Objective Age-related increment of the prevalence of CD4^＋CD25^＋ regulatory T （Treg） cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The a...Objective Age-related increment of the prevalence of CD4^＋CD25^＋ regulatory T （Treg） cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8＋ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^＋CD25^＋ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease （AD） and Parkinson disease （PD）. The impaired condition of CD4＋ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.展开更多
Objective： Aging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system. The medicinal properties of Morinda citrifolia L. have been widely ex...Objective： Aging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system. The medicinal properties of Morinda citrifolia L. have been widely exploited for the treatment of age-associated diseases. This study aims to investigate the in vitro and in vivo effects of noni（M. citrifolia） fruit juice（NFJ） on neuro-immunomodulation in the lymph node lymphocytes of F344 rats.Methods： Lymphocytes isolated from axillary and inguinal lymph nodes of young（3–4 months） and old（18–21 months） rats were treated in vitro with different concentrations（0.0001%, 0.01%, and 1%） of NFJ for a period of 24 h. In the in vivo study, old（16–17 months） male F344 rats were treated with 5 mL/kg body weight of 5%, 10% and 20% of NFJ, twice a day, by oral gavage, and lymph node lymphocytes were isolated after 60 d. Concanavalin A（Con A）-induced lymphocyte proliferation, interleukin-2（IL-2）and interferon-γ（IFN-γ） production and expression of intracellular markers, such as phosphoextracellular signal-regulated kinase（p-ERK1/2）, phospho-γ AMP response element-binding protein,phospho-protein kinase B（p-Akt）, phospho-tyrosine hydroxylase（p-TH）, phospho-nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α（p-IκB-α） and phospho-nuclear factor-κB（p-NF-κB p65 and p50） were examined in the lymphocytes of lymph nodes.Results： NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50.Conclusion： These results suggest that the immunostimulatory properties of NFJ are facilitated through intracellular signaling pathways involving ERK1/2, Akt and NF-κB.展开更多
Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy ...Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus(HIV) disease progression, and functional T-cell responses in HIV-tuberculosis(HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB coinfection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.展开更多
Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the b...Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.展开更多
Immunosenescence refers to the abnormal activation or dysfunction of the immune system as people age.Inflammaging is a typical pathological inflammatory state associated with immunosenescence and is characterized by e...Immunosenescence refers to the abnormal activation or dysfunction of the immune system as people age.Inflammaging is a typical pathological inflammatory state associated with immunosenescence and is characterized by excessive expression of proinflammatory cytokines in aged immune cells.Chronic inflammation contributes to a variety of age-related diseases,such as neurodegenerative disease,cancer,infectious disease,and autoimmune diseases.Although not fully understood,recent studies contribute greatly to uncovering the underlying mechanisms of immunosenescence at the molecular and cellular levels.Immunosenescence is associated with dysregulated signaling pathways(e.g.,overactivation of the NF-κB signaling pathway and downregulation of the melatonin signaling pathway)and abnormal immune cell responses with functional alterations and phenotypic shifts.These advances remarkably promote the development of countermeasures against immunosenescence for the treatment of age-related diseases.Some anti-immunosenescence treatments have already shown promising results in clinical trials.In this review,we discuss the molecular and cellular mechanisms of immunosenescence and summarize the critical role of immunosenescence in the pathogenesis of age-related diseases.Potential interventions to mitigate immunosenescence,including reshaping immune organs,targeting different immune cells or signaling pathways,and nutritional and lifestyle interventions,are summarized.Some treatment strategies have already launched into clinical trials.This study aims to provide a systematic and comprehensive introduction to the basic and clinical research progress of immunosenescence,thus accelerating research on immunosenescence in related diseases and promoting the development of targeted therapy.展开更多
With the aging of the global population,older people living with HIV(OPLWH)have emerged as a focal point in HIV/AIDS research.Although antiretroviral therapy has demonstrated positive effects in OPLWH,concerns persist...With the aging of the global population,older people living with HIV(OPLWH)have emerged as a focal point in HIV/AIDS research.Although antiretroviral therapy has demonstrated positive effects in OPLWH,concerns persist regarding overall poor immune reconstitution and elevated rates of age-related comorbidities,such as cardiovascular disease,bone disease,and cognitive impairment.This review aims to elucidate the mechanisms underlying immunosenescence and the interaction of immunosenescence with HIV infection,further exploring its role in the pathogenesis of HIV infection during aging.Aging-induced involution of the immune system,along with chronic inflammation and infection,can induce immunosenescence,leading to immune dysfunction that impairs the effective control of HIV infection.In addition,HIV infection induces immunosenescence through persistent inflammation and immune activation,even under treatment.The combined effects of aging and HIV infection accelerate the progression of immunosenescence in OPLWH,increasing their susceptibility to multiple age-related diseases.The unfavorable prognosis observed among OPLWH is largely attributed to increased levels of immunosenescence.A comprehensive understanding of the relationship between immunosenescence and HIV infection is crucial for developing targeted therapeutic strategies for this vulnerable population.展开更多
Immunosenescence represents a natural process of immune degeneration that occurs with aging.Although this process is a common phenomenon in elderly patients,it extremely gets involved in tumor development and affects ...Immunosenescence represents a natural process of immune degeneration that occurs with aging.Although this process is a common phenomenon in elderly patients,it extremely gets involved in tumor development and affects the clinical efficacy of cancer immunotherapy.Emerging studies demonstrate that improving immunosenescence may greatly enhance the efficacy and prognosis of cancer immunotherapy in elderly patients.However,limited clinical and preclinical studies have addressed immunosenescence as a therapeutic consideration,and the challenges of traditional cancer immunotherapy remain to be resolved.Nanomedicine,integrating nanotechnology and medicine,employs advanced nanomaterials and targeted drug delivery systems to achieve optimal region-specific biodistribution and therapeutic efficacy.This review systematically describes the various elements of immunosenescence and the impact on the vicious cycle between them and the tumor microenvironment.Meanwhile,based on a comprehensive understanding of the importance of immunosenescence in cancer formation and progression among elderly populations and the advantages of nanomedicine,we detail the feasibility of nanomedicine in improving immunosenescence to enhance cancer immunotherapy.Furthermore,this review also systematically discusses the synergistic mechanisms and clinical application prospects of nanomaterials with novel immunotherapy technologies,while also providing insights into the challenges and future directions in this field.In conclusion,this review provides comprehensive insights into the design and development of nanodrugs for improving immunosenescence,aiming to assist scientists who wish to expand their research scope and engage in this interdisciplinary field.展开更多
