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Ageing on the impact of distribution about preformed anti-HLA and anti-MICA antibody specificities in recipients prior to initial HSCT from East China. 年龄对华东地区初次造血干细胞移植前受者体内已形成的抗-HLA和抗-MICA抗体特异性分布的影响。
IF 7.9 2区 医学 Pub Date : 2024-02-20 DOI: 10.1186/s12979-024-00417-4
Qinqin Pan, Xiao Ma, Yajie You, Yuejiao Yu, Su Fan, Xiaoyan Wang, Mengyuan Wang, Ming Gao, Guangming Gong, Kourong Miao, Jie Shen, Xiaoyu Zhou

Background: With the development of Hematopoietic Stem Cell Transplantation (HSCT) technology, increasing numbers of elderly patients were undergoing allogeneic HSCT and elderly patients with hematologic malignancies could benefit most from it. Preformed donor-specific human leukocyte antigen (HLA) antibodies (DSA) were associated with graft failure in HLA-mismatched allogeneic HSCT and the absence of DSA was the main criterion of selecting the donor. Except for sensitization events such as transfusion, pregnancy or previous transplantation, ageing affects the humoral immune response both quantitatively and qualitatively. To evaluate the prevalence and distribution of anti-HLA and antibodies of MHC class I chain related antigens A (MICA) specificities in different age groups before initial HSCT would provide HLA and MICA specific antibody profiles under the impact of ageing, which could provide meaningful information in the process of selecting suitable HLA-mismatched donors by avoiding preformed DSA.

Results: There were no significant differences in the distribution of anti-HLA class I, class II and anti-MICA antibodies among the three age groups in this study except that a significant lower negative ratio of anti-HLA class I, class II antibodies and higher positive rate of MICA antibodies with maximum mean fluorescent intensity (MFI) > 5000 in the elderly than in young age group. The distribution of antibody specificities against HLA -A, -B, -C, -DR, -DQ, -DP and MICA antigens in the three age groups were generally consistent. The anti-HLA class I antibody specificities with higher frequencies were A80,A68;B76,B45;Cw17, which were unlikely to become DSA in Chinese. Anti-HLA class II antibody specificities were more likely to become potential DSA than class I.DR7, DR9, DQ7, DQ8 and DQ9 were most likely to become potential DSA.

Conclusions: The prevalence of anti-HLA and anti-MICA antibodies increased slightly as age increased. While ageing had a small impact on the distribution of antibody specificity frequencies against HLA-A, -B, -C, -DR,-DQ, -DP and MICA antigens in recipients awaiting initial HSCT from East China. The risk of developing preformed DSA was basically consistent in the three age groups and the elderly group might be more favorable in HLA-mismatched HSCT due to higher positive rate of anti-MICA antibody.

