Mechanisms of Ageing and Development最新文献_第9页

Senolytics rejuvenate aging cardiomyopathy in human cardiac organoids 老年性药物使人类心脏类器官老化的心肌病恢复活力。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112007

Mariangela Scalise , Eleonora Cianflone , Claudia Quercia , Loredana Pagano , Antonio Chiefalo , Antonio Stincelli , Annalaura Torella , Barbara Puccio , Gianluca Santamaria , Hiram P. Guzzi , Pierangelo Veltri , Antonella De Angelis , Konrad Urbanek , Georgina M. Ellison-Hughes , Daniele Torella , Fabiola Marino

Background

Human cardiac organoids closely replicate the architecture and function of the human heart, offering a potential accurate platform for studying cellular and molecular features of aging cardiomyopathy. Senolytics have shown potential in addressing age-related pathologies but their potential to reverse aging-related human cardiomyopathy remains largely unexplored.

Methods

We employed human iPSC-derived cardiac organoids (hCOs/hCardioids) to model doxorubicin(DOXO)-induced cardiomyopathy in an aged context. hCardioids were treated with DOXO and subsequently with a combination of two senolytics: dasatinib (D) and quercetin (Q).

Results

DOXO-treated hCardioids exhibited significantly increased oxidative stress, DNA damage (pH2AX), cellular senescence (p16^INK4A) and decreased cell proliferation associated with a senescence-associated secretory phenotype (SASP). DOXO-treated hCardioids were considerably deprived of cardiac progenitors and displayed reduced cardiomyocyte proliferation as well as contractility. These distinctive aging-associated characteristics were confirmed by global RNA-sequencing analysis. Treatment with D+Q reversed these effects, reducing oxidative stress and senescence markers, alleviating SASP, and restoring hCardioids viability and function. Additionally, senolytics replenished cardiac progenitors and reversed the cardiomyocyte proliferation deficit.

Conclusions

Doxorubicin triggers an age-associated phenotype in hCardioids reliably modelling the main cellular and molecular features of aging cardiomyopathy. Senescence is a key mechanism of the aged-hCOs phenotype as senolytics rejuvenated aged-hCardioids restoring their structure and function while reverting the age-associated regenerative deficit.

背景：人类心脏类器官与人类心脏的结构和功能紧密复制，为研究衰老性心肌病的细胞和分子特征提供了一个潜在的准确平台。老年性药物在解决与年龄相关的病理方面显示出潜力，但其逆转与年龄相关的人类心肌病的潜力仍未得到很大程度的探索。方法：我们使用人类ipsc衍生的心脏类器官（hCOs/hCardioids）来模拟阿霉素（DOXO）诱导的老年心肌病。结果：DOXO处理的hCardioids表现出明显的氧化应激、DNA损伤（pH2AX）、细胞衰老（p16INK4A）以及与衰老相关的分泌表型（SASP）相关的细胞增殖降低。doxo处理的类心肌细胞明显缺乏心脏祖细胞，心肌细胞增殖和收缩能力降低。这些独特的衰老相关特征被全球rna测序分析证实。D+Q治疗逆转了这些作用，降低了氧化应激和衰老标志物，缓解了SASP，恢复了类心细胞的活力和功能。此外，老年药补充心脏祖细胞并逆转心肌细胞增殖缺陷。结论：阿霉素在类心脏中触发一种与年龄相关的表型，可靠地模拟了衰老性心肌病的主要细胞和分子特征。衰老是衰老型hcos表型的关键机制，因为抗衰老药物使衰老的类心脏恢复其结构和功能，同时恢复与年龄相关的再生缺陷。

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引用次数: 0

Single-cell analysis of human peripheral blood reveals high immune response activity in successful ageing individuals 人类外周血的单细胞分析揭示了成功衰老个体的高免疫反应活性。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112011

Yu Wang , Yuxing Zhang , Ge Gong , Quanzhong Liu , Liangyu Li , Mingjiong Zhang , Shuping Shen , Ran Wang , Jianqing Wu , Wei Xu