Immunosenescence is described as a decline in the normal functioning of the immune system associated with physiologic ageing.Immunosenescence contributes to reduced efficacy to vaccination and increased susceptibility...Immunosenescence is described as a decline in the normal functioning of the immune system associated with physiologic ageing.Immunosenescence contributes to reduced efficacy to vaccination and increased susceptibility to infectious diseases in the elderly.Extensive studies of laboratory animal models of ageing or donor lymphocyte analysis have identified changes in immunity caused by the ageing process.Most of these studies have identified phenotypic and functional changes in innate and adaptive immunity.However,it is unclear which of these defects are critical for impaired immune defense against infection.This review describes the changes that occur in innate and adaptive immunity with ageing and some age-related viral diseases where defects in a key component of immunity contribute to the high mortality rate in mouse models of ageing.展开更多
Immune checkpoint inhibitors(ICIs)are employed in immunotherapeutic applications for patients with weakened immune systems and can improve the ability of T cells to kill cancer cells.Although ICIs can potentially trea...Immune checkpoint inhibitors(ICIs)are employed in immunotherapeutic applications for patients with weakened immune systems and can improve the ability of T cells to kill cancer cells.Although ICIs can potentially treat different types of cancers in various groups of patients,their effectiveness may differ among older individuals.The reason ICIs are less effective in older adults is not yet clearly understood,but age-related changes in the immune system,such as immunosenescence and inflammation,may play a role.Therefore,this review focuses on recent advances in understanding the effects of immunosenescence and inflammation on the efficacy of ICIs.展开更多
Myeloid-derived suppressor cells(MDSCs)are a group of heterogeneous immature cells with a strong immunosuppressive function in myeloid cells,which are impeded in the differentiation of myeloid cells under the patholog...Myeloid-derived suppressor cells(MDSCs)are a group of heterogeneous immature cells with a strong immunosuppressive function in myeloid cells,which are impeded in the differentiation of myeloid cells under the pathological conditions of hypoxia,inflammation,infection,and cancer.As individuals age,there is a significant increase in myeloid-derived suppressor cells(MDSCs),which subsequently enhance the immunosuppressive functions of Tregs(regulatory T cells)and Bregs(regulatory B cells).Therefore,MDSC may be related to immune system remodeling,thereby preventing excessive lesions caused by aging.This indicates that MDSC could serve as a potent inducer of immune senescence.Immune senescence,characterized by immune dysfunction with aging,is closely linked to the onset of diseases like infections,pulmonary fibrosis,and tumors.To achieve the purpose of anti-aging by intervening in immune aging and slow down the occurrence and development of related diseases.Therefore,understanding the biological characteristics of MDSC and its role in immune aging is crucial for immunotherapy targeting MDSC.This article reviews the different roles of MDSC in immune aging and its relationship with pulmonary fibrosis,tumor and other related diseases to provide theoretical basis for more comprehensive targeted MDSC immunotherapy.展开更多
Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the ...Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the whole bone marrow adherence method and characterized.A rat model of aging was produced by daily subcutaneous injection of D-galactose into the back of the neck.Rat spleen lymphocyte isolate kit to isolate spleen lymphocytes from aging rats and young rats.In vitro,the co-culture system of BMSCs and aging rats lymphocytes was established,and under the induction of mitogen LPS and ConA,the proliferative activity of lymphocytes in each group was detected by CCK-8 assay,the levels of IgM and IgG in the culture supernatant of each group was detected by ELISA,and the IL-2 radioimmunoassay kits were used to detect the content of IL-2 in the supernatant of each group.Results:(1)The isolated adherent cells showed the characteristics of BMSCs,including spindle-shaped morphology,high expression of CD29,CD44,low expression of CD34 and CD45,and osteogenic/adipogenic ability.(2)Under LPS induction,lymphocyte proliferative activity and secretion of immunoglobulin IgG were reduced in the aging group compared with the young group,and co-culture with BMSCs reversed this trend.(3)Under ConA induction,the IL-2 content of BMSCs co-cultured with aging lymphocytes was higher than that of aging lymphocytes alone(P<0.0001);the IL-2 content of CsA co-cultured with aging lymphocytes was lower than that of aging lymphocytes alone(P<0.0001).Conclusion:BMSCs have immunomodulatory effects on the spleen lymphocytes of aging rats in vitro.展开更多
Given the protective roles of 25-hydroxyvitamin D (25(OH)D or vitamin D) in musculoskeletal health and the potential beneficial effects of vitamin D supplementation in reducing the risk of various chronic diseases, in...Given the protective roles of 25-hydroxyvitamin D (25(OH)D or vitamin D) in musculoskeletal health and the potential beneficial effects of vitamin D supplementation in reducing the risk of various chronic diseases, intensive repletion of vitamin D has been widely advocated. Of note, CD8 T cells have the highest levels of the vitamin D receptor compared with other major immune cells. The effects of vitamin D on CD8 T cells during aging, however, remain unclear. This study determined the relationship between vitamin D levels and CD8 T cell status in 34 healthy female subjects (all >60 years old). The CD8 T-cell phenotype was defined by the surface expression of CD28 and CD95. The low-25(OH)D serum groups (≤30 ng/ml) had higher percentages of CD28+CD95–CD8+ (na?ve) T cells and lower percentages of CD28+CD95+CD8+ (effector) T cells. By contrast, subjects with high levels of 25(OH)D had very low percentages of na?ve CD8 T cells but very high percentages of effector CD8 T cells. There was a significant inverse correlation between 25(OH)D levels and the frequency of na?ve CD8 T cells. The results show that higher levels of vitamin D are correlated with decreased frequencies of na?ve CD8 T cells during early aging, suggesting that higher levels of 25(OH)D accelerate CD8 T cell senescence. These results warrant further evaluation of the effects of vitamin D supplementation in immune aging.展开更多
