免疫系统的衰老及其机制

人体的衰老是生命过程中的自然规律,是机体中多细胞、多组织和多系统的进行性功能衰退状态.免疫系统的主要功能是维持机体的正常免疫功能,防御病原微生物的侵袭,增加人体对传染性疾病的抵抗力;同时能识别和清除体内衰老及癌变的细胞,发挥免疫监视及保持机体内环境稳定的重要功能.目前大量的研究发现人体衰老过程中免疫功能也明显衰退,导致许多与衰老有关疾病的发生,如肿瘤、自身免疫性疾病、中枢神经系统退行性疾病以及感染等.近年的研究揭示了免疫系统衰老导致一些老年性疾病发病的机制.本文着重阐述免疫系统的衰老及分子机制的近期研究进展.     

保护衰老的免疫系统以保持生活质量

研究者们在钻研衰老的过程时,发现相关的免疫系统损害颇为显著。这种认识有助于维持免疫活性及良好的生活质量,安然步入老年。     

衰老的生殖内分泌改变及其机制研究进展

衰老是人类在生命过程中整体的形态、结构和功能逐渐衰退现象的总称，是一个生殖成熟后才开始的持续的线性过程。人体衰老最根本的变化是男女更年期的来临。伴随生殖衰老所发生的性激素分泌及其调节机制的改变不仅导致生殖功能的减退，也和衰老的各种临床表现，如皮肤萎缩、骨质丢失、肌力降低等有关，甚至与许多老年疾病如动脉粥样硬化、老年性痴呆、肿瘤、肥胖等密切相关。有人对围绝经期妇女进行年龄估计并测定血清雌激素(E2)水平，发现血清E2水平与估计     

衰老的自由基机制

自由基是生物体新陈代谢过程中产生的一类具有氧化活性的带负电的离子,其化学性质相当活跃。数十年来人们对自由基的研究已深入到一个比较高的水平,认识到自由基的产生和机体对自由基的清除功能的动态平衡同人体的生理、病理、生长发育及疾病、衰老密切相关。衰老自由基学说使人们对衰老过程加强了认识,但目前的实验结果并不能完全解释自由基导致衰老的全部机制。有些问题,如自由基损伤的启动机制,不同自由基清除剂之间的相互作用,生理状态下的自由基生成与衰老过程中自由基生成的区别等还需要进一步研究。本文对近年来国内外对衰老和自由基…     

皮肤衰老的分子机制

<正>人们对于衰老的机制提出了许多学说,如衰老基因学说、自由基学说、线粒体学说、神经内分泌免疫网络学说及细胞凋亡学说、端粒学说等理论〔1〕。事实上是从不同角度来认识衰老的问题,既有机体的整体水平、也有器官水平,甚至涉及细胞水平、分子水平。一般将皮肤的衰老主要分为自然衰老和环境老化两种形式,其中日光紫外线(UV)长期反复的照射是环境中影响皮肤衰老的最重要因素,又称光老化。主要表现为暴露部位粗糙、皱纹加深加粗、不规则性色素沉着、血管扩张、表皮角     

衰老对肿瘤的影响及其作用机制

<正>衰老,即生物在生存期间自身机体形态、结构与功能朝着衰退方向发展的现象,衰老过程中由于基因突变增多、炎性反应加剧、免疫功能被削弱,进而诱发肿瘤的发生、发展及转移^[1-2]。首先,细胞周期的永久停滞称为细胞衰老,主要由端粒侵蚀、癌基因激活、氧自由基、化学物质和电离辐射等压力刺激引起^[3]。衰老细胞通过合成的白介素、生长因子、     

根据衰老机制的复杂性探讨衰老干预的新进展

<正>近Baker〔1〕报道衰老是造成人体许多慢性病的主因,其机制尚不够明确。细胞衰老机制能够抑制受损细胞的增殖,但随着年龄的增长,衰老的细胞积聚于各种组织和器官中,它们所分泌的物质可能会破坏组织结构和功能。Fred报道〔2〕衰老与增龄相关的老年慢性病实际上均属于衰老综合征的范畴,包括脑退行性性变、心血管疾病等。所以研究衰老机制不但有助于抗衰老及保健的研究与实践,而且对防治与增龄相关的老年病     

