Pub Date : 2025-02-01DOI: 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.
{"title":"Molecular mechanisms and potential interventions during aging-associated sarcopenia","authors":"Xiaoqin Luo , Jin Wang , Qingqing Ju , Tianyu Li , Xiuli Bi","doi":"10.1016/j.mad.2024.112020","DOIUrl":"10.1016/j.mad.2024.112020","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112020"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142818579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 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.
{"title":"The telomere connection between aging and cancer: The burden of replication stress and dysfunction","authors":"Virginia Boccardi , Luigi Marano","doi":"10.1016/j.mad.2025.112026","DOIUrl":"10.1016/j.mad.2025.112026","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112026"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142979055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 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.
{"title":"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","authors":"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","doi":"10.1016/j.mad.2024.112021","DOIUrl":"10.1016/j.mad.2024.112021","url":null,"abstract":"<div><h3>Objective</h3><div>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.</div></div><div><h3>Results</h3><div>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, <em>n</em> = 8) and aged group (≥ 75 years old, <em>n</em> = 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. <em>In vitro</em> 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.</div></div><div><h3>Conclusion</h3><div>Narciclasine attenuates vascular aging and modulates the cross-talk between inflammation and metabolism via inhibiting skeletal muscle-specific ceramide synthase 1.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"223 ","pages":"Article 112021"},"PeriodicalIF":5.3,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142872476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-26DOI: 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.
{"title":"IRF1-RIG-I signaling defects in the aged alveolar epithelial cells may contribute to decreased pulmonary antiviral immune responses","authors":"Shan Li , Qianqian Lu , Jiao Lu , Xiaotong Song , Yang Gu , Xuefeng Duan , Wei Jiang , Guanglei Gu , Mengli Zheng , Lixin Xie , Min Fang","doi":"10.1016/j.mad.2025.112037","DOIUrl":"10.1016/j.mad.2025.112037","url":null,"abstract":"<div><h3>Background</h3><div>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.</div></div><div><h3>Methods</h3><div>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.</div></div><div><h3>Results</h3><div>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 <em>Ddx58</em> 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.</div></div><div><h3>Conclusion</h3><div>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.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112037"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-26DOI: 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.
{"title":"Mangiferin protects mesenchymal stem cells against DNA damage and cellular aging via SIRT1 activation","authors":"Gyeong Min Lim , Gwang-Won Cho","doi":"10.1016/j.mad.2025.112038","DOIUrl":"10.1016/j.mad.2025.112038","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112038"},"PeriodicalIF":5.3,"publicationDate":"2025-01-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143059729","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-18DOI: 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.
{"title":"Deciphering the role of cytokines in aging: Biomarker potential and effective targeting","authors":"Panagiotis Poulios, Stamoulis Skampouras, Christina Piperi","doi":"10.1016/j.mad.2025.112036","DOIUrl":"10.1016/j.mad.2025.112036","url":null,"abstract":"<div><div>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.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112036"},"PeriodicalIF":5.3,"publicationDate":"2025-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008064","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-17DOI: 10.1016/j.mad.2025.112027
Judith Félix, Estefanía Díaz-Del Cerro, Antonio Garrido, Mónica De la Fuente
{"title":"Corrigendum to \"Characterization of a natural model of adult mice with different rate of aging\" [Mech. Ageing Dev. 222 (2024), 111991].","authors":"Judith Félix, Estefanía Díaz-Del Cerro, Antonio Garrido, Mónica De la Fuente","doi":"10.1016/j.mad.2025.112027","DOIUrl":"https://doi.org/10.1016/j.mad.2025.112027","url":null,"abstract":"","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":" ","pages":"112027"},"PeriodicalIF":5.3,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008085","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Torque Teno Virus (TTV), an "orphan" virus with unclear pathology, has been associated with various diseases and immune dysfunctions. This study investigates the link between TTV viremia and clinical markers in patients with severe to very severe COPD undergoing respiratory rehabilitation.
Methods
We analyzed 102 elderly COPD patients, stratified by TTV viremia levels (< or ≥ 4 log10 copies/mL). Clinical markers—including mortality, inflammatory-oxidative parameters (Lymphocyte/Monocyte, Neutrophil/Lymphocyte, and Platelet/Lymphocyte ratios), IL-6 (measured via ELISA assay), and DNA damage (assessed via comet assay)—were evaluated.