背景:随着造血干细胞移植(HSCT)技术的发展,越来越多的老年患者开始接受异基因造血干细胞移植,而老年血液恶性肿瘤患者从中获益最大。在 HLA 不匹配的异基因造血干细胞移植中,预先形成的供体特异性人类白细胞抗原(HLA)抗体(DSA)与移植失败有关,而无 DSA 是选择供体的主要标准。除输血、妊娠或既往移植等致敏事件外,年龄的增长会从数量和质量上影响体液免疫反应。在初次造血干细胞移植前评估不同年龄组的抗 HLA 和 MHC I 类链相关抗原 A(MICA)特异性抗体的流行率和分布情况,可提供在老龄化影响下的 HLA 和 MICA 特异性抗体概况,从而为避免预先进行 DSA 以选择合适的 HLA 不匹配供体提供有意义的信息:结果:抗 HLA I 类、II 类和抗 MICA 抗体的分布在三个年龄组中无明显差异,但老年人抗 HLA I 类、II 类抗体的阴性率明显低于年轻人,而 MICA 抗体的阳性率(最大平均荧光强度(MFI)> 5000)则高于年轻人。三个年龄组针对 HLA -A、-B、-C、-DR、-DQ、-DP 和 MICA 抗原的抗体特异性分布基本一致。抗 HLA I 类抗体特异性较高的是 A80、A68;B76、B45;Cw17,这些抗体在中国人中不太可能成为 DSA。DR7、DR9、DQ7、DQ8和DQ9最有可能成为潜在的DSA:结论:随着年龄的增长,抗-HLA 和抗-MICA 抗体的流行率略有上升。结论:在华东地区等待初次造血干细胞移植的受者中,抗HLA和抗MICA抗体的发生率随着年龄的增长而略有增加,但年龄对HLA-A、-B、-C、-DR、-DQ、-DP和MICA抗原抗体特异性频率的分布影响较小。三个年龄组发生先形成的DSA的风险基本一致,老年组由于抗MICA抗体阳性率较高,可能更有利于HLA不匹配造血干细胞移植。
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引用次数: 0
The interplay between obesity, immunosenescence, and insulin resistance 肥胖、免疫衰老和胰岛素抵抗之间的相互作用
IF 7.9 2区 医学 Pub Date : 2024-02-05 DOI: 10.1186/s12979-024-00414-7
Ghazaleh Shimi, Mohammad Hassan Sohouli, Arman Ghorbani, Azam Shakery, Hamid Zand
Obesity, which is the accumulation of fat in adipose tissue, has adverse impacts on human health. Obesity-related metabolic dysregulation has similarities to the metabolic alterations observed in aging. It has been shown that the adipocytes of obese individuals undergo cellular aging, known as senescence. Senescence can be transmitted to other normal cells through a series of chemical factors referred to as the senescence-associated secretory phenotype (SASP). Most of these factors are pro-inflammatory compounds. The immune system removes these senescent T-cells, but immunosenescence, which is the senescence of immune cells, disrupts the clearance of senescent T-cells. Immunosenescence occurs as a result of aging or indirectly through transmission from senescent tissues. The significant occurrence of senescence in obesity is expected to cause immunosenescence and impairs the immune response to resolve inflammation. The sustained and chronic inflammation disrupts insulin's metabolic actions in metabolic tissues. Therefore, this review focuses on the role of senescent adipocyte cells in obesity-associated immunosenescence and subsequent metabolic dysregulation. Moreover, the article suggests novel therapeutic approaches to improve metabolic syndrome by targeting senescent T-cells or using senotherapeutics.
肥胖是脂肪组织中脂肪的堆积,对人体健康有不利影响。与肥胖相关的新陈代谢失调与衰老过程中观察到的新陈代谢改变有相似之处。研究表明,肥胖者的脂肪细胞会发生细胞衰老,即所谓的衰老。衰老可通过一系列称为衰老相关分泌表型(SASP)的化学因子传递给其他正常细胞。这些因子大多是促炎化合物。免疫系统会清除这些衰老的 T 细胞,但免疫衰老(即免疫细胞的衰老)会破坏衰老 T 细胞的清除。免疫衰老是衰老的结果,或通过衰老组织的间接传播而发生。肥胖症中衰老的大量发生预计会导致免疫衰老,并损害免疫反应以解决炎症。持续的慢性炎症会破坏胰岛素在代谢组织中的代谢作用。因此,这篇综述重点探讨了衰老脂肪细胞在肥胖相关免疫衰老和随后的代谢失调中的作用。此外,文章还提出了针对衰老 T 细胞或使用衰老治疗药物来改善代谢综合征的新型治疗方法。
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引用次数: 0
The role of NLRP3 inflammasome in aging and age-related diseases NLRP3 炎症小体在衰老和老年相关疾病中的作用
IF 7.9 2区 医学 Pub Date : 2024-02-05 DOI: 10.1186/s12979-023-00395-z
Ruikai Liang, Xinrui Qi, Qi Cai, Liyan Niu, Xi Huang, Deju Zhang, Jitao Ling, Yuting Wu, Yixuan Chen, Pingping Yang, Jianping Liu, Jing Zhang, Peng Yu