Geriatric care during coronavirus disease 2019 is a real concern for all countries whether it is developed or developing.Poor tolerability for conventional medicines,co-morbidities,weak immune system,high oxidative st...Geriatric care during coronavirus disease 2019 is a real concern for all countries whether it is developed or developing.Poor tolerability for conventional medicines,co-morbidities,weak immune system,high oxidative stress,arterial aging,psychological stress and somatization are few possible reasons for high vulnerability of elderly people for coronavirus disease 2019.Beside high vulnerability of elderly people other major lacunas like improper nurturing,health care services,delayed in providing emergency treatment facilities are also major concern.Therefore it is require to make them self dependent and self sufficient in taking care for themselves by providing information of simple household remedies and simple life style measures that can be adopted easily,tolerable,accessible,affordable and above all safe to use.The article discusses simple spices that can be use as medicines for the management of coronavirus disease 2019 related diseases along with depiction of simple yogic techniques that can be performed indoor to maintain physical activity.展开更多
Ageing is associated with several anatomical and physiological changes of the organism, and the increase in global elderly population promotes the research to develop strategies to improve their quality of life. In th...Ageing is associated with several anatomical and physiological changes of the organism, and the increase in global elderly population promotes the research to develop strategies to improve their quality of life. In this work, we characterized the immunological alterations naturally produced during aging in a mice model, and evaluated the effect of probiotic Lactobacillus (L.) rhamnosus CRL1505 administration on those immunological parameters. We demonstrated that L. rhamosus CRL1505 was able to improve peritoneal macrophages phagocytic activity, and the number of intestinal IgA<sup>+</sup> cells in aged mice, reaching values of those parameters similar to young adult mice. The results of this work indicate that is plausible that the immunobiotic CRL1505 strain may find applications as a beneficial immunomodulator in aging to reinforce the intestinal and systemic immunity. The immune modulation in aging induced by L. rhamnosus CRL1505 could lead to the development of new strategies for functional foods specifically tailored for the elderly.展开更多
The aging microenvironment,as a key driver of tumorigenesis and progression,plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype(SASP).SASP co...The aging microenvironment,as a key driver of tumorigenesis and progression,plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype(SASP).SASP consists of a variety of interleukins,chemokines,proteases,and growth factors.It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms,thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment.Furthermore,these secreted factors activate key signaling pathways such as NF-κB,cGAS-STING,and mTOR,which regulate the expression of immune-related molecules(such as PDL1)and promote the recruitment of immunosuppressive cells,including regulatory T cells and myeloid-derived suppressor cells.This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment.Furthermore,the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms,including approaches to inhibit SASP secretion or eliminate senescent cells.Although these strategies have shown promise in certain tumor models,the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies.This highlights the need for further research into adaptive stratification and personalized treatment approaches.Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.展开更多
This study was performed to build region-specific reference ranges of peripheral blood lymphocyte subsets for Chinese healthy adults from the young to the elderly and analyze the trends of changes in lymphocyte subset...This study was performed to build region-specific reference ranges of peripheral blood lymphocyte subsets for Chinese healthy adults from the young to the elderly and analyze the trends of changes in lymphocyte subsets for evaluating the impact of age on the values.151 healthy adults aged 19-86 were recruited based on the SENIEUR protocol.Three sets of reference ranges were finally built applicable for the healthy young(19-44 years),middle-aged(45-64 years) and elder adults(≥65).Comparisons in parameters among the three cohorts showed that a statistically significant increase in CD16CD56+ NK cell was observed between the middle-aged and elder cohorts,whereas for the majority of the parameters,a significant decline was observed between the young and the middle-aged cohorts.Further results showed that inverse correlations were observed between the age and CD19+ B,CD3+ T,CD3+CD4+ T,CD4+CD45RA+CD62L+ nave T cell and CD4+CD28+/CD4+,while the positive one was identified between the age and the NK cell.These significant changes of the most of immune parameters provided evidence for immunosenescence.Notably,T cell activation markers of CD8+CD38+ and CD8+HLA-DR+ showed reverse trends of association with age,which provides a clue for further researches on the mechanisms underlying the paradoxical clinical presentation of the elder patients.展开更多
Background Immunosuppressive regulatory T cells （Tregs） participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change lea...Background Immunosuppressive regulatory T cells （Tregs） participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 （FoxP3） in the aging process and its relationship with lung tumors in humans and mice. Methods The percentage of CD4＋CD25＋CD127lowTregs and expression of FoxP3 mRNA were analyzed using flow cytometry （FCM） and real-time fluorescence-based quantitative polymerase chain reaction （FQ-PCR）. Markers were analyzed in the peripheral blood （PB） of 65 elderly patients （age 〉-65 years） with primary non-small cell lung cancer （NSCLC）, 20 younger patients （aged 〈55 years） with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, tumor group, and an elderly tumor group. The percentage an elderly healthy group, a young tumor group, a middle-aged of CD4＋CD25＋FoxP3＋ Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups. Results The percentage of peripheral CD4＋CD25＋CD127low Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4＋CD25＋CD127lowTregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis （TNM） staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4＋CD25＋FoxP3＋ Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice. Conclusions The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.展开更多
Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction （MI）. We studied the ...Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction （MI）. We studied the immunological characteristics and clinical impact of CD8＋CD57＋ T cells in acute MI patients. The frequency of CD57＋ cells among CD8＋ T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57＋ cells in the CD8＋ T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8＋CD57＋ T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8＋CD57＋ T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8＋CD57＋ T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8＋ T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8＋ T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.展开更多
