Aging Cell最新文献

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Epigenetic modulation rescues neurodevelopmental deficits in Syngap1+/− mice
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-29 DOI: 10.1111/acel.14408
Akash Kumar Singh, Ila Joshi, Neeharika M. N. Reddy, Sushmitha S. Purushotham, M. Eswaramoorthy, Madavan Vasudevan, Sourav Banerjee, James P. Clement, Tapas K. Kundu
{"title":"Epigenetic modulation rescues neurodevelopmental deficits in Syngap1+/− mice","authors":"Akash Kumar Singh,&nbsp;Ila Joshi,&nbsp;Neeharika M. N. Reddy,&nbsp;Sushmitha S. Purushotham,&nbsp;M. Eswaramoorthy,&nbsp;Madavan Vasudevan,&nbsp;Sourav Banerjee,&nbsp;James P. Clement,&nbsp;Tapas K. Kundu","doi":"10.1111/acel.14408","DOIUrl":"10.1111/acel.14408","url":null,"abstract":"<p>SYNGAP1 is a Ras GTPase-activating protein that plays a crucial role during brain development and in synaptic plasticity. Sporadic heterozygous mutations in <i>SYNGAP1</i> affect social and emotional behaviour observed in intellectual disability (ID) and autism spectrum disorder (ASD). Although neurophysiological deficits have been extensively studied, the epigenetic landscape of <i>SYNGAP1</i> mutation-mediated intellectual disability is unexplored. Here, we have found that the p300/CBP specific acetylation marks of histones are significantly repressed in the hippocampus of adolescent <i>Syngap1</i><sup><i>+/−</i></sup> mice. Additionally, we observed decreased dendritic branching of newly born DCX<sup>+</sup> neurons in these mice, suggesting altered adult hippocampal neurogenesis. To establish the causal relationship of <i>Syngap1</i><sup><i>+/−</i></sup> phenotype and the altered histone acetylation signature we have treated 2–4 months old <i>Syngap1</i><sup><i>+/−</i></sup> mice with glucose-derived carbon nanosphere (CSP) conjugated potent small molecule activator (TTK21) of p300/CBP lysine acetyltransferase (CSP-TTK21). The enhancement of the p300/CBP specific acetylation marks of histones by CSP-TTK21 restored synaptic functions, increased dendritic branching of DCX<sup>+</sup> neurons, enables the capability to reorganise cortical circuits in response to change in the sensory stimuli, and improves behavioural measures in <i>Syngap1</i><sup><i>+/−</i></sup> mice that are very closely comparable to wild type littermates. Further, hippocampal RNA-Seq analysis of these mice revealed that the expression of many critical genes such as Adcy1, Ntrk3, Egr1, and Foxj1 which are key regulators of synaptic plasticity and neurogenesis and are well associated with ID/ASD reversed upon CSP-TTK21 treatment. This study could be the first demonstration of the reversal of autistic behaviour and neural wiring upon the modulation of altered epigenetic modification(s).</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14408","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Raman Spectroscopy in Cellular and Tissue Aging Research
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-28 DOI: 10.1111/acel.14494
Jeong Hee Kim, Daejong Yang, Seungman Park
{"title":"Raman Spectroscopy in Cellular and Tissue Aging Research","authors":"Jeong Hee Kim,&nbsp;Daejong Yang,&nbsp;Seungman Park","doi":"10.1111/acel.14494","DOIUrl":"10.1111/acel.14494","url":null,"abstract":"<p>The establishment of various molecular, physiological, and genetic markers for cellular senescence and aging-associated conditions has progressed the aging study. To identify such markers, a combination of optical, proteomic-, and sequencing-based tools is primarily used, often accompanying extrinsic labels. Yet, the tools for clinical detection at the molecular, cellular, and tissue levels are still lacking which profoundly hinders advancements in the specific detection and timely prevention of aging-related diseases and pathologies. Raman spectroscopy, with its capability for rapid, label-free, and non-invasive analysis of molecular compositions and alterations in aging cells and tissues, holds considerable promise for in vivo applications. In this review, we present recent advancements in the application of Raman spectroscopy to the study of aging in cells and tissues. We explore the use of Raman spectroscopy and related techniques for detecting cellular aging and senescence, focusing on the molecular alterations that accompany these processes. Subsequently, we provide a review of the application of Raman spectroscopy in identifying aging-related changes in various molecules within tissues and organs.