The gradual aging of the global population has led to a surge in age-related diseases, which seriously threaten human health. Researchers are dedicated to understanding and coping with the complexities of aging, constantly uncovering the substances and mechanism related to aging like chronic low-grade inflammation. The NOD-like receptor protein 3 (NLRP3), a key regulator of the innate immune response, recognizes molecular patterns associated with pathogens and injury, initiating an intrinsic inflammatory immune response. Dysfunctional NLRP3 is linked to the onset of related diseases, particularly in the context of aging. Therefore, a profound comprehension of the regulatory mechanisms of the NLRP3 inflammasome in aging-related diseases holds the potential to enhance treatment strategies for these conditions. In this article, we review the significance of the NLRP3 inflammasome in the initiation and progression of diverse aging-related diseases. Furthermore, we explore preventive and therapeutic strategies for aging and related diseases by manipulating the NLRP3 inflammasome, along with its upstream and downstream mechanisms.
全球人口逐渐老龄化,导致老年相关疾病激增,严重威胁人类健康。研究人员致力于了解和应对衰老的复杂性,不断揭示与衰老相关的物质和机制,如慢性低度炎症。NOD 样受体蛋白 3(NLRP3)是先天性免疫反应的关键调节因子,它能识别与病原体和损伤相关的分子模式,启动内在炎症免疫反应。功能失调的 NLRP3 与相关疾病的发病有关,尤其是在衰老的背景下。因此,深刻理解 NLRP3 炎性体在衰老相关疾病中的调控机制,有可能加强这些疾病的治疗策略。在本文中,我们回顾了 NLRP3 炎症小体在多种衰老相关疾病的发生和发展过程中的重要作用。此外,我们还探讨了通过操纵 NLRP3 炎性体及其上下游机制来预防和治疗衰老及相关疾病的策略。
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引用次数: 0
Monocyte alteration in elderly hip fracture healing: monocyte promising role in bone regeneration 老年髋部骨折愈合过程中单核细胞的改变:单核细胞在骨再生中有望发挥作用
IF 7.9 2区 医学 Pub Date : 2024-02-03 DOI: 10.1186/s12979-024-00413-8
Clement Shema, Yining Lu, Ling Wang, Yingze Zhang
Individual aged with various change in cell and cellular microenvironments and the skeletal system undergoes physiological changes that affect the process of bone fracture healing. These changes are accompanied by alterations in regulating critical genes involved in this healing process. Unfortunately, the elderly are particularly susceptible to hip bone fractures, which pose a significant burden associated with higher morbidity and mortality rates. A notable change in older adults is the increased expression of activation, adhesion, and migration markers in circulating monocytes. However, there is a decrease in the expression of co-inhibitory molecules. Recently, research evidence has shown that the migration of specific monocyte subsets to the site of hip fracture plays a crucial role in bone resorption and remodeling, especially concerning age-related factors. In this review, we summarize the current knowledge about uniqueness characteristics of monocytes, and their potential regulation and moderation to enhance the healing process of hip fractures. This breakthrough could significantly contribute to the comprehension of aging process at a fundamental aging mechanism through this initiative would represent a crucial stride for diagnosing and treating age related hip fracture.
随着年龄的增长,细胞和细胞微环境会发生各种变化,骨骼系统也会发生影响骨折愈合过程的生理变化。这些变化伴随着参与这一愈合过程的关键基因调控的改变。不幸的是,老年人特别容易发生髋部骨折,这给他们带来了沉重的负担,发病率和死亡率都较高。老年人的一个显著变化是循环单核细胞中活化、粘附和迁移标记物的表达增加。然而,辅助抑制分子的表达却有所减少。最近的研究证据表明,特定单核细胞亚群向髋部骨折部位的迁移在骨吸收和重塑中起着至关重要的作用,尤其是与年龄相关的因素。在这篇综述中,我们总结了目前有关单核细胞独特性特征的知识,以及对其进行潜在调节和控制以促进髋部骨折愈合过程的知识。这一突破将大大有助于从根本上理解衰老过程,为诊断和治疗与年龄相关的髋部骨折迈出关键一步。
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引用次数: 0
Antibody and transcription landscape in peripheral blood mononuclear cells of elderly adults over 70 years of age with third dose of COVID-19 BBIBP-CorV and ZF2001 booster vaccine. 接种第三剂 COVID-19 BBIBP-CorV 和 ZF2001 强化疫苗的 70 岁以上老年人外周血单核细胞中的抗体和转录图谱。
IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-01-27 DOI: 10.1186/s12979-023-00408-x
Yuwei Zhang, Lianxiang Zhao, Jinzhong Zhang, Xiaomei Zhang, Shanshan Han, Qingshuai Sun, Mingxiao Yao, Bo Pang, Qing Duan, Xiaolin Jiang