肾脏衰老机制的探讨

随着科学技术及医学的进步和发展,人口老龄化已成为当今社会面临的重要问题,预计到2030年,≥65岁的老年人口将达到目前人数的2倍,且与年龄相关疾病的发生率将随之升高。由于老龄化与发生肾脏疾病的风险相关,因此研究肾脏衰老相关机制,对于降低老年肾脏病发生率、延缓老年肾脏病发展有重要意义,同时也可减轻家庭、社会经济负担。本文旨在回顾既往发表文献,总结肾脏衰老的可能分子机制。     

衰老中宏、微量元素的变化规律及其作用机制

评价人体衰老程度,估计预期寿命涉及衰老过程中各项指标的变化规律。现就与衰老相关的某些宏、微量元素变化规律及其作用机制等做一简要概括。1关于衰老的概念及机制〔1,2〕由于衰老的本质目前尚未明确,因此,国内外至今难以给予衰老明确的定义,只能就现有认识提出若干概念,从不同学科(层面)概括衰老的内涵:其一,衰老是机体发育成熟后,随着时间的推移所出现的、多种因素联合作用的退行性变化及其功     

加味四君子汤对增龄大鼠免疫系统的调节作用及其初步机制探讨

目的 观察中药复方制剂加味四君子汤对增龄大鼠免疫系统功能的调节作用,并对可能的作用机制行初步探讨. 方法 选取50只12月龄健康Wistar大鼠,雌雄各半,随机分为5组,即加味四君子汤(以下简称药物)低剂量组、中剂量组、高剂量组,阳性对照组、老年对照组,每组各10只;另选取10只3月龄的Wistar大鼠作为青年对照组.各组分别给予加味四君子汤1.6、3.2、6.4 g/(kg·d),六味地黄丸混悬液1.5 g/(kg·d),2ml蒸馏水灌胃,持续给药90d.称量大鼠体重后处死,观察试验大鼠的血清免疫球蛋白(IgG)水平;计算胸腺指教、脾脏指数;将胸腺和脾脏组织进行HE染色,光镜下观察组织形态学改变;用免疫组化法检测胸腺白介素-2(IL-2)的表达情况及脾脏肿瘤坏死因子-α(TNF-α)的表达情况. 结果 与青年对照组相比较,各组大鼠血清IgG、胸腺IL-2、胸腺和脾脏指数均显著降低(P＜0.01),脾脏TNF-α表达水平均明显升高(P＜0.01);与老年对照组比较,药物组的IgG、胸腺IL-2、胸腺指数升高(P＜0.05或P＜0.01),脾脏TNF-α表达水平降低(P＜0.01).光镜下,药物组胸腺有不同程度的萎缩,胸腺组织被脂肪替代等病理变化程度降低,胸腺细胞分布较密,着色良好.脾脏的白髓分界欠清晰,白髓略微增多,中性粒细胞数量增多,淋巴细胞排列比较疏松. 结论 加味四君子汤通过细胞因子之间的相互调节作用,增加机体的体液免疫、控制机体的高炎性状态,从而延缓老龄大鼠的炎性免疫衰老.     

Responsiveness of the innate immune system and glucose concentrations in the oldest old

Patients with diabetes mellitus show increased risk of infectious disease as well as disturbances in innate immunity. In critical care settings, hyperglycemia is associated with increased risk of sepsis. It is unclear whether elevated glucose concentrations and innate immunity are associated in a non-clinical setting. We aimed to assess the association between glucose concentrations and innate immune response in the oldest old, who are at increased risk of both disturbed glucose metabolism as well as infectious disease. This study was part of the Leiden 85-plus Study. In 562 subjects aged 85 years old of the general population, venous blood samples were taken for measurement of morning glucose, C-reactive protein (CRP) and glycated hemoglobin (HbA1c). The innate immune response was assessed by performing ex vivo whole blood lipopolysaccharide (LPS) stimulation for production capacity of tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), interleukin 1-beta (IL1-β), interleukin 10 (IL-10) and interleukin 1 receptor antagonist (IL-1Ra). Using linear regression analysis, cross-sectional analysis between glucose and cytokine production capacity was performed. We found a significant negative association between glucose concentrations, but not HbA1c, and cytokine response capacity in four out of five measured cytokines (all p < 0.05). Both glucose and HbA1c were positively associated with circulating levels of CRP. Higher glucose concentrations in non-diabetic elderly are associated with lower innate immune response. As elderly show increased vulnerability for disturbances in glucose metabolism as well as infectious disease, this relation could be of clinical significance.     