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14494","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143057565","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Correction to “Rutin is a Potent Senomorphic Agent to Target Senescent Cells and Can Improve Chemotherapeutic Efficacy” 更正“芦丁是一种针对衰老细胞的强效Senomorphic Agent,可以提高化疗疗效”。
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-17 DOI: 10.1111/acel.14488
{"title":"Correction to “Rutin is a Potent Senomorphic Agent to Target Senescent Cells and Can Improve Chemotherapeutic Efficacy”","authors":"","doi":"10.1111/acel.14488","DOIUrl":"10.1111/acel.14488","url":null,"abstract":"<p>Liu, H., Xu, Q., Wufuer, H., Li, Z., Sun, R., Jiang, Z., Dou, X., Fu, Q., Campisi, J., Sun, Y. (2024). Rutin is a potent senomorphic agent to target senescent cells and can improve chemotherapeutic efficacy. <i>Aging Cell</i> 23(1): e13921.</p><p>In Figure 5e, for SA-β-Gal staining of mouse tissues, the Placebo image was mistakenly picked up to make the original panel. The corrected figure is provided below.</p><p>We apologize for this error.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14488","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142996357","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Higher Intron Retention Levels in Female Alzheimer's Brains May Be Linked to Disease Prevalence 女性阿尔茨海默氏症患者大脑中较高的内含子保留水平可能与疾病患病率有关。
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-13 DOI: 10.1111/acel.14457
Ching-Thong Choo, Chao-Yong Leow, Chin-Tong Ong
{"title":"Higher Intron Retention Levels in Female Alzheimer's Brains May Be Linked to Disease Prevalence","authors":"Ching-Thong Choo,&nbsp;Chao-Yong Leow,&nbsp;Chin-Tong Ong","doi":"10.1111/acel.14457","DOIUrl":"10.1111/acel.14457","url":null,"abstract":"<p>Multimodal study of Alzheimer's disease (AD) dorsolateral prefrontal cortex (DLPFC) showed AD-related aberrant intron retention (IR) and proteomic changes not observed at the RNA level. However, the role of sex and how IR may impact the proteome are unclear. Analysis of DLPFC transcriptome showed a clear sex-biased pattern where female AD had 1645 elevated IR events compared to 80 in male AD DLPFC. Increased IR is correlated with lower mRNA levels, suggestive of nonsense-mediated mRNA decay. Two hundred thirty-three mRNAs with elevated IR in females were curated AD genes enriched for ubiquitin-like protein ligase and Tau protein binding. Increased IR genes in combined sex and female AD cohorts showed significant changes in their protein expression patterns with 11%–24% of them differential expressed proteins (DEP), alluding to the regulation of AD proteome by IR independent of RNA level. Upregulated DEPs in male AD were linked to RNA splicing that may prevent aberrant IR, whereas in female AD, they overlapped significantly more with the MAPK/metabolism module associated with cognitive decline. IR genes appeared to be significantly downregulated in specific female AD inhibitory and excitatory neurons compared to control. Differentially retained introns in female AD have elevated H3K27ac marks, strong CTCF binding at their flanking exons, and enriched for PABPC1 motif. Given that H3K27ac is repressive over gene bodies in aged brain and CTCF impedes transcription elongation, their binding patterns can delay co-transcriptional recruitment of spliceosome to cause IR, which may in turn contribute to different trajectories of AD pathology in women.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142976831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Additional Cover
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14479