Background: In the context of the COVID-19 pandemic and extensive vaccination, it is important to explore the immune response of elderly adults to homologous and heterologous booster vaccines of COVID-19. At this point, we detected serum IgG antibodies and PBMC sample transcriptome profiles in 46 participants under 70 years old and 25 participants over 70 years old who received the third dose of the BBIBP-CorV and ZF2001 vaccines.

Results: On day 7, the antibody levels of people over 70 years old after the third dose of booster vaccine were lower than those of young people, and the transcriptional responses of innate and adaptive immunity were also weak. The age of the participants showed a significant negative correlation with functions related to T-cell differentiation and costimulation. Nevertheless, 28 days after the third dose, the IgG antibodies of elderly adults reached equivalence to those of younger adults, and immune-related transcriptional regulation was significantly improved. The age showed a significant positive correlation with functions related to "chemokine receptor binding", "chemokine activity", and "chemokine-mediated signaling pathway".

Conclusions: Our results document that the response of elderly adults to the third dose of the vaccine was delayed, but still able to achieve comparable immune effects compared to younger adults, in regard to antibody responses as well as at the transcript level.

背景:在 COVID-19 大流行和广泛接种疫苗的背景下,探索老年人对 COVID-19 的同源和异源强化疫苗的免疫反应非常重要。为此,我们检测了接种第三剂 BBIBP-CorV 和 ZF2001 疫苗的 46 名 70 岁以下参与者和 25 名 70 岁以上参与者的血清 IgG 抗体和 PBMC 样本转录组图谱:结果:接种第三剂加强疫苗后第7天,70岁以上老年人的抗体水平低于年轻人,先天性免疫和适应性免疫的转录反应也较弱。参与者的年龄与 T 细胞分化和成本刺激相关功能呈显著负相关。然而,在服用第三剂 28 天后,老年人的 IgG 抗体达到了年轻人的水平,与免疫相关的转录调控也得到了明显改善。年龄与 "趋化因子受体结合"、"趋化因子活性 "和 "趋化因子介导的信号通路 "相关功能呈显著正相关:我们的研究结果表明,老年人对第三剂疫苗的反应有所延迟,但在抗体反应和转录物水平上仍能达到与年轻人相当的免疫效果。
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引用次数: 0
Chitosan alleviates ovarian aging by enhancing macrophage phagocyte-mediated tissue homeostasis. 壳聚糖通过增强巨噬细胞吞噬细胞介导的组织稳态来缓解卵巢衰老。
IF 5.2 2区 医学 Q1 GERIATRICS & GERONTOLOGY Pub Date : 2024-01-27 DOI: 10.1186/s12979-024-00412-9
Hui-Hui Shen, Xin-Yan Zhang, Nan Liu, Yang-Yang Zhang, Hui-Hua Wu, Feng Xie, Wen-Jun Wang, Ming-Qing Li

Background: Age-related changes in the ovarian microenvironment are linked to impaired fertility in women. Macrophages play important roles in ovarian tissue homeostasis and immune surveillance. However, the impact of aging on ovarian macrophage function and ovarian homeostasis remains poorly understood.

Methods: Senescence-associated beta-galactosidase staining, immunohistochemistry, and TUNEL staining were used to assess senescence and apoptosis, respectively. Flow cytometry was employed to evaluate mitochondrial membrane potential (MMP) and apoptosis in granulosa cells lines (KGN), and macrophages phagocytosis. After a 2-month treatment with low molecular weight Chitosan (LMWC), ovarian tissues from mice were collected for comprehensive analysis.

Results: Compared with the liver and uterus, the ovary displayed accelerated aging in an age-dependent manner, which was accompanied by elevated levels of inflammatory factors and apoptotic cells, and impaired macrophage phagocytic activity. The aged KGN cells exhibited elevated reactive oxygen species (ROS) and apoptotic levels alongside decreased MMP. H2O2-induced aging macrophages showed reduced phagocytosis function. Moreover, there were excessive aging macrophages with impaired phagocytosis in the follicular fluid of patients with diminished ovarian reserve (DOR). Notably, LMWC administration alleviated ovarian aging by enhancing macrophage phagocytosis and promoting tissue homeostasis.

Conclusions: Aging ovarian is characterized by an accumulation of aging and apoptotic granulosa cells, an inflammatory response and macrophage phagocytosis dysfunction. In turn, impaired phagocytosis of macrophage contributes to insufficient clearance of aging and apoptotic granulosa cells and the increased risk of DOR. Additionally, LMWC emerges as a potential therapeutic strategy for age-related ovarian dysfunction.