Background The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence. It is well established...Background The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence. It is well established that CD28 and CD95 are associated with tumorgenesis and tumor progression, but the relationship between the age-related changes of these two immunological markers and cancer in the elderly is largely unknown. Methods The levels of CD28 and CD95 mRNA in peripheral blood mononuclear cells （PBMCs） from sixty-three elderly patients （aged 〉60 years） with primary non-small cell lung cancer （NSCLC） were analyzed by real-time fluorescence-based quantitative polymerase chain reaction （FQ-PCR）. In addition, twenty young patients （aged 〈60 years） with NSCLC, thirty elderly healthy donors and thirty young healthy donors were enrolled as controls. Results CD28 mRNA levels were significantly lower and CD95 mRNA levels were significantly higher in elderly patients with NSCLC than in the other groups. Similar results were found in elderly healthy donors comparing with young healthy donors. By Logistic regression analysis an increased risk of NSCLC was markedly associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95 mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA. In addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly patients was closely associated with the tumor node metastasis （TNM） stages, grade of cell differentiation and lymph node metastasis status, but not related to pathological types. Conclusions The results suggest a close relationship between T cell senescence and NSCLC tumour progress in the elderly, and that up-regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T cells may play an important role in inhibiting oncogenesis and development of primary NSCLC in the elderly.展开更多
Objective：To study the characteristics of lymphocyte nuclear factor kappa B（NF-κB） signal transduction kinase-related molecular mRNA differential expressions at various month age segments in aging process and the ...Objective：To study the characteristics of lymphocyte nuclear factor kappa B（NF-κB） signal transduction kinase-related molecular mRNA differential expressions at various month age segments in aging process and the intervening effect of Epimedium flavonoids（EF） on it.Methods：Sixty SD rats were divided into six groups,according to animals＇ age,i.e.,the 3 days（d） group,the 4 months（m） group,the 10 m group,the 18 m group,the 27 m group,and the 27 m＋EF group.RNA was extracted from separated splenic lymphocytes. Adopting NF-κB signal path functional genome oligonucleotide gene-chip（128 related genes）,the integral characteristics and differences of NF-κB signal transduction kinase-related mRNA expressions were determined, and the intervening effect of EF was examined.Results：The mean level of the NF-κB signal transduction kinase-related mRNA expressions in rats＇ splenic lymphocytes lowered with aging;the highest expression was presented at 3 d after birth,and then,it lowered gradually,with the lowest level at 18 m or 27 m.After EF intervention,the expression level was raised to the 10-18 m level in the aged rats.Conclusion：The changing rules of lymphocyte NF-κB-signal-transduction-kinase-related mRNA expressions in various stages of aging are helpful for selecting the well time for preventing and intervening aging,and will also give a hint to the molecular index for assessment of senility retarding researches.展开更多
基金supported by the National Natural Science Foundation of China (No.30330540)the Jiangsu Provincial Fund for Clinical Immunology Key Laboratory (No.200319)the Scientific and Technological Fund to Support Project of Suzhou City (ZS0901)
文摘Objective Age-related increment of the prevalence of CD4^＋CD25^＋ regulatory T （Treg） cells were described controversially, and whether such changes explain immune dysfunction in the elderly is still unclear. The aim of this systematic review is to evaluate the role of the Tregs in immunosenescence. Methods Medline and manual searches were performed to identify all published epidemiological and animal studies investigating the efficacy of the association between immunosenescence and Treg cells. Results It was founded that the frequency, phenotypic characteristics, and number/function of Tregs were altered significantly with aging. Medical conditions in individuals with advanced ageas well as apoptosis intensity of Treg cells had an impact on the accumulation of Tregs which in turn could deteriorate cytotoxic activity of CD8＋ T and NK cells and production of IL-2. The range of immune cells that could be suppressed by Treg cells was quite wide and covered CD4^＋CD25^＋ T cells, NK cells, dendritic cells and even monocytes. These changes were observed both in humans and experimental animals. Besides, it was believed that frequency of Tregs increased with age and was accompanied by intensified suppressive activity for Tregs in patients, for example, with Alzheimer disease （AD） and Parkinson disease （PD）. The impaired condition of CD4＋ T cells, so-called immunosenescence, rendered transplant recipients less responsive to an allogeneic kidney graft, an effect that was limited to transplant recipients who were aged over 60 years. Conclusions Treg cells are associated with immunosenescence. All these changes contribute to the aging-related decline of immune responses and lead to the higher risk of immune-mediated diseases, cancer or infections in aged individuals.
基金supported by a research grant(FFEP-CRP-08-002)from World Noni Research Foundation,Chennai,India
文摘Objective： Aging is associated with the development of diseases because of immunosuppression and altered functioning of the neuroendocrine system. The medicinal properties of Morinda citrifolia L. have been widely exploited for the treatment of age-associated diseases. This study aims to investigate the in vitro and in vivo effects of noni（M. citrifolia） fruit juice（NFJ） on neuro-immunomodulation in the lymph node lymphocytes of F344 rats.Methods： Lymphocytes isolated from axillary and inguinal lymph nodes of young（3–4 months） and old（18–21 months） rats were treated in vitro with different concentrations（0.0001%, 0.01%, and 1%） of NFJ for a period of 24 h. In the in vivo study, old（16–17 months） male F344 rats were treated with 5 mL/kg body weight of 5%, 10% and 20% of NFJ, twice a day, by oral gavage, and lymph node lymphocytes were isolated after 60 d. Concanavalin A（Con A）-induced lymphocyte proliferation, interleukin-2（IL-2）and interferon-γ（IFN-γ） production and expression of intracellular markers, such as phosphoextracellular signal-regulated kinase（p-ERK1/2）, phospho-γ AMP response element-binding protein,phospho-protein kinase B（p-Akt）, phospho-tyrosine hydroxylase（p-TH）, phospho-nuclear factor of κ light polypeptide gene enhancer in B-cells inhibitor-α（p-IκB-α） and phospho-nuclear factor-κB（p-NF-κB p65 and p50） were examined in the lymphocytes of lymph nodes.Results： NFJ increased Con A-induced lymphocyte proliferation, IL-2 and IFN-γ production, and p-ERK1/2 expression both in vitro and in vivo. In in vivo NFJ-treated old rats, lymph node lymphocytes showed increased expression of p-TH and Akt, nitric oxide production and decreased expression of p-NF-κB p65 and p50.Conclusion： These results suggest that the immunostimulatory properties of NFJ are facilitated through intracellular signaling pathways involving ERK1/2, Akt and NF-κB.
