions depends on both the age of the individual at which such GxE interaction occurs as well as on the previous, cumulative history of previous GxE interactions through the induction of epigenetic changes and immune memory (both lasting overtime).
Following this conceptual approach, our understanding of the pathogenesis of chronic obstructive pulmonary disease (COPD) has changed dramatically. Traditionally believed to be a self-inflicted disease induced by tobacco smoking occurring in older men and characterized by an accelerated decline of lung function with age, now we understand that there are many other risk factors associated with COPD, that it occurs also in females and young individuals, that there are different lung function trajectories through life, and that COPD is not always characterized by accelerated lung function decline.
In this paper we discuss how a GETomics approach to COPD may open new perspectives to better understand its relationship with exercise limitation and the ageing process.
The Interplay Between the Immune System, Tumor Suppressor Genes, and Immune Senescence in Mesothelioma Development and Response to Immunotherapy
2023, Journal of Thoracic OncologyDespite efforts to ban asbestos mining and manufacturing, mesothelioma deaths in the United States have remained stable at approximately 2500 cases annually. This trend is not unique to the United States but is also a global phenomenon, associated with increased aging of populations worldwide. Although geoeconomic factors such as lack of regulations and continued asbestos manufacturing in resource-poor countries play a role, it is essential to consider biological factors such as immune senescence and increased genetic instability associated with aging. Recognizing that mesothelioma shares genetic instability and immune system effects with other age-related cancers is crucial because the impact of aging on mesothelioma is frequently assessed in the context of disease latency after asbestos exposure. Nevertheless, the long latency period, often cited as a reason for mesothelioma’s elderly predominance, should not overshadow the shared mechanisms. This communication focuses on the role of immune surveillance in mesothelioma, particularly exploring the impact of immune escape resulting from altered TSG function during aging, contributing to the phylogenetic development of gene mutations and mesothelioma oncogenesis. The interplay between the immune system, TSGs, and aging not only shapes the immune landscape in mesothelioma but also contributes to the development of heterogeneous tumor microenvironments, significantly influencing responses to immunotherapy approaches and survival rates. By understanding the complex interplay between aging, TSG decline, and immune senescence, health care professionals can pave the way for more effective and personalized immunotherapies, ultimately offering hope for better outcomes in the fight against mesothelioma.
Socioeconomic and race/ethnic differences in immunosenescence: Evidence from the Health and Retirement Study
2023, Brain, Behavior, and ImmunityThe COVID-19 pandemic has highlighted the urgent need to understand variation in immunosenescence at the population-level. Thus far, population patterns of immunosenescence have not well described.
We characterized measures of immunosenescence from the 2016 Venous Blood Study from the nationally representative U.S Health and Retirement Study (HRS) of individuals ages 50 years and older.
Median values of the CD8+:CD4+, EMRA:Naïve CD4+ and EMRA:Naïve CD8+ ratios were higher among older participants and were lower in those with additional educational attainment. Generally, minoritized race and ethnic groups had immune markers suggestive of a more aged immune profile: Hispanics had a CD8+:CD4+ median value of 0.37 (95 % CI: 0.35, 0.39) compared to 0.30 in non-Hispanic Whites (95 % CI: 0.29, 0.31). Non-Hispanic Blacks had the highest median value of the EMRA:Naïve CD4+ ratio (0.08; 95 % CI: 0.07, 0.09) compared to non-Hispanic Whites (0.03; 95 % CI: 0.028, 0.033). In regression analyses, race/ethnicity and education were associated with large differences in the immune ratio measures after adjustment for age and sex.
Lower educational attainment and minoritized racial ethnic status were associated with higher levels of immunosenescence. This population variation may have important implications for both risk of age-related disease and vulnerability to emerging pathogens (e.g., SARS-CoV-2).
The role of curcumin in aging and senescence: Molecular mechanisms
2021, Biomedicine and PharmacotherapyHealthy aging and human longevity are intricate phenotypes affected by environmental factors such as physical exercise, diet, health habits, and psychosocial situations as well as genetic factors. Diet and caloric restriction have a crucial role in healthy aging. Curcumin, a polyphenolic compound isolated from the Curcuma longa, has been shown to exert anti-aging characteristics. Recently, investigations on curcumin with regard to aging and age-associated disease in model organisms has described that curcumin and its metabolites, prolong the mean lifespan of some aging model organisms such as C. elegans, D. melanogaster, yeast, and mouse. It has been proposed to have several biological activities, such as antioxidative, anti-inflammatory, anticancer, chemopreventive, and anti-neurodegenerative characteristics. In several studies on various model organisms it has been shown that the lifespan extension via curcumin treatment was connected with enhanced superoxide dismutase (SOD) activity, and also declined malondialdehyde (MDA) and lipofuscin levels. As well as the pivotal role of curcumin on the modulating of major signaling pathways that influence longevity of organisms like IIS, mTOR, PKA, and FOXO signaling pathways. This review defines the use of curcumin in traditional and modern medicine, its biochemistry and biological functions, such as curcumin's anti-aging, anti-cancer, anti-microbial, anti-inflammatory, and anti-oxidant characteristics. Also, the review further describes the role of curcumin in a pharmacological context and new insights on its therapeutic capacity and restrictions. Particularly, the review emphasizes in-depth on the efficiency of curcumin and its mechanism of action as an anti-aging compound and also treating age-related disease.