背景:卵巢微环境中与年龄相关的变化与女性生育能力受损有关。巨噬细胞在卵巢组织稳态和免疫监视中发挥着重要作用。然而,人们对衰老对卵巢巨噬细胞功能和卵巢稳态的影响仍知之甚少:方法:采用衰老相关的β-半乳糖苷酶染色法、免疫组化法和TUNEL染色法分别评估衰老和细胞凋亡。流式细胞术用于评估粒细胞系(KGN)的线粒体膜电位(MMP)和凋亡情况,以及巨噬细胞的吞噬能力。用低分子量壳聚糖(LMWC)治疗 2 个月后,收集小鼠卵巢组织进行综合分析:结果:与肝脏和子宫相比,卵巢的衰老速度呈年龄依赖性,伴随着炎症因子和凋亡细胞水平的升高,以及巨噬细胞吞噬活性的减弱。老化的KGN细胞表现出活性氧(ROS)和细胞凋亡水平升高,同时MMP下降。H2O2- 诱导的老化巨噬细胞的吞噬功能降低。此外,在卵巢储备功能减退(DOR)患者的卵泡液中存在过多的老化巨噬细胞,其吞噬功能受损。值得注意的是,服用低密度脂蛋白胆固醇可通过增强巨噬细胞的吞噬功能和促进组织稳态来缓解卵巢衰老:结论:衰老卵巢的特征是衰老和凋亡颗粒细胞的积累、炎症反应和巨噬细胞吞噬功能障碍。反过来,巨噬细胞吞噬功能受损也会导致衰老和凋亡的颗粒细胞清除不足,增加罹患 DOR 的风险。此外,低密度脂蛋白胆固醇还可作为一种潜在的治疗策略,用于治疗与年龄有关的卵巢功能障碍。
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引用次数: 0
sCD163, sCD28, sCD80, and sCTLA-4 as soluble marker candidates for detecting immunosenescence. sCD163、sCD28、sCD80 和 sCTLA-4 作为检测免疫衰老的可溶性候选标记物。
IF 7.9 2区 医学 Pub Date : 2024-01-20 DOI: 10.1186/s12979-023-00405-0
Andrea Aprilia, Kusworini Handono, Hidayat Sujuti, Akhmad Sabarudin, Nuning Winaris

Background: Inflammaging, the characteristics of immunosenescence, characterized by continuous chronic inflammation that could not be resolved. It is not only affect older people but can also occur in young individuals, especially those suffering from chronic inflammatory conditions such as autoimmune disease, malignancy, or chronic infection. This condition led to altered immune function and as consequent immune function is reduced. Detection of immunosenescence has been done by examining the immune risk profile (IRP), which uses flow cytometry. These tests are not always available in health facilities, especially in developing countries and require fresh whole blood samples. Therefore, it is necessary to find biomarkers that can be tested using stored serum to make it easier to refer to the examination. Here we proposed an insight for soluble biomarkers which represented immune cells activities and exhaustion, namely sCD163, sCD28, sCD80, and sCTLA-4. Those markers were reported to be elevated in chronic diseases that caused early aging and easily detected from serum samples using ELISA method, unlike IRP. Therefore, we conclude these soluble markers are beneficial to predict pathological condition of immunosenescence.

Aim: To identify soluble biomarkers that could replace IRP for detecting immunosenescence.

Conclusion: Soluble costimulatory molecule suchsCD163, sCD28, sCD80, and sCTLA-4 are potential biomarkers for detecting immunosenescence.

背景:炎症是免疫衰老的特征,其特点是持续的慢性炎症无法消除。它不仅影响老年人,也可能发生在年轻人身上,尤其是那些患有慢性炎症的人,如自身免疫性疾病、恶性肿瘤或慢性感染。这种情况导致免疫功能改变,免疫功能随之降低。检测免疫衰老的方法是使用流式细胞仪检测免疫风险谱(IRP)。这些检测并不总能在医疗机构中进行,尤其是在发展中国家,而且需要新鲜的全血样本。因此,有必要找到可使用储存血清进行检测的生物标志物,以便于参考检查。在此,我们提出了一种代表免疫细胞活性和衰竭的可溶性生物标志物,即 sCD163、sCD28、sCD80 和 sCTLA-4。据报道,这些标志物在导致早衰的慢性疾病中会升高,而且与 IRP 不同,它们很容易用 ELISA 方法从血清样本中检测出来。因此,我们认为这些可溶性标记物有利于预测免疫衰老的病理状况:结论:CD163、sCD28、sCD80 和 sCTLA-4 等可溶性成本调节分子是检测免疫衰老的潜在生物标志物。
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引用次数: 0
Correction: A genomic perspective of the aging human and mouse lung with a focus on immune response and cellular senescence 更正:从基因组角度看人类和小鼠肺部的衰老,重点关注免疫反应和细胞衰老
IF 7.9 2区 医学 Pub Date : 2024-01-16 DOI: 10.1186/s12979-023-00407-y
Meng He, Jürgen Borlak

Correction: Immun Ageing 20, 58 (2023)

https://doi.org/10.1186/s12979-023-00373-5

Following publication of the original article [1], the authors reported an error in the HTML version of this article. The graphical abstract displayed is not the correct image but, a copy of Fig. 10 and in addition Fig. 11 is not fully displayed.