基金Supported by a grant from the University of Malaya Research Grant RG448-12HTM of the Health and Translational Medicine Research Cluster to Esaki M ShankarUM.C/625/1/HIR/Mo HE/MED/014 to Adeeba Kamarulzaman by the High Impact Research(HIR)+3 种基金University of Malaya,SIDA SARC,VINNMER for Vinnova,Linkping University Hospital Research Fund,CALF and the Swedish Society of Medicinethe Swedish International Development Cooperation Agencythe Swedish Physicians against AIDS Research Foundationthe Swedish Research Council,Marie Larsson,No.AI52731
文摘Immunosenescence is marked by accelerated degradation of host immune responses leading to the onset of opportunistic infections, where senescent T cells show remarkably higher ontogenic defects as compared to healthy T cells. The mechanistic association between T-cell immunosenescence and human immunodeficiency virus(HIV) disease progression, and functional T-cell responses in HIV-tuberculosis(HIV-TB) co-infection remains to be elaborately discussed. Here, we discussed the association of immunosenescence and chronic immune activation in HIV-TB co-infection and reviewed the role played by mediators of immune deterioration in HIV-TB coinfection necessitating the importance of designing therapeutic strategies against HIV disease progression and pathogenesis.
基金supported by the National Key Research and Development Program of China(2022YFF1100504)the 111 project from the Education Ministry of China(B18053)+2 种基金the National Natural Science Foundation of China(32101938 and 32302758)the China Postdoctoral Science Foundation(2022M723422)the Postdoctoral Fellowship Program of CPSF(GZB20230848).
文摘Susceptibility to pathogens in the elderly is heightened with age,largely because of immunosenescence.As an immune regulatory organ,bone marrow creates immune cells that move to other organs and tis-sues through the blood.Despite the significance of this process of this organ,there is limited research on changes in immune cell generation in the bone marrow and their effects on immunosenescence.In this study,the compositions of immune cells in bone marrow from young(three months)and old(24+months)mice were compared by means of mass cytometry,with further validation obtained through the reanalysis of single-cell RNA sequencing data and cell sorting via flow cytometry.The effects of differential immune cells on immunosenescence in old mice were evaluated using the Clostridium difficile(C.difficile)infection model.Our results showed that aged mice presented with a reduction in bone tra-beculae structure,which was accompanied by a notable increase in polymorphonuclear(PMN)-myeloid-derived suppressor cell(MDSC)abundance.Through bulk-seq and reverse transcription quantitative polymerase chain reaction(RT-qPCR)analysis,we identified differential genes associated with the immune response—specifically,the Th17 cell differentiation pathway.Furthermore,the increase in exported PMN-MDSCs to the large intestine resulted in increased gut permeability and inflammatory damage to the colon following C.difficile infection.After clearing the PMN-MDSCs in old mice using the anti-Gr-1 antibody,the symptoms induced by C.difficile were significantly relieved,as evidenced by an inhibited IL-17 pathway in the colon and reduced gut permeability.In conclusion,aging increases the number of PMN-MDSCs in both the generated bone marrow and the outputted intestine,which con-tributes to susceptibility to C.difficile infection.This study provides a novel target for anti-aging therapy for immunosenescence,which is beneficial for improving immune function in elders.
基金supported by the National Key R&D Program of China(2020YFA0710700,X.L.Y.)the National Science and Technology Major Projects of New Drugs(2018ZX09201018-013,P.C.)+1 种基金the National Key Research and Development Program of China(No.2023YFC3403303,P.C.)the National Natural Science Foundation of China Young Student Basic Research Program(823B2065,A.A.)。
文摘Immunosenescence refers to the abnormal activation or dysfunction of the immune system as people age.Inflammaging is a typical pathological inflammatory state associated with immunosenescence and is characterized by excessive expression of proinflammatory cytokines in aged immune cells.Chronic inflammation contributes to a variety of age-related diseases,such as neurodegenerative disease,cancer,infectious disease,and autoimmune diseases.Although not fully understood,recent studies contribute greatly to uncovering the underlying mechanisms of immunosenescence at the molecular and cellular levels.Immunosenescence is associated with dysregulated signaling pathways(e.g.,overactivation of the NF-κB signaling pathway and downregulation of the melatonin signaling pathway)and abnormal immune cell responses with functional alterations and phenotypic shifts.These advances remarkably promote the development of countermeasures against immunosenescence for the treatment of age-related diseases.Some anti-immunosenescence treatments have already shown promising results in clinical trials.In this review,we discuss the molecular and cellular mechanisms of immunosenescence and summarize the critical role of immunosenescence in the pathogenesis of age-related diseases.Potential interventions to mitigate immunosenescence,including reshaping immune organs,targeting different immune cells or signaling pathways,and nutritional and lifestyle interventions,are summarized.Some treatment strategies have already launched into clinical trials.This study aims to provide a systematic and comprehensive introduction to the basic and clinical research progress of immunosenescence,thus accelerating research on immunosenescence in related diseases and promoting the development of targeted therapy.
基金financially supported by the National Key R&D Program of China(2023YFE0116000,2023YFC2308300,2021YFC2301900)the National Natural Science Foundation of China(81771770,82071847,U23A20473,81974303,82350710801)+2 种基金Yunnan Key R&D Program(202403AC100011)the High-Level Public Health Specialized Talents Project of Beijing Municipal Health Commission(2022-2-018)Beijing Key Laboratory for HIV/AIDS Research(BZ0089).
文摘With the aging of the global population,older people living with HIV(OPLWH)have emerged as a focal point in HIV/AIDS research.Although antiretroviral therapy has demonstrated positive effects in OPLWH,concerns persist regarding overall poor immune reconstitution and elevated rates of age-related comorbidities,such as cardiovascular disease,bone disease,and cognitive impairment.This review aims to elucidate the mechanisms underlying immunosenescence and the interaction of immunosenescence with HIV infection,further exploring its role in the pathogenesis of HIV infection during aging.Aging-induced involution of the immune system,along with chronic inflammation and infection,can induce immunosenescence,leading to immune dysfunction that impairs the effective control of HIV infection.In addition,HIV infection induces immunosenescence through persistent inflammation and immune activation,even under treatment.The combined effects of aging and HIV infection accelerate the progression of immunosenescence in OPLWH,increasing their susceptibility to multiple age-related diseases.The unfavorable prognosis observed among OPLWH is largely attributed to increased levels of immunosenescence.A comprehensive understanding of the relationship between immunosenescence and HIV infection is crucial for developing targeted therapeutic strategies for this vulnerable population.
基金supported by multiyear research grant(MYRG)MYRG-GRG2023-00150-FHS-UMDF and MYRG-GRG2024-00146-FHS to K.M.by the University of Macao,Macao,China.