Results
Of the patients, 62.75 % had TTV viremia levels > 4 log10 copies/mL. No associations were found between TTV levels and sex or obesity. However, higher TTV viremia correlated with increased DNA damage and significantly lower 5-year survival probability.
Conclusion
Patients with TTV levels ≥ 4 log10 copies/mL exhibited the lowest survival probability, though DNA damage emerged as a stronger determinant of outcomes. This study raises key scientific questions on the role of TTV in COPD. Specifically, it explores whether TTV may serve as a potential marker for poor prognosis in COPD and whether rehabilitation strategies for these patients could be customized based on DNA damage and/or viremia.
{"title":"The effect of torque teno virus (TTV) infection on clinical outcomes, genomic integrity, and mortality in COPD patients","authors":"Patrizia Russo , Francesca Milani , Dolores Limongi , Carla Prezioso , Federica Novazzi , Francesca Drago Ferrante , Fabrizio Maggi , Guido Antonelli , Stefano Bonassi","doi":"10.1016/j.mad.2024.112024","DOIUrl":"10.1016/j.mad.2024.112024","url":null,"abstract":"<div><h3>Introduction</h3><div>Torque Teno Virus (TTV), an \"orphan\" virus with unclear pathology, has been associated with various diseases and immune dysfunctions. This study investigates the link between TTV viremia and clinical markers in patients with severe to very severe COPD undergoing respiratory rehabilitation.</div></div><div><h3>Methods</h3><div>We analyzed 102 elderly COPD patients, stratified by TTV viremia levels (< or ≥ 4 log10 copies/mL). Clinical markers—including mortality, inflammatory-oxidative parameters (Lymphocyte/Monocyte, Neutrophil/Lymphocyte, and Platelet/Lymphocyte ratios), IL-6 (measured via ELISA assay), and DNA damage (assessed via comet assay)—were evaluated.</div></div><div><h3>Results</h3><div>Of the patients, 62.75 % had TTV viremia levels > 4 log<sub>10</sub> copies/mL. No associations were found between TTV levels and sex or obesity. However, higher TTV viremia correlated with increased DNA damage and significantly lower 5-year survival probability.</div></div><div><h3>Conclusion</h3><div>Patients with TTV levels ≥ 4 log<sub>10</sub> copies/mL exhibited the lowest survival probability, though DNA damage emerged as a stronger determinant of outcomes. This study raises key scientific questions on the role of TTV in COPD. Specifically, it explores whether TTV may serve as a potential marker for poor prognosis in COPD and whether rehabilitation strategies for these patients could be customized based on DNA damage and/or viremia.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112024"},"PeriodicalIF":5.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008067","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-14DOI: 10.1016/j.mad.2025.112028
Ivana Lansweers , Sharon van Rijthoven , Jack J.W.A. van Loon
The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex plays a crucial role in connecting the nuclear envelope to the cytoskeleton, providing structural support to the nucleus and facilitating mechanical signaling between the extracellular environment and the nucleus. Research in mechanobiology onboard the International Space Station (ISS) and in simulated microgravity (SMG) highlight the importance of gravity in functional mechanotransduction. Although the altered gravity research regarding mechanobiology has been greatly focused on the cytoskeleton and the extracellular matrix (ECM), recent research demonstrates that SMG also induces changes in nuclear mechanics and gene expression patterns, which have been shown to be LINC complex dependent. Additionally, dysregulation of the LINC complex disrupts nuclear integrity which leads to nuclear shape abnormalities in both Hutchinson-Gilford Progeria Syndrome (HGPS) and aged cells, which highlights the significance of the LINC complex and related proteins in ageing and age-related disorders. Interestingly, as the effects of spaceflight closely resemble those found in the elderly, the microgravity environment seems to induce an accelerated ageing phenotype in astronauts. Therefore, this review will explore the role of the LINC complex and related proteins in ageing and in microgravity, to further elucidate the interplay between loss of gravitational loading and ageing.