Beneficial remodeling of the immune system in successful ageing individuals (centenarians and supercentenarians) is critical for healthy ageing. However, mechanisms for dynamic regulation of immunity during ageing remain unclear. We use single-cell RNA sequencing (scRNA-seq) as an analytical strategy to study the dynamic regulation of immunity during aging and its molecular mechanisms at the single-cell level. We performed an integrative analysis of 87,215 peripheral blood mononuclear cells, from seven supercentenarians, three centenarians, and four elderly controls, generated by single-cell transcriptomics complemented with fluorescence-activated cell sorting. Animals experiments were also conducted to validate the makers of healthy aging found by our bioinformatic analysis and further explore the dynamic of immune changes during aging process. We found that CD8⁺ effector memory T cells and terminally differentiated B cells were enriched in the longevity group (centenarians and supercentenarians), whereas naïve T cells and Tregs were enriched in elderly controls. CD56^dim NK cells in the longevity group activated Fc-γ receptor signaling. The higher antigen-presenting ability of CD14⁺ monocytes in the longevity group and the CellChat analysis indicated that CD14⁺ monocytes might assist active T and B cells. Here, we revealed the adaptive immune remodeling geromarkers of immunosenescence in centenarians and supercentenarians, which could be considered as biomarkers of healthy aging, and might help sustain immune responses and achieve exceptional longevity.

成功衰老个体（百岁老人和超级百岁老人）免疫系统的有益重塑对健康衰老至关重要。然而，衰老过程中免疫动态调节的机制尚不清楚。我们使用单细胞RNA测序（scRNA-seq）作为分析策略，在单细胞水平上研究衰老过程中免疫的动态调控及其分子机制。我们对来自7名超级百岁老人、3名百岁老人和4名老年对照者的87,215个外周血单个核细胞进行了综合分析，这些细胞是通过单细胞转录组学和荧光激活细胞分选相结合产生的。通过动物实验验证生物信息学分析发现的健康衰老因素，进一步探讨衰老过程中免疫变化的动态。我们发现CD8+效应记忆T细胞和终末分化B细胞在长寿组（百岁老人和超百岁老人）中富集，而naïve T细胞和Tregs在老年对照组中富集。长寿组CD56dim NK细胞激活Fc-γ受体信号。长寿组中CD14+单核细胞更高的抗原呈递能力和CellChat分析表明，CD14+单核细胞可能有助于活跃的T细胞和B细胞。本研究揭示了百岁老人和超百岁老人免疫衰老的适应性免疫重塑标记，这些标记可以被认为是健康衰老的生物标记，可能有助于维持免疫反应并实现超长寿命。

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引用次数: 0

Role of chemokines in aging and age-related diseases 趋化因子在衰老和年龄相关疾病中的作用。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112009

Jitendra Kumar Chaudhary , Ajay Kumar Danga , Anita Kumari , Akshay Bhardwaj , Pramod C. Rath

Chemokines (chemotactic cytokines) play essential roles in developmental process, immune cell trafficking, inflammation, immunity, angiogenesis, cellular homeostasis, aging, neurodegeneration, and tumorigenesis. Chemokines also modulate response to immunotherapy, and consequently influence the therapeutic outcome. The mechanisms underlying these processes are accomplished by interaction of chemokines with their cognate cell surface G protein-coupled receptors (GPCRs) and subsequent cellular signaling pathways. Chemokines play crucial role in influencing aging process and age-related diseases across various tissues and organs, primarily through inflammatory responses (inflammaging), recruitment of macrophages, and orchestrated trafficking of other immune cells. Chemokines are categorized in four distinct groups based on the position and number of the N-terminal cysteine residues; namely, the CC, CXC, CX3C, and (X)C. They mediate inflammatory responses, and thereby considerably impact aging process across multiple organ-systems. Therefore, understanding the underlying mechanisms mediated by chemokines may be of crucial importance in delaying and/or modulating the aging process and preventing age-related diseases. In this review, we highlight recent progress accomplished towards understanding the role of chemokines and their cellular signaling pathways involved in aging and age-relaed diseases of various organs. Moreover, we explore potential therapeutic strategies involving anti-chemokines and chemokine receptor antagonists aimed at reducing aging and mitigating age-related diseases. One of the modern methods in this direction involves use of chemokine receptor antagonists and anti-chemokines, which suppress the pro-inflammatory response, thereby helping in resolution of inflammation. Considering the wide-spectrum of functional involvements of chemokines in aging and associated diseases, several clinical trials are being conducted to develop therapeutic approaches using anti-chemokine and chemokine receptor antagonists to improve life span and promote healthy aging.