Todd W. Dowrey, Samuel F. Cranston, Nicholas Skvir, Yvonne Lok, Brian Gould, Bradley Petrowitz, Daniel Villar, Jidong Shan, Marianne James, Mark Dodge, Anna C. Belkina, Richard M. Giadone, Sofiya Milman, Paola Sebastiani, Thomas T. Perls, Stacy L. Andersen, George J. Murphy
{"title":"Additional Cover","authors":"Todd W. Dowrey,&nbsp;Samuel F. Cranston,&nbsp;Nicholas Skvir,&nbsp;Yvonne Lok,&nbsp;Brian Gould,&nbsp;Bradley Petrowitz,&nbsp;Daniel Villar,&nbsp;Jidong Shan,&nbsp;Marianne James,&nbsp;Mark Dodge,&nbsp;Anna C. Belkina,&nbsp;Richard M. Giadone,&nbsp;Sofiya Milman,&nbsp;Paola Sebastiani,&nbsp;Thomas T. Perls,&nbsp;Stacy L. Andersen,&nbsp;George J. Murphy","doi":"10.1111/acel.14479","DOIUrl":"https://doi.org/10.1111/acel.14479","url":null,"abstract":"<p>Cover legend: The cover image is based on the article <i>A longevity-specific bank of induced pluripotent stem cells from centenarians and their offspring</i> by George Murphy et al., https://doi.org/10.1111/acel.14351.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14479","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143113083","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Additional Cover
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14480
Nathalie Launay, Maria Espinosa-Alcantud, Edgard Verdura, Gorka Fernández-Eulate, Jon Ondaro, Pablo Iruzubieta, Maria Marsal, Agatha Schlüter, Montserrat Ruiz, Stephane Fourcade, Agustí Rodríguez-Palmero, Miren Zulaica, Andone Sistiaga, Garazi Labayru, Pablo Loza-Alvarez, Alejandro Vaquero, Adolfo Lopez de Munain, Aurora Pujol
{"title":"Additional Cover","authors":"Nathalie Launay,&nbsp;Maria Espinosa-Alcantud,&nbsp;Edgard Verdura,&nbsp;Gorka Fernández-Eulate,&nbsp;Jon Ondaro,&nbsp;Pablo Iruzubieta,&nbsp;Maria Marsal,&nbsp;Agatha Schlüter,&nbsp;Montserrat Ruiz,&nbsp;Stephane Fourcade,&nbsp;Agustí Rodríguez-Palmero,&nbsp;Miren Zulaica,&nbsp;Andone Sistiaga,&nbsp;Garazi Labayru,&nbsp;Pablo Loza-Alvarez,&nbsp;Alejandro Vaquero,&nbsp;Adolfo Lopez de Munain,&nbsp;Aurora Pujol","doi":"10.1111/acel.14480","DOIUrl":"https://doi.org/10.1111/acel.14480","url":null,"abstract":"<p>Cover legend: The cover image is based on the article <i>Altered tubulin detyrosination due to SVBP malfunction induces cytokinesis failure and senescence, underlying a complex\u0000hereditary spastic paraplegia</i> by Aurora Pujol et al., https://doi.org/10.1111/acel.14355.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14480","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143113084","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Featured Cover
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-08 DOI: 10.1111/acel.14478
Yu Li, Jinxin Qi, Linhong Guo, Xian Jiang, Gu He
{"title":"Featured Cover","authors":"Yu Li,&nbsp;Jinxin Qi,&nbsp;Linhong Guo,&nbsp;Xian Jiang,&nbsp;Gu He","doi":"10.1111/acel.14478","DOIUrl":"https://doi.org/10.1111/acel.14478","url":null,"abstract":"<p>Cover legend: The cover image is based on the article <i>Organellar quality control crosstalk in aging-related disease: Innovation to pave the way</i> by Gu He et al.,\u0000https://doi.org/10.1111/acel.14447.\u0000\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure>\u0000 </p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 1","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14478","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143113076","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate Efferocytosis:衰老和肿瘤命运的双面守门人。
IF 7.8 1区 医学
Aging Cell Pub Date : 2025-01-03 DOI: 10.1111/acel.14467
Zaoqu Liu, Yan Li, Yuqing Ren, Jingqi Chen, Siyuan Weng, Zhaokai Zhou, Peng Luo, Quan Chen, Hui Xu, Yuhao Ba, Anning Zuo, Shutong Liu, Yuyuan Zhang, Teng Pan, Xinwei Han