文摘Immunosenescence represents a natural process of immune degeneration that occurs with aging.Although this process is a common phenomenon in elderly patients,it extremely gets involved in tumor development and affects the clinical efficacy of cancer immunotherapy.Emerging studies demonstrate that improving immunosenescence may greatly enhance the efficacy and prognosis of cancer immunotherapy in elderly patients.However,limited clinical and preclinical studies have addressed immunosenescence as a therapeutic consideration,and the challenges of traditional cancer immunotherapy remain to be resolved.Nanomedicine,integrating nanotechnology and medicine,employs advanced nanomaterials and targeted drug delivery systems to achieve optimal region-specific biodistribution and therapeutic efficacy.This review systematically describes the various elements of immunosenescence and the impact on the vicious cycle between them and the tumor microenvironment.Meanwhile,based on a comprehensive understanding of the importance of immunosenescence in cancer formation and progression among elderly populations and the advantages of nanomedicine,we detail the feasibility of nanomedicine in improving immunosenescence to enhance cancer immunotherapy.Furthermore,this review also systematically discusses the synergistic mechanisms and clinical application prospects of nanomaterials with novel immunotherapy technologies,while also providing insights into the challenges and future directions in this field.In conclusion,this review provides comprehensive insights into the design and development of nanodrugs for improving immunosenescence,aiming to assist scientists who wish to expand their research scope and engage in this interdisciplinary field.
文摘Immunosenescence is described as a decline in the normal functioning of the immune system associated with physiologic ageing.Immunosenescence contributes to reduced efficacy to vaccination and increased susceptibility to infectious diseases in the elderly.Extensive studies of laboratory animal models of ageing or donor lymphocyte analysis have identified changes in immunity caused by the ageing process.Most of these studies have identified phenotypic and functional changes in innate and adaptive immunity.However,it is unclear which of these defects are critical for impaired immune defense against infection.This review describes the changes that occur in innate and adaptive immunity with ageing and some age-related viral diseases where defects in a key component of immunity contribute to the high mortality rate in mouse models of ageing.
基金This work was supported by the National Key Research and Development Program of China(No.2020YFC2002706)the Key Military Health Project(No.23BJZ25).
文摘Immune checkpoint inhibitors(ICIs)are employed in immunotherapeutic applications for patients with weakened immune systems and can improve the ability of T cells to kill cancer cells.Although ICIs can potentially treat different types of cancers in various groups of patients,their effectiveness may differ among older individuals.The reason ICIs are less effective in older adults is not yet clearly understood,but age-related changes in the immune system,such as immunosenescence and inflammation,may play a role.Therefore,this review focuses on recent advances in understanding the effects of immunosenescence and inflammation on the efficacy of ICIs.
基金supported by S&T Program of Hebei(No.23379902L).
文摘Myeloid-derived suppressor cells(MDSCs)are a group of heterogeneous immature cells with a strong immunosuppressive function in myeloid cells,which are impeded in the differentiation of myeloid cells under the pathological conditions of hypoxia,inflammation,infection,and cancer.As individuals age,there is a significant increase in myeloid-derived suppressor cells(MDSCs),which subsequently enhance the immunosuppressive functions of Tregs(regulatory T cells)and Bregs(regulatory B cells).Therefore,MDSC may be related to immune system remodeling,thereby preventing excessive lesions caused by aging.This indicates that MDSC could serve as a potent inducer of immune senescence.Immune senescence,characterized by immune dysfunction with aging,is closely linked to the onset of diseases like infections,pulmonary fibrosis,and tumors.To achieve the purpose of anti-aging by intervening in immune aging and slow down the occurrence and development of related diseases.Therefore,understanding the biological characteristics of MDSC and its role in immune aging is crucial for immunotherapy targeting MDSC.This article reviews the different roles of MDSC in immune aging and its relationship with pulmonary fibrosis,tumor and other related diseases to provide theoretical basis for more comprehensive targeted MDSC immunotherapy.
基金supported by joint funds for the innovation of science and technology,Fujian province(2020Y9027)Fujian Natural Science Foundation(2020J011062)Medical Innovation Project of Fujian Provincial Health Commission(2021CXA004).
文摘Objective:To investigate the effects of bone marrow-derived mesenchymal stem cells(BMSCs)on the proliferation and secretion of IgM,IgG and IL-2 in spleen lymphocytes(L)of aging rats.Methods:BMSCs were isolated by the whole bone marrow adherence method and characterized.A rat model of aging was produced by daily subcutaneous injection of D-galactose into the back of the neck.Rat spleen lymphocyte isolate kit to isolate spleen lymphocytes from aging rats and young rats.In vitro,the co-culture system of BMSCs and aging rats lymphocytes was established,and under the induction of mitogen LPS and ConA,the proliferative activity of lymphocytes in each group was detected by CCK-8 assay,the levels of IgM and IgG in the culture supernatant of each group was detected by ELISA,and the IL-2 radioimmunoassay kits were used to detect the content of IL-2 in the supernatant of each group.Results:(1)The isolated adherent cells showed the characteristics of BMSCs,including spindle-shaped morphology,high expression of CD29,CD44,low expression of CD34 and CD45,and osteogenic/adipogenic ability.(2)Under LPS induction,lymphocyte proliferative activity and secretion of immunoglobulin IgG were reduced in the aging group compared with the young group,and co-culture with BMSCs reversed this trend.(3)Under ConA induction,the IL-2 content of BMSCs co-cultured with aging lymphocytes was higher than that of aging lymphocytes alone(P<0.0001);the IL-2 content of CsA co-cultured with aging lymphocytes was lower than that of aging lymphocytes alone(P<0.0001).Conclusion:BMSCs have immunomodulatory effects on the spleen lymphocytes of aging rats in vitro.