核骨架与细胞骨架连接物（Linker of Nucleoskeleton and Cytoskeleton， LINC）复合物在连接核包膜与细胞骨架、为细胞核提供结构支持以及促进细胞外环境与细胞核之间的机械信号传导方面起着至关重要的作用。国际空间站（ISS）和模拟微重力（SMG）上的力学生物学研究强调了重力在功能机械转导中的重要性。虽然关于力学生物学的重力改变研究主要集中在细胞骨架和细胞外基质（ECM）上，但最近的研究表明，SMG也会诱导核力学和基因表达模式的变化，这些变化已被证明是LINC复合物依赖的。此外，LINC复合物的失调破坏了核完整性，导致Hutchinson-Gilford早衰综合征（HGPS）和衰老细胞的核形状异常，这突出了LINC复合物和相关蛋白在衰老和年龄相关疾病中的重要性。有趣的是，由于太空飞行的影响与老年人的影响非常相似，微重力环境似乎会导致宇航员加速衰老。因此，本文将探讨LINC复合物及其相关蛋白在衰老和微重力环境中的作用，以进一步阐明重力负荷丧失与衰老之间的相互作用。
{"title":"The role of the LINC complex in ageing and microgravity","authors":"Ivana Lansweers , Sharon van Rijthoven , Jack J.W.A. van Loon","doi":"10.1016/j.mad.2025.112028","DOIUrl":"10.1016/j.mad.2025.112028","url":null,"abstract":"<div><div>The Linker of Nucleoskeleton and Cytoskeleton (LINC) complex plays a crucial role in connecting the nuclear envelope to the cytoskeleton, providing structural support to the nucleus and facilitating mechanical signaling between the extracellular environment and the nucleus. Research in mechanobiology onboard the International Space Station (ISS) and in simulated microgravity (SMG) highlight the importance of gravity in functional mechanotransduction. Although the altered gravity research regarding mechanobiology has been greatly focused on the cytoskeleton and the extracellular matrix (ECM), recent research demonstrates that SMG also induces changes in nuclear mechanics and gene expression patterns, which have been shown to be LINC complex dependent. Additionally, dysregulation of the LINC complex disrupts nuclear integrity which leads to nuclear shape abnormalities in both Hutchinson-Gilford Progeria Syndrome (HGPS) and aged cells, which highlights the significance of the LINC complex and related proteins in ageing and age-related disorders. Interestingly, as the effects of spaceflight closely resemble those found in the elderly, the microgravity environment seems to induce an accelerated ageing phenotype in astronauts. Therefore, this review will explore the role of the LINC complex and related proteins in ageing and in microgravity, to further elucidate the interplay between loss of gravitational loading and ageing.</div></div>","PeriodicalId":18340,"journal":{"name":"Mechanisms of Ageing and Development","volume":"224 ","pages":"Article 112028"},"PeriodicalIF":5.3,"publicationDate":"2025-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143008069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-11DOI: 10.1016/j.mad.2025.112025
Robert J. Pignolo , Abhishek Chandra
Preclinical models of age-related osteoporosis have been developed based on the accumulation and clearance of senescent cells. The former include animal models based on telomere dysfunction and focal radiation; the latter based on genetic and pharmacological targeting (i.e., removal) of senescent cells. The weight of evidence using these models suggests that cellular senescence plays a key role in the pathophysiology of aging-onset bone loss with the senescence-associated secretory phenotype (SASP) mediating local and systemic deleterious effects on the skeleton. Mitochondrial dysfunction has also been implicated in senescence and age-related comorbidities, including osteoporosis, and knock-in mutations in the mtDNA polymerase gamma (Polg) gene in mice may recapitulate similar respiratory chain complex defects in aged individual with osteoporosis. This and other contributions to senile osteoporosis may also be identified by the careful evaluation of non-genetic paradigms of human accelerated aging. Premature aging syndromes, especially those with a prominent bone loss phenotype, include clinical scenarios of skeletal unloading, premature ovarian failure and survival from childhood cancers. These non-hereditary progeroid syndromes implicate the involvement of lineage switching to an adipogenic fate, inhibition of Wnt signaling, increased osteoclastogenesis and activation frequency of osteoclasts, as well as the substantial burden of senescent cell accumulation.
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