Iron overload and immunity

Progress in the characterization of genes involved in the control of iron homeostasis in humans and in mice has improved the definition of iron overload and of the cells affected by it. The cell involved in iron overload with the greatest effect on immunity is the macrophage.Intriguing evidence has emerged, however, in the last 12 years indicating that parenchymal iron overload is linked to genes classically associated with the immune system. This review offers an update of the genes and proteins relevant to iron metabolism expressed in cells of the innate immune system, and addresses the question of how this system is affected in clinical situations of iron overload. The relationship between iron and the major cells of adaptive immunity, the T lymphocytes,will also be reviewed. Most studies addressing this last question in humans were performed in the clinical model of Hereditary Hemochromatosis. Data will also be reviewed demonstrating how the disruption of molecules essentially involved in adaptive immune responses result in the spontaneous development of iron overload and how they act as modifiers of iron overload.     

Toll样受体及其在抗结核感染免疫中的作用

Toll样受体(Toll-like receptors,TLR)是表达在哺乳动物细胞表面的一类重要的模式识别受体,是进化中比较保守的一个受体家族,TLR能特异地识别病原体相关分子模式,不仅在激活天然免疫中发挥着莺要的作用,而且还调节获得性免疫,是连接天然免疫与特异性免疫的主要桥梁.研究表明,TLR是介导宿主对结核杆菌的识别及抗结核免疫反应的关键分子,与抗结核感染免疫有关的主要是TLR2和TLR4.对TLR的研究有助于阐明结核病的发病机制并为其治疗提供崭新的策略.     

Immune reaction and colorectal cancer: Friends or foes?

The potential clinical impact of enhancing antitumor immunity is increasingly recognized in oncology therapeutics for solid tumors. Colorectal cancer is one of the most studied neoplasms for the tumor-host immunity relationship. Although immune cell populations involved in such a relationship and their prognostic role in colorectal cancer development have clearly been identified, still no approved therapies based on host immunity intensification have so far been introduced in clinical practice. Moreover, a recognized risk in enhancing immune reaction for colitis-associated colorectal cancer development has limited the emphasis of this approach. The aim of the present review is to discuss immune components involved in the host immune reaction against colorectal cancer and analyze the fine balance between pro-tumoral and anti-tumoral effect of immunity in this model of disease.     

Conditional inhibition of autophagy genes in adult Drosophila impairs immunity without compromising longevity

Immune function declines with age in Drosophila and humans, and autophagy is implicated in immune function. In addition, autophagy genes are required for life span extension caused by reduced insulin/IGF1-like signaling and dietary restriction in Caenorhabditiselegans. To test if the autophagy pathway might be limiting for immunity and/or life span in adult Drosophila, the Geneswitch system was used to cause conditional inactivation of the autophagy genes Atg5, Atg7 and Atg12 by RNAi. Conditional inhibition of Atg genes in adult flies reduced lysotracker staining of adult tissues, and reduced resistance to injected Escherichia coli, as evidenced by increased bacterial titers and reduced fly survival. However, survival of uninjected flies was unaffected by Atg gene inactivation. The data indicate that Atg gene activity is required for normal immune function in adult flies, and suggest that neither autophagy nor immune function are limiting for adult life span under typical laboratory conditions.     

Hepatitis C Recurrence after Orthotopic Liver Transplantation: Mechanisms and Management

Chronic Hepatitis C (HCV) infection is the leading indication for orthotopic liver transplantation and recurrence is nearly universal. Chronic HCV infection is frequently established through evasion of the innate immune system. Priming of adaptive immune responses modulate the severity and rate of fibrosis progression. Those with demonstrable viremia entering the transplant period uniformly suffer recurrence post-transplant. Progression to cirrhosis is accelerated post-transplant secondary to systemic immunosuppression. In addition, a number of factors, including donor, host, and viral characteristics, influence severity and rate of fibrosis progression. Interferon-based therapy, the previous standard of care, in those with advanced cirrhosis or post-transplant has been limited by a number of issues. These include a relative lack of efficacy and poor tolerability with higher incidence of infection and anemia. Recently, approval of direct acting antivirals have ushered in a new era in HCV therapeutics and have applicability in these special populations. Their use immediately prior to or post-transplant is expected to improve both morbidity and mortality.