趋化因子（趋化因子）在发育过程、免疫细胞运输、炎症、免疫、血管生成、细胞稳态、衰老和肿瘤发生等方面发挥着重要作用。趋化因子也调节对免疫治疗的反应，从而影响治疗结果。这些过程的机制是通过趋化因子与其同源细胞表面G蛋白偶联受体（gpcr）和随后的细胞信号通路的相互作用来完成的。趋化因子在影响各种组织和器官的衰老过程和与年龄相关的疾病中起着至关重要的作用，主要是通过炎症反应（炎症）、巨噬细胞的募集和其他免疫细胞的协调运输。根据n端半胱氨酸残基的位置和数量，趋化因子可分为四组；即CC、CXC、CX3C、(X)C。它们介导炎症反应，从而在很大程度上影响多个器官系统的衰老过程。因此，了解趋化因子介导的潜在机制可能对延缓和/或调节衰老过程和预防与年龄相关的疾病至关重要。在这篇综述中，我们重点介绍了在了解趋化因子及其细胞信号通路在衰老和各器官年龄相关疾病中的作用方面取得的最新进展。此外，我们探索潜在的治疗策略，包括趋化因子和趋化因子受体拮抗剂，旨在减少衰老和减轻与年龄相关的疾病。这方面的现代方法之一涉及使用趋化因子受体拮抗剂和抗趋化因子，它们抑制促炎反应，从而帮助解决炎症。考虑到趋化因子在衰老和相关疾病中的广泛功能参与，一些临床试验正在进行，以开发使用趋化因子受体拮抗剂的治疗方法，以延长寿命并促进健康衰老。

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引用次数: 0

Aberrant expression of messenger and small noncoding RNAomes in aged skin of rats 衰老大鼠皮肤中信使和小非编码rna的异常表达。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112022

Danyang Zhao , Yu Wang , Chuandong Wang , Yaxin Xue , Hao Lv , Wei Xu , Dong Han , Yu Sun , Qingfeng Li

The exact mechanisms and key functional molecules involved in skin ageing remain largely unknown. Studies linking the expression of messenger RNAs (mRNAs) and small noncoding RNAs (sncRNAs) to skin ageing are limited. In this study, we performed RNA sequencing to assess the effects of ageing on the expression of mRNAs and sncRNAs in rat skin. Our results revealed that 241 mRNAs, 109 microRNAs (miRNAs), 20 piwi-interacting RNAs (piRNAs), 45 small nucleolar RNAs (snoRNAs), and 7 small nuclear RNAs (snRNAs) were significantly differentially expressed in the skin of aged rats compared to their younger counterparts. Histological validation using RT-qPCR further verified the significant differential expression of 13 mRNAs, 7 miRNAs, 2 piRNAs, 15 snoRNAs, and 1 snRNA. Additionally, several sncRNAs showed differential expression across various tissues, suggesting that they may have broad correlations with ageing. After establishing cellular senescence in skin fibroblasts, we identified 4 mRNAs, 4 miRNAs, and 10 snoRNAs that may mediate skin ageing by modulating fibroblast senescence. Notably, overexpression or knockdown of some differentially expressed RNAs in fibroblasts influenced cellular senescence, indicating that these RNAs could play an important role in the skin ageing process. These findings highlight their potential significance for future treatments of age-related skin disorders.