基金National Institute of HealthDeep South Resource Center for Minority Aging Research (1P30AG031054-01, provided by the National Institute on Aging)
文摘Given the protective roles of 25-hydroxyvitamin D (25(OH)D or vitamin D) in musculoskeletal health and the potential beneficial effects of vitamin D supplementation in reducing the risk of various chronic diseases, intensive repletion of vitamin D has been widely advocated. Of note, CD8 T cells have the highest levels of the vitamin D receptor compared with other major immune cells. The effects of vitamin D on CD8 T cells during aging, however, remain unclear. This study determined the relationship between vitamin D levels and CD8 T cell status in 34 healthy female subjects (all >60 years old). The CD8 T-cell phenotype was defined by the surface expression of CD28 and CD95. The low-25(OH)D serum groups (≤30 ng/ml) had higher percentages of CD28+CD95–CD8+ (na?ve) T cells and lower percentages of CD28+CD95+CD8+ (effector) T cells. By contrast, subjects with high levels of 25(OH)D had very low percentages of na?ve CD8 T cells but very high percentages of effector CD8 T cells. There was a significant inverse correlation between 25(OH)D levels and the frequency of na?ve CD8 T cells. The results show that higher levels of vitamin D are correlated with decreased frequencies of na?ve CD8 T cells during early aging, suggesting that higher levels of 25(OH)D accelerate CD8 T cell senescence. These results warrant further evaluation of the effects of vitamin D supplementation in immune aging.
文摘Geriatric care during coronavirus disease 2019 is a real concern for all countries whether it is developed or developing.Poor tolerability for conventional medicines,co-morbidities,weak immune system,high oxidative stress,arterial aging,psychological stress and somatization are few possible reasons for high vulnerability of elderly people for coronavirus disease 2019.Beside high vulnerability of elderly people other major lacunas like improper nurturing,health care services,delayed in providing emergency treatment facilities are also major concern.Therefore it is require to make them self dependent and self sufficient in taking care for themselves by providing information of simple household remedies and simple life style measures that can be adopted easily,tolerable,accessible,affordable and above all safe to use.The article discusses simple spices that can be use as medicines for the management of coronavirus disease 2019 related diseases along with depiction of simple yogic techniques that can be performed indoor to maintain physical activity.
文摘Ageing is associated with several anatomical and physiological changes of the organism, and the increase in global elderly population promotes the research to develop strategies to improve their quality of life. In this work, we characterized the immunological alterations naturally produced during aging in a mice model, and evaluated the effect of probiotic Lactobacillus (L.) rhamnosus CRL1505 administration on those immunological parameters. We demonstrated that L. rhamosus CRL1505 was able to improve peritoneal macrophages phagocytic activity, and the number of intestinal IgA<sup>+</sup> cells in aged mice, reaching values of those parameters similar to young adult mice. The results of this work indicate that is plausible that the immunobiotic CRL1505 strain may find applications as a beneficial immunomodulator in aging to reinforce the intestinal and systemic immunity. The immune modulation in aging induced by L. rhamnosus CRL1505 could lead to the development of new strategies for functional foods specifically tailored for the elderly.
基金supported by the National Natural Science Foundation of China(No.82430123)the Joint Fund for Innovative Development of Shandong Natural Science Foundation(No.ZR2023LZY006,China)+1 种基金the Taishan Scholar Foundation of Shandong Province(No.tstp20221166,China)the National Administration of Traditional Chinese Medicine Science and Technology Department Science and Technology Joint Construction Project(No.GZY-KJS-SD-2023-023,China).
文摘The aging microenvironment,as a key driver of tumorigenesis and progression,plays a critical role in tumor immune regulation through one of its core features-the senescence-associated secretory phenotype(SASP).SASP consists of a variety of interleukins,chemokines,proteases,and growth factors.It initially induces surrounding cells to enter a state of senescence through paracrine mechanisms,thereby creating a sustained inflammatory stimulus and signal amplification effect within the tissue microenvironment.Furthermore,these secreted factors activate key signaling pathways such as NF-κB,cGAS-STING,and mTOR,which regulate the expression of immune-related molecules(such as PDL1)and promote the recruitment of immunosuppressive cells,including regulatory T cells and myeloid-derived suppressor cells.This process ultimately contributes to the formation of an immunosuppressive tumor microenvironment.Furthermore,the article explores potential anti-tumor immunotherapy strategies targeting SASP and its associated molecular mechanisms,including approaches to inhibit SASP secretion or eliminate senescent cells.Although these strategies have shown promise in certain tumor models,the high heterogeneity among tumor types may result in varied responses to SASP-targeted therapies.This highlights the need for further research into adaptive stratification and personalized treatment approaches.Targeting immune regulatory mechanisms in the aging microenvironment-particularly SASP-holds great potential for advancing future anti-tumor therapies.
基金Supported by Peking Union Medical College Hospital Research Fund for Young Investigators (Grant No. 2006108)the Specialized New Teacher Research Fund for the Doctoral Program of Higher Education of the Ministry of Education of China (Grant No. 20070023057)+3 种基金the National Basic Research Program of China (Grant No. 2006CB504204)the Therapeutic Drug Monitoring of Anti-HIV Regimens and HIV Resistance Testing in Beijing HIV/AIDS Patients Receiving HAART (Grant No. D0906003040491)Clinical Disciplines' Key Project of the Ministry of Health: the study on the clinical characteristics, virology and immune responses in AIDS patients receiving HAARTPeking Union Medical College Hospital Fok YingTung Specialized Research Fund for Lung Cancer
文摘This study was performed to build region-specific reference ranges of peripheral blood lymphocyte subsets for Chinese healthy adults from the young to the elderly and analyze the trends of changes in lymphocyte subsets for evaluating the impact of age on the values.151 healthy adults aged 19-86 were recruited based on the SENIEUR protocol.Three sets of reference ranges were finally built applicable for the healthy young(19-44 years),middle-aged(45-64 years) and elder adults(≥65).Comparisons in parameters among the three cohorts showed that a statistically significant increase in CD16CD56+ NK cell was observed between the middle-aged and elder cohorts,whereas for the majority of the parameters,a significant decline was observed between the young and the middle-aged cohorts.Further results showed that inverse correlations were observed between the age and CD19+ B,CD3+ T,CD3+CD4+ T,CD4+CD45RA+CD62L+ nave T cell and CD4+CD28+/CD4+,while the positive one was identified between the age and the NK cell.These significant changes of the most of immune parameters provided evidence for immunosenescence.Notably,T cell activation markers of CD8+CD38+ and CD8+HLA-DR+ showed reverse trends of association with age,which provides a clue for further researches on the mechanisms underlying the paradoxical clinical presentation of the elder patients.