The publishers apologise for this error.

The original article [1] has been updated.

  1. He M, Borlak J. A genomic perspective of the aging human and mouse lung with a focus on immune response and cellular senescence. Immun Ageing. 2023;20:58. https://doi.org/10.1186/s12979-023-00373-5.

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  1. Centre for Pharmacology and Toxicology, Hannover Medical School, Carl‑Neuberg‑Str. 1, 30625, Hannover, Germany

    Meng He & Jürgen Borlak

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更正:Immun Ageing 20, 58 (2023)https://doi.org/10.1186/s12979-023-00373-5Following 原文[1]发表后,作者报告了本文 HTML 版本中的一处错误。He M, Borlak J. A genomic perspective of the aging human and mouse lung with a focus on immune response and cellular senescence. Immun Ageing.Immun Ageing.2023;20:58. https://doi.org/10.1186/s12979-023-00373-5.Article CAS PubMed PubMed Central Google Scholar 下载参考文献作者和单位汉诺威医学院药理学和毒理学中心,Carl-Neuberg-Str.1, 30625, Hannover, GermanyMeng He & Jürgen Borlak作者Meng He查看作者发表的文章您也可以在PubMed Google Scholar中搜索该作者Jürgen Borlak查看作者发表的文章您也可以在PubMed Google Scholar中搜索该作者通讯作者致Jürgen Borlak.Publisher's NoteSpringer Nature对出版地图和机构隶属关系中的管辖权主张保持中立。本文采用知识共享署名 4.0 国际许可协议(Creative Commons Attribution 4.0 International License)进行许可,允许以任何媒介或格式使用、共享、改编、分发和复制,但需注明原作者和来源,提供知识共享许可协议的链接,并说明是否进行了修改。本文中的图片或其他第三方材料均包含在文章的知识共享许可协议中,除非在材料的署名栏中另有说明。如果材料未包含在文章的知识共享许可协议中,且您打算使用的材料不符合法律规定或超出许可使用范围,则您需要直接从版权所有者处获得许可。要查看该许可的副本,请访问 http://creativecommons.org/licenses/by/4.0/。除非在数据的信用行中另有说明,否则创作共用公共领域专用免责声明 (http://creativecommons.org/publicdomain/zero/1.0/) 适用于本文提供的数据。转载与许可引用本文He, M., Borlak, J. Correction:以免疫反应和细胞衰老为重点的人肺和小鼠肺衰老的基因组视角。Immun Ageing 21, 8 (2024). https://doi.org/10.1186/s12979-023-00407-yDownload citationPublished: 16 January 2024DOI: https://doi.org/10.1186/s12979-023-00407-yShare this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard Provided by the Springer Nature SharedIt content-sharing initiative.
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引用次数: 0
Growth and longevity modulation through larval environment mediate immunosenescence and immune strategy of Tenebrio molitor. 幼虫环境对生长和寿命的调节介导了 Tenebrio molitor 的免疫衰老和免疫策略。
IF 7.9 2区 医学 Pub Date : 2024-01-12 DOI: 10.1186/s12979-023-00409-w
Agathe Crosland, Thierry Rigaud, Charlène Develay, Yannick Moret

Background: The Disposable Soma Theory of aging suggests a trade-off between energy allocation for growth, reproduction and somatic maintenance, including immunity. While trade-offs between reproduction and immunity are well documented, those involving growth remain under-explored. Rapid growth might deplete resources, reducing investment in maintenance, potentially leading to earlier or faster senescence and a shorter lifespan. However, rapid growth could limit exposure to parasitism before reaching adulthood, decreasing immunity needs. The insect immunity's components (cellular, enzymatic, and antibacterial) vary in cost, effectiveness, and duration. Despite overall immunity decline (immunosenescence), its components seem to age differently. We hypothesize that investment in these immune components is adjusted based on the resource cost of growth, longevity, and the associated risk of parasitism.