皮肤老化的确切机制和关键功能分子在很大程度上仍然未知。将信使rna （mrna）和小非编码rna （sncRNAs）的表达与皮肤老化联系起来的研究是有限的。在这项研究中，我们进行了RNA测序，以评估衰老对大鼠皮肤mrna和sncRNAs表达的影响。我们的研究结果显示，与年轻大鼠相比，老年大鼠皮肤中有241种mrna、109种microRNAs （miRNAs）、20种piwi相互作用rna （piRNAs）、45种小核核rna （snoRNAs）和7种小核rna （snrna）的表达存在显著差异。RT-qPCR进一步验证了13个mrna、7个mirna、2个pirna、15个snorna和1个snRNA的显著差异表达。此外，一些sncrna在不同组织中表现出差异表达，这表明它们可能与衰老有广泛的相关性。在皮肤成纤维细胞中建立细胞衰老后，我们鉴定了4种mrna、4种mirna和10种snorna，它们可能通过调节成纤维细胞衰老来介导皮肤衰老。值得注意的是，成纤维细胞中一些差异表达rna的过表达或敲低会影响细胞衰老，这表明这些rna可能在皮肤衰老过程中发挥重要作用。这些发现强调了它们对未来治疗与年龄有关的皮肤疾病的潜在意义。

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引用次数: 0

Molecular mechanisms and potential interventions during aging-associated sarcopenia 衰老相关肌肉减少症的分子机制和潜在干预措施。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112020

Xiaoqin Luo , Jin Wang , Qingqing Ju , Tianyu Li , Xiuli Bi

Sarcopenia, a common condition observed in the elderly, presenting a significant public health challenge due to its high prevalence, insidious onset and diverse systemic effects. Despite ongoing research, the precise etiology of sarcopenia remains elusive. Aging-related processes, which included inflammation, oxidative stress, compromised mitochondrial function and apoptosis, have been implicated in its development. Notably, effective pharmacological treatments for sarcopenia are currently lacking, highlighting the necessity for a deeper understanding of its pathogenesis and causative factors to enable proactive interventions. This article is aimed to provide an extensive overview of the pathogenesis of sarcopenia, along with a summary of current treatment and prevention strategies.

肌肉疏松症是一种常见于老年人的疾病，由于其发病率高、起病隐匿和对全身产生多种影响，给公共卫生带来了重大挑战。尽管研究仍在进行，但肌肉疏松症的确切病因仍难以捉摸。与衰老相关的过程，包括炎症、氧化应激、线粒体功能受损和细胞凋亡，都与肌少症的发生有关。值得注意的是，目前还缺乏治疗肌肉疏松症的有效药物，因此有必要深入了解其发病机制和致病因素，以便采取积极干预措施。本文旨在广泛概述肌肉疏松症的发病机制，并总结当前的治疗和预防策略。

引用次数: 0

The telomere connection between aging and cancer: The burden of replication stress and dysfunction 衰老和癌症之间的端粒关系：复制压力和功能障碍的负担。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2025.112026

Virginia Boccardi , Luigi Marano

Aging is a complex process that affects individuals at the molecular, cellular, tissue, and systemic levels, arising from the cumulative effects of damage and reduced repair mechanisms. This process leads to the onset of age-related diseases, including cancer, which exhibits increased incidence with age. Telomeres, the protective caps at chromosome ends, play a crucial role in genome stability and are closely connected with aging and age-related disorders. Both excessively short and long telomere lengths may contribute to cancer development when their balance is disrupted. Fragile telomeres, characterized by abnormalities and replication stress, may provide novel insights into the connection between aging and cancer. The accumulation of fragile telomeres, possibly due to intense replicative stress, may represent a key factor. Given the dynamic nature of telomeres, large longitudinal studies are essential for understanding their role in aging and cancer susceptibility, which is crucial for developing effective strategies to promote healthy aging and mitigate cancer risk.