文摘Background Immunosuppressive regulatory T cells （Tregs） participate in tumor immune evasion and the number and suppressive function of Tregs change with the aging process, but it is not clear whether such change leads to a higher incidence of tumors in the elderly. To this end, we designed experiments to explore the changes of Tregs and the functional gene Forkhead box P3 （FoxP3） in the aging process and its relationship with lung tumors in humans and mice. Methods The percentage of CD4＋CD25＋CD127lowTregs and expression of FoxP3 mRNA were analyzed using flow cytometry （FCM） and real-time fluorescence-based quantitative polymerase chain reaction （FQ-PCR）. Markers were analyzed in the peripheral blood （PB） of 65 elderly patients （age 〉-65 years） with primary non-small cell lung cancer （NSCLC）, 20 younger patients （aged 〈55 years） with NSCLC, 30 elderly healthy individuals and 30 young healthy individuals. Furthermore, we set up the Lewis lung cancer model with C57BL/6 female mice. Thirty-six mice were divided into a young healthy group, a middle-aged healthy group, tumor group, and an elderly tumor group. The percentage an elderly healthy group, a young tumor group, a middle-aged of CD4＋CD25＋FoxP3＋ Tregs and the expression level of FoxP3 mRNA in splenocytes were determined in the six groups. Results The percentage of peripheral CD4＋CD25＋CD127low Tregs and the expression of FoxP3 mRNA were significantly increased in elderly patients with NSCLC comparing with the other groups and in elderly healthy individuals compared with young healthy individuals. Further analysis showed that the percentage of CD4＋CD25＋CD127lowTregs and the expression of FoxP3 mRNA were closely associated with tumor node metastasis （TNM） staging in elderly patients with NSCLC. In the mouse model, the percentage of CD4＋CD25＋FoxP3＋ Tregs and the expression of FoxP3 mRNA in splenocytes of the tumor groups were significantly higher than in the healthy groups, with the highest expression in the elderly tumor group. In the healthy groups, the elderly healthy mice had the highest percentage of Tregs and expression of FoxP3 mRNA. The elderly mice had larger and heavier tumors than did the young and middle aged mice. Conclusions The up-regulation of Tregs and the FoxP3 gene with aging may play an essential role in oncogenesis and development of lung tumors in an elderly population.
文摘Although T cells are known to be involved in the pathogenesis of coronary artery disease, it is unclear which subpopulation of T cells contributes to pathogenesis in acute myocardial infarction （MI）. We studied the immunological characteristics and clinical impact of CD8＋CD57＋ T cells in acute MI patients. The frequency of CD57＋ cells among CD8＋ T cells was examined in peripheral blood sampled the morning after acute MI events. Interestingly, the frequency of CD57＋ cells in the CD8＋ T-cell population correlated with cardiovascular mortality 6 months after acute MI. The immunological characteristics of CD8＋CD57＋ T cells were elucidated by surface immunophenotyping, intracellular cytokine staining and flow cytometry. Immunophenotyping revealed that the CD8＋CD57＋ T cells were activated, senescent T cells with pro-inflammatory and tissue homing properties. Because a high frequency of CD8＋CD57＋ T cells is associated with short-term cardiovascular mortality in acute MI patients, this specific subset of CD8＋ T cells might contribute to acute coronary events via their pro-inflammatory and high cytotoxic capacities. Identification of a pathogenic CD8＋ T-cell subset expressing CD57 may offer opportunities for the evaluation and management of acute MI.
基金This study was supported by a grant from the National Natural Science Foundation of China （No. 30330540）.
文摘Background The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence. It is well established that CD28 and CD95 are associated with tumorgenesis and tumor progression, but the relationship between the age-related changes of these two immunological markers and cancer in the elderly is largely unknown. Methods The levels of CD28 and CD95 mRNA in peripheral blood mononuclear cells （PBMCs） from sixty-three elderly patients （aged 〉60 years） with primary non-small cell lung cancer （NSCLC） were analyzed by real-time fluorescence-based quantitative polymerase chain reaction （FQ-PCR）. In addition, twenty young patients （aged 〈60 years） with NSCLC, thirty elderly healthy donors and thirty young healthy donors were enrolled as controls. Results CD28 mRNA levels were significantly lower and CD95 mRNA levels were significantly higher in elderly patients with NSCLC than in the other groups. Similar results were found in elderly healthy donors comparing with young healthy donors. By Logistic regression analysis an increased risk of NSCLC was markedly associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95 mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA. In addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly patients was closely associated with the tumor node metastasis （TNM） stages, grade of cell differentiation and lymph node metastasis status, but not related to pathological types. Conclusions The results suggest a close relationship between T cell senescence and NSCLC tumour progress in the elderly, and that up-regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T cells may play an important role in inhibiting oncogenesis and development of primary NSCLC in the elderly.
基金Supported by the National Natural Science Foundation of China(No.30500681,30973845)Major State Basic Research Development Program of China(No.2007CB507406)Traditional Chinese Medicine Modernization Programs of Shanghai Science and Technology Committee(No.09dZ1975000)
文摘Objective：To study the characteristics of lymphocyte nuclear factor kappa B（NF-κB） signal transduction kinase-related molecular mRNA differential expressions at various month age segments in aging process and the intervening effect of Epimedium flavonoids（EF） on it.Methods：Sixty SD rats were divided into six groups,according to animals＇ age,i.e.,the 3 days（d） group,the 4 months（m） group,the 10 m group,the 18 m group,the 27 m group,and the 27 m＋EF group.RNA was extracted from separated splenic lymphocytes. Adopting NF-κB signal path functional genome oligonucleotide gene-chip（128 related genes）,the integral characteristics and differences of NF-κB signal transduction kinase-related mRNA expressions were determined, and the intervening effect of EF was examined.Results：The mean level of the NF-κB signal transduction kinase-related mRNA expressions in rats＇ splenic lymphocytes lowered with aging;the highest expression was presented at 3 d after birth,and then,it lowered gradually,with the lowest level at 18 m or 27 m.After EF intervention,the expression level was raised to the 10-18 m level in the aged rats.Conclusion：The changing rules of lymphocyte NF-κB-signal-transduction-kinase-related mRNA expressions in various stages of aging are helpful for selecting the well time for preventing and intervening aging,and will also give a hint to the molecular index for assessment of senility retarding researches.