Results: We tested this hypothesis using the mealworm beetle, Tenebrio molitor as our experimental subject. By manipulating the larval environment, including three different temperatures and three relative humidity levels, we achieved a wide range of growth durations and longevities. Our main focus was on the relationship between growth duration, longevity, and specific immune components: hemocyte count, phenoloxidase activity, and antibacterial activity. We measured these immune parameters both before and after exposing the individuals to a standard bacterial immune challenge, enabling us to assess immune responses. These measurements were taken in both young and older adult beetles. Upon altering growth duration and longevity by modifying larval temperature, we observed a more pronounced investment in cellular and antibacterial defenses among individuals with slow growth and extended lifespans. Intriguingly, slower-growing and long-lived beetles exhibited reduced enzymatic activity. Similar results were found when manipulating larval growth duration and adult longevity through variations in relative humidity, with a particular focus on antibacterial activity.

Conclusion: The impact of growth manipulation on immune senescence varies by the specific immune parameter under consideration. Yet, in slow-growing T. molitor, a clear decline in cellular and antibacterial immune responses with age was observed. This decline can be linked to their initially stronger immune response in early life. Furthermore, our study suggests an immune strategy favoring enhanced antibacterial activity among slow-growing and long-lived T. molitor individuals.

背景:一次性躯体衰老理论认为,生长、繁殖和躯体维持(包括免疫)的能量分配之间需要权衡。尽管生殖和免疫之间的权衡已被充分记录,但涉及生长的权衡仍未得到充分探讨。快速生长可能会耗尽资源,减少对维持的投资,从而可能导致更早或更快的衰老和更短的寿命。不过,快速生长可能会限制昆虫在成年之前接触寄生虫的机会,从而降低免疫需求。昆虫免疫的组成部分(细胞、酶和抗菌)在成本、有效性和持续时间方面各不相同。尽管整体免疫力下降(免疫衰老),但其组成部分的衰老程度似乎不同。我们假设,对这些免疫成分的投资是根据生长、寿命和相关寄生虫风险的资源成本进行调整的:我们使用黄粉虫甲虫作为实验对象来验证这一假设。通过调节幼虫的生长环境,包括三种不同的温度和三种相对湿度水平,我们获得了不同的生长期和寿命。我们的主要研究重点是生长时间、寿命和特定免疫成分(血细胞计数、酚氧化酶活性和抗菌活性)之间的关系。我们在个体接受标准细菌免疫挑战之前和之后测量了这些免疫参数,从而评估了免疫反应。这些测量都是在年轻和年老的成年甲虫身上进行的。在通过改变幼虫温度来改变生长持续时间和寿命后,我们观察到生长缓慢和寿命较长的个体在细胞和抗菌防御方面的投入更为明显。耐人寻味的是,生长速度慢和寿命长的甲虫表现出酶活性降低。在通过改变相对湿度来控制幼虫生长时间和成虫寿命时,也发现了类似的结果,尤其是在抗菌活性方面:结论:生长控制对免疫衰老的影响因所考虑的具体免疫参数而异。然而,在生长缓慢的褐飞虱身上,我们观察到细胞和抗菌免疫反应随着年龄的增长而明显下降。这种衰退可能与它们早期较强的免疫反应有关。此外,我们的研究还表明,生长缓慢的长寿褐飞虱个体的免疫策略有利于增强抗菌活性。
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引用次数: 0
Accelarated immune ageing is associated with COVID-19 disease severity 免疫加速老化与 COVID-19 疾病的严重程度有关
IF 7.9 2区 医学 Pub Date : 2024-01-11 DOI: 10.1186/s12979-023-00406-z
Janet M. Lord, Tonny Veenith, Jack Sullivan, Archana Sharma-Oates, Alex G. Richter, Neil J. Greening, Hamish J. C. McAuley, Rachael A. Evans, Paul Moss, Shona C. Moore, Lance Turtle, Nandan Gautam, Ahmed Gilani, Manan Bajaj, Louise V. Wain, Christopher Brightling, Betty Raman, Michael Marks, Amisha Singapuri, Omer Elneima, Peter J. M. Openshaw, Niharika A. Duggal