衰老是一个复杂的过程，它在分子、细胞、组织和系统水平上影响个体，是由损伤和修复机制减弱的累积效应引起的。这一过程导致与年龄有关的疾病，包括癌症的发病，其发病率随着年龄的增长而增加。端粒是染色体末端的保护帽，在基因组稳定中起着至关重要的作用，并与衰老和年龄相关疾病密切相关。当端粒长度的平衡被破坏时，过短和过长都可能导致癌症的发展。脆弱的端粒，以异常和复制压力为特征，可能为衰老和癌症之间的联系提供新的见解。脆弱端粒的积累，可能是由于强烈的复制压力，可能是一个关键因素。考虑到端粒的动态特性，大型纵向研究对于了解它们在衰老和癌症易感性中的作用至关重要，这对于制定促进健康衰老和降低癌症风险的有效策略至关重要。

引用次数: 0

Protective effects and bioinformatic analysis of narciclasine on vascular aging via cross-talk between inflammation and metabolism through inhibiting skeletal muscle-specific ceramide synthase 1 水仙素通过抑制骨骼肌特异性神经酰胺合成酶1在炎症与代谢间的交互作用对血管衰老的保护作用及生物信息学分析

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-02-01 DOI: 10.1016/j.mad.2024.112021

Zhiyi Fang , Linghuan Wang , Yabin Wang , Yan Ma , Yan Fang , Weiwei Zhang , Ruihua Cao , Yingjie Zhang , Hui Li , Sijia Chen , Lei Tian , Xiaoying Shen , Feng Cao

Objective

The senescence of smooth muscle is one of the independent risk factors in atherosclerosis progression in which the vascular inflammation plays an important role on vascular dysfunction. This study is designed to explore the novel vascular aging biomarkers and screen the potential molecular interventional targets through bioinformatic analysis.

Results

Transcriptional analysis was conducted based on the GSE16487 open access database, which included 15 human vascular tissue samples from two groups: young group (≤ 60 years old, n = 8) and aged group (≥ 75 years old, n = 7). There were 275 differential expression genes (119 upregulated and 156 downregulated genes) with minimum 1.5-fold change between two groups. 9 genes were mainly participated in inflammation-related signaling pathways, in which narciclasine was validated as the most effective candidate for modulation the ceramide synthesis. In vitro and animal study demonstrated that narciclasine reversed vascular aging by inhibiting skeletal muscle-specific ceramide synthase 1 (CerS1), reducing the ceramide level derived from CerS1, and improving fat deposition and circulating glycolipid metabolism.

Conclusion

Narciclasine attenuates vascular aging and modulates the cross-talk between inflammation and metabolism via inhibiting skeletal muscle-specific ceramide synthase 1.

目的：平滑肌衰老是动脉粥样硬化进展的独立危险因素之一，其中血管炎症在血管功能障碍中起重要作用。本研究旨在通过生物信息学分析，探索新的血管老化生物标志物，筛选潜在的分子干预靶点。结果：基于GSE16487开放获取数据库进行转录分析，共纳入青年组（≤60岁，n = 8）和老年组（≥75岁，n = 7）两组15份人血管组织样本，差异表达基因275个（上调119个，下调156个），两组差异表达基因差异最小1.5倍。9个基因主要参与炎症相关的信号通路，其中水仙素被证实是调节神经酰胺合成最有效的候选基因。体外和动物实验表明，水仙素通过抑制骨骼肌特异性神经酰胺合成酶1 （CerS1）、降低CerS1衍生的神经酰胺水平、改善脂肪沉积和循环糖脂代谢来逆转血管衰老。结论：水仙素通过抑制骨骼肌特异性神经酰胺合酶1，减缓血管衰老，调节炎症与代谢的交互作用。

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引用次数: 0

IRF1-RIG-I signaling defects in the aged alveolar epithelial cells may contribute to decreased pulmonary antiviral immune responses 衰老肺泡上皮细胞中的IRF1-RIG-I信号缺陷可能导致肺部抗病毒免疫反应下降。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-01-26 DOI: 10.1016/j.mad.2025.112037

Shan Li , Qianqian Lu , Jiao Lu , Xiaotong Song , Yang Gu , Xuefeng Duan , Wei Jiang , Guanglei Gu , Mengli Zheng , Lixin Xie , Min Fang

Background

Alveolar epithelial cells (AECs) are the primary targets of many pathogens and play an important role in sensing viruses and regulating immunity. Yet, little is known about the antiviral responses in the aged AECs.