Moderate levels of physical fitness maintain telomere length in non-senescent T CD8+ cells of aged men
2020, ClinicsImmunosenescence is an age-associated change characterized by a decreased immune response. Although physical activity has been described as fundamental for maintaining the quality of life, few studies have evaluated the effects of different levels of exercise on telomere length in aged populations. The present study aimed to analyze the effects of different levels of physical activity, classified by the Maximal oxygen consumption (VO2 max) values, on the telomere length of memory Cluster of differentiation (CD) CD4+(CD45ROneg and CD45RO+), effector CD8+CD28neg, and CD8+CD28+ T cells in aged individuals.
Fifty-three healthy elderly men (aged 65-85 years) were included in this study. Their fitness level was classified according to the American College of Sports Medicine (ACSM) for VO2 max (mL/kg/min). Blood samples were obtained from all participants to analyze the percentage of CD3, CD4, CD8, CD28+, naïve, and subpopulations of memory T cells by using flow cytometry. Furthermore, using the Flow-FISH methodology, the CD4+CD45RO+, CD4+CD45ROneg, CD8+CD28+, and CD8+CD28negT cell telomere lengths were measured.
There was a greater proportion of effector memory T CD4+ cells and longer telomeres in CD8+CD28+ T cells in the moderate physical fitness group than in the other groups. There was a higher proportion of terminally differentiated memory effector T cells in the low physical fitness group.
A moderate physical activity may positively influence the telomere shortening of CD28+CD8+T cells. However, additional studies are necessary to evaluate the importance of this finding with regard to immune function responses in older men.
Specificity of the management of metastatic renal cancer in the older patient
2019, Progres en UrologieDéfinir les aménagements du traitement médical par les anti-angiogéniques, l’inhibiteur de mTOR ou les immunothérapies systémiques lors de la prise en charge du cancer du rein métastatique chez les patients âgés.
Recherche bibliographique à partir de la base de données bibliographiques Medline (NLM outil Pubmed) et Embase à partir des mots-clés suivants : cancer du rein métastatique, personne âgé, traitement.
Les critères de sélections du traitement médical du cancer du rein métastatique chez les patients âgés sont le score IMDC nécessairement complété par le performance status, le profil de tolérance du traitement, les interactions médicamenteuses plus fréquentes, l’observance du traitement, la capacité de gestion de ses effets secondaires et la préférence des patients. Chacun de ces critères est détaillé de manière critique.
L’efficacité et la tolérance de traitements médicaux du cancer du rein métastatique n’ont pas été rapportées comme différentes en fonction de l’âge. Aucune adaptation posologique n’est recommandée de principe. Toutefois, la prévention et le traitement précoce des effets secondaires des traitements doivent être renforcés chez les patients âgés.
To define the necessary arrangements of medical treatment with anti-angiogenics, mTOR inhibitor or systemic immunotherapies in the management of metastatic renal cell carcinoma in elderly patients.
Bibliographical search was performed from the Medline bibliographic database (NLM Pubmed tool) and Embase focused on: metastatic renal cell carcinoma, elderly, treatment.
The selection criteria for the medical treatment of metastatic renal cell carcinoma in elderly patients are the IMDC score, necessarily complemented by performance status, the tolerability profile of treatments, more frequent drug interactions, treatment adherence, management capacity of side effects, and patient preference. Each of these criteria is detailed in critical ways.
The efficacy and tolerability of medical treatments for metastatic renal cancer have not been reported as different depending on age. No dosage adjustment is recommended in principle. However, prevention and early treatment of side effects of treatment should be strengthened in elderly patients.
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EUCAMBIS is supported by the European Union Biomedical and Health Research Programme Biomed 1 (contract CT94-1209). This report has been composed on behalf of all EUCAMBIS members (E. Mariani, Y. Barnett, C. Bartoloni, G. ligthart, C. Paraskeva, E. Remarque, S. Shall, V. Sorrentino, G.M. Taylor and the two authors).
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The 5th EUCAMBIS Congress on the Molecular Biology of Immunosenescence was held at Córdoba, Spain, on 14–18 May 1997.