The striking increase in COVID-19 severity in older adults provides a clear example of immunesenescence, the age-related remodelling of the immune system. To better characterise the association between convalescent immunesenescence and acute disease severity, we determined the immune phenotype of COVID-19 survivors and non-infected controls. We performed detailed immune phenotyping of peripheral blood mononuclear cells isolated from 103 COVID-19 survivors 3–5 months post recovery who were classified as having had severe (n = 56; age 53.12 ± 11.30 years), moderate (n = 32; age 52.28 ± 11.43 years) or mild (n = 15; age 49.67 ± 7.30 years) disease and compared with age and sex-matched healthy adults (n = 59; age 50.49 ± 10.68 years). We assessed a broad range of immune cell phenotypes to generate a composite score, IMM-AGE, to determine the degree of immune senescence. We found increased immunesenescence features in severe COVID-19 survivors compared to controls including: a reduced frequency and number of naïve CD4 and CD8 T cells (p < 0.0001); increased frequency of EMRA CD4 (p < 0.003) and CD8 T cells (p < 0.001); a higher frequency (p < 0.0001) and absolute numbers (p < 0.001) of CD28−ve CD57+ve senescent CD4 and CD8 T cells; higher frequency (p < 0.003) and absolute numbers (p < 0.02) of PD-1 expressing exhausted CD8 T cells; a two-fold increase in Th17 polarisation (p < 0.0001); higher frequency of memory B cells (p < 0.001) and increased frequency (p < 0.0001) and numbers (p < 0.001) of CD57+ve senescent NK cells. As a result, the IMM-AGE score was significantly higher in severe COVID-19 survivors than in controls (p < 0.001). Few differences were seen for those with moderate disease and none for mild disease. Regression analysis revealed the only pre-existing variable influencing the IMM-AGE score was South Asian ethnicity ( $$beta$$ = 0.174, p = 0.043), with a major influence being disease severity ( $$beta$$ = 0.188, p = 0.01). Our analyses reveal a state of enhanced immune ageing in survivors of severe COVID-19 and suggest this could be related to SARS-Cov-2 infection. Our data support the rationale for trials of anti-immune ageing interventions for improving clinical outcomes in these patients with severe disease.
老年人 COVID-19 严重程度的显著增加是免疫衰老(与年龄有关的免疫系统重塑)的一个明显例子。为了更好地描述康复期免疫衰老与急性疾病严重程度之间的关系,我们测定了 COVID-19 幸存者和非感染对照组的免疫表型。我们对从 103 名 COVID-19 幸存者身上分离的外周血单核细胞进行了详细的免疫表型分析,这些幸存者在康复后 3-5 个月被分为重度(56 人;年龄为 53.12 ± 11.30 岁)、中度(32 人;年龄为 52.28 ± 11.43 岁)或轻度(15 人;年龄为 49.67 ± 7.30 岁),并与年龄和性别匹配的健康成人(59 人;年龄为 50.49 ± 10.68 岁)进行了比较。我们对多种免疫细胞表型进行了评估,得出了一个综合评分 IMM-AGE,以确定免疫衰老的程度。与对照组相比,我们发现严重 COVID-19 幸存者的免疫衰老特征增加,包括:幼稚 CD4 和 CD8 T 细胞的频率和数量减少(p < 0.0001);EMRA CD4(p < 0.003)和 CD8 T 细胞的频率增加(p < 0.001);CD28-ve T 细胞的频率(p < 0.0001)和绝对数量(p < 0.001);CD28-ve CD57+ve 衰老的 CD4 和 CD8 T 细胞的频率更高(p < 0.003),绝对数量更多(p < 0.02);PD-1 表达衰竭的 CD8 T 细胞的频率更高(p < 0.003),绝对数量更多(p < 0.02);Th17 极化增加了两倍(p < 0.0001);记忆 B 细胞的频率更高(p < 0.001),CD57+ve 衰老的 NK 细胞的频率增加(p < 0.0001),数量增加(p < 0.001)。因此,重度 COVID-19 幸存者的 IMM-AGE 评分明显高于对照组(p < 0.001)。中度患者的差异很小,轻度患者则没有差异。回归分析表明,影响 IMM-AGE 评分的唯一先存变量是南亚种族($$beta$$ = 0.174,p = 0.043),主要影响因素是疾病严重程度($$beta$$ = 0.188,p = 0.01)。我们的分析表明,在严重 COVID-19 的幸存者中存在着免疫老化增强的状态,这可能与 SARS-Cov-2 感染有关。我们的数据支持对这些重症患者进行抗免疫老化干预试验以改善临床疗效的理论依据。
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引用次数: 0
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Immunity & Ageing
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