Methods

The responses of young or aged AECs after viral infection were analyzed using methods such as flow cytometry, quantitative real-time PCR, Western blot detection, and transwell chemotaxis assay. Deep sequencing and KEGG analysis were used to identify key pathways and genes associated with aged AECs, followed by functional analysis.

Results

The retinoic acid-inducible gene I (RIG-I) signaling is defective in aged AECs after influenza A virus (IAV) infection. The interferon regulatory factor 1 (IRF1) binds the promoter of RIG-I gene Ddx58 to activate its expression. The regulation of IRF1 is also defective in AECs from aged mice. Fewer NK cells, monocytes, and T cells are recruited by the cell supernatant from PR8-infected aged AECs. Importantly, IRF1-RIG-I signaling is also impaired in the AECs of elderly people after IAV infection.

Conclusion

Ageing impairs IRF1-RIG-I signaling in AECs, and the defective responses in AECs may contribute to reduced immune cell recruitment and activation in aged individuals after pulmonary viral infection.

背景：肺泡上皮细胞（AECs）是许多病原体的主要靶点，在病毒感知和免疫调节中起着重要作用。然而，对老年aec的抗病毒反应知之甚少。方法：采用流式细胞术、实时荧光定量PCR、Western blot检测、transwell趋化试验等方法分析年轻、老年AECs感染病毒后的反应。采用深度测序和KEGG分析确定与老年AECs相关的关键通路和基因，然后进行功能分析。结果：甲型流感病毒（IAV）感染老年aec后，视黄酸诱导基因I （RIG-I）信号通路存在缺陷。干扰素调节因子1 （IRF1）结合RIG-I基因Ddx58的启动子激活其表达。IRF1的调控在老年小鼠aec中也存在缺陷。pr8感染的老年aec细胞上清中募集的NK细胞、单核细胞和T细胞较少。重要的是，IRF1-RIG-I信号在IAV感染后的老年人aec中也受到损害。结论：衰老损害了AECs中irf1 - rig - 1信号通路，AECs应答缺陷可能导致肺部病毒感染后老年人免疫细胞募集和激活减少。

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引用次数: 0

Mangiferin protects mesenchymal stem cells against DNA damage and cellular aging via SIRT1 activation 芒果苷通过激活SIRT1保护间充质干细胞免受DNA损伤和细胞衰老。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-01-26 DOI: 10.1016/j.mad.2025.112038

Gyeong Min Lim , Gwang-Won Cho

The protective effects of mangiferin (MAG) against etoposide- and high glucose (HG)–induced DNA damage and aging were investigated in human bone marrow-mesenchymal stem cells (hBM-MSCs). Etoposide, a topoisomerase II inhibitor, was used to induce double-strand breaks (DSBs) in hBM-MSCs, resulting in increased genotoxicity, elevated levels of the DNA damage sensor ATM and CDKN1A, and decreased levels of the aging markers H3 and H4. MAG activated AMPK and SIRT1, thus protecting against DSB-induced damage. Following long-term exposure to HG, MAG significantly mitigated DNA damage and delayed cellular aging, as evidenced by the preservation of H3, H4, LMNB1, and SIRT1 mRNA levels and reduction in γ-H2AX foci and DSBs. Furthermore, MAG improved genome stability, as indicated by decreased LINE1 expression and increased levels of the heterochromatin marker TRIM28, thereby maintaining H3K9me3 levels. MAG and metformin treatment enhanced cell proliferation, reduced senescence-associated β-galactosidase staining, and lowered the levels of the senescence-associated secretory phenotype factors IL-1A, IL-1B, IL-6, IL-8, CCL2, and CCL20 and senescence marker CDKN1A, CDKN2A and p53. MAG may reduce DNA damage and delay aging in hBM-MSCs under HG conditions, highlighting their potential as therapeutic agents for aging-related diseases.

研究了芒果苷（MAG）对人骨骨髓间充质干细胞（hBM-MSCs） DNA损伤和衰老的保护作用。依托oposide是一种拓扑异构酶II抑制剂，用于诱导hBM-MSCs中的双链断裂（DSBs），导致遗传毒性增加，DNA损伤传感器ATM和CDKN1A水平升高，衰老标志物H3和H4水平降低。MAG激活AMPK和SIRT1，从而防止dsb引起的损伤。长期暴露于HG后，MAG显著减轻了DNA损伤并延缓了细胞衰老，这可以通过保存H3、H4、LMNB1和SIRT1 mRNA水平以及减少γ-H2AX灶和dsb来证明。此外，MAG提高了基因组的稳定性，如LINE1表达降低和异染色质标记TRIM28水平升高所表明的，从而维持了H3K9me3水平。MAG和二甲双胍处理增强细胞增殖，降低衰老相关β-半乳糖苷酶染色，降低衰老相关分泌表型因子IL-1A、IL-1B、IL-6、IL-8、CCL2和CCL20以及衰老标志物CDKN1A、CDKN2A和p53的水平。MAG可能减少HG条件下hBM-MSCs的DNA损伤和延缓衰老，突出其作为衰老相关疾病治疗剂的潜力。

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引用次数: 0

Deciphering the role of cytokines in aging: Biomarker potential and effective targeting 解读细胞因子在衰老中的作用：生物标志物潜力和有效靶向。

IF 5.3 3区医学 Q2 CELL BIOLOGY

Mechanisms of Ageing and Development

Pub Date : 2025-01-18 DOI: 10.1016/j.mad.2025.112036

Panagiotis Poulios, Stamoulis Skampouras, Christina Piperi

Aging is often characterized by chronic inflammation, immune system dysregulation, and cellular senescence with chronically elevated levels of pro-inflammatory cytokines. These small glycoproteins are mainly secreted by immune cells, mediating intercellular communication and immune system modulation through inflammatory signaling. Their pro- and anti-inflammatory effects make them a noteworthy research topic as well as a promising ally in combating inflammation and the aging process. Cytokines exert a synergistic role in aging and disease and may prove useful biomarkers of tissue-specific dysregulation, disease diagnosis and monitoring, presenting potential therapeutic options as anti-inflammatory and senolytic medications. In this review, we address the cellular and molecular mechanisms implicating cytokines in the aging process and related diseases, highlighting their biomarker potential. We focus on the current therapeutic strategies, including specific pharmaceutical agents, supplements, a balanced diet, and healthy habits such as exercise, stress management, and caloric restriction.

衰老通常以慢性炎症、免疫系统失调和细胞衰老为特征，并伴有促炎细胞因子水平的长期升高。这些小糖蛋白主要由免疫细胞分泌，通过炎症信号介导细胞间通讯和免疫系统调节。它们的促炎和抗炎作用使其成为一个值得关注的研究课题，也是对抗炎症和衰老过程的有希望的盟友。细胞因子在衰老和疾病中发挥协同作用，可能被证明是组织特异性失调、疾病诊断和监测的有用生物标志物，作为抗炎和抗衰老药物提供潜在的治疗选择。在这篇综述中，我们讨论了细胞因子在衰老过程和相关疾病中的细胞和分子机制，并强调了它们的生物标志物潜力。我们关注当前的治疗策略，包括特定的药物，补充剂，均衡的饮食和健康的习惯，如运动，压力管理和热量限制。

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引用次数: 0