{"title":"Efferocytosis: The Janus-Faced Gatekeeper of Aging and Tumor Fate","authors":"Zaoqu Liu,&nbsp;Yan Li,&nbsp;Yuqing Ren,&nbsp;Jingqi Chen,&nbsp;Siyuan Weng,&nbsp;Zhaokai Zhou,&nbsp;Peng Luo,&nbsp;Quan Chen,&nbsp;Hui Xu,&nbsp;Yuhao Ba,&nbsp;Anning Zuo,&nbsp;Shutong Liu,&nbsp;Yuyuan Zhang,&nbsp;Teng Pan,&nbsp;Xinwei Han","doi":"10.1111/acel.14467","DOIUrl":"10.1111/acel.14467","url":null,"abstract":"<p>From embryogenesis to aging, billions of cells perish daily in mammals. The multistep process by which phagocytes engulf these deceased cells without eliciting an inflammatory response is called efferocytosis. Despite significant insights into the fundamental mechanisms of efferocytosis, its implications in disorders such as aging and cancer remain elusive. Upon summarizing and analyzing existing studies on efferocytosis, it becomes evident that efferocytosis is our friend in resolving inflammation, yet it transforms into our foe by facilitating tumor development and metastasis. This review illuminates recent discoveries regarding the emerging mechanisms of efferocytosis in clearing apoptotic cells, explores its connections with aging, examines its influence on tumor development and metastasis, and identifies the regulatory factors of efferocytosis within the tumor microenvironment. A comprehensive understanding of these efferocytosis facets offers insights into crucial physiological and pathophysiological processes, paving the way for innovative therapeutic approaches to combat aging and cancer.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 2","pages":""},"PeriodicalIF":7.8,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14467","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142918678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation-mediated premature senescence 过表达Cockayne综合征B组蛋白的人皮肤成纤维细胞亚群可抵抗UVB辐射介导的过早衰老。
IF 7.8 1区 医学
Aging Cell Pub Date : 2024-12-19 DOI: 10.1111/acel.14422
Asimina Fotopoulou, Maria T. Angelopoulou, Harris Pratsinis, Eleni Mavrogonatou, Dimitris Kletsas
{"title":"A subset of human dermal fibroblasts overexpressing Cockayne syndrome group B protein resist UVB radiation-mediated premature senescence","authors":"Asimina Fotopoulou,&nbsp;Maria T. Angelopoulou,&nbsp;Harris Pratsinis,&nbsp;Eleni Mavrogonatou,&nbsp;Dimitris Kletsas","doi":"10.1111/acel.14422","DOIUrl":"10.1111/acel.14422","url":null,"abstract":"<p>Ultraviolet B (UVB) radiation is a major contributor to skin photoaging. Although mainly absorbed by the epidermis, UVB photons managing to penetrate the upper dermis affect human dermal fibroblasts (HDFs), leading, among others, to the accumulation of senescent cells. In vitro studies have shown that repeated exposures to subcytotoxic UVB radiation doses provoke HDFs' premature senescence shortly after the end of the treatment period. Here, we found that repetitive exposures to non-cytotoxic UVB radiation doses after several days lead to mixed cultures, containing both senescent cells and fibroblasts resisting senescence. “Resistant” fibroblasts were more resilient to a novel intense UVB radiation stimulus. RNA-seq analysis revealed that ERCC6, encoding Cockayne syndrome group B (CSB) protein, is up-regulated in resistant HDFs compared to young and senescent cells. CSB was found to be a key molecule conferring protection toward UVB-induced cytotoxicity and senescence, as siRNA-mediated CSB loss-of-expression rendered HDFs significantly more susceptible to a high UVB radiation dose, while cells from a CSB-deficient patient were found to be more sensitive to UVB-mediated toxicity, as well as senescence. UVB-resistant HDFs remained normal (able to undergo replicative senescence) and non-tumorigenic. Even though they formed a distinct population in-between young and senescent cells, resistant HDFs retained numerous tissue-impairing characteristics of the senescence-associated secretory phenotype, including increased matrix metalloprotease activity and promotion of epidermoid tumor xenografts in immunodeficient mice. Collectively, here we describe a novel subpopulation of HDFs showing increased resistance to UVB-mediated premature senescence while retaining undesirable traits that may negatively affect skin homeostasis.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14422","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851654","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny 增加线粒体突变异质性诱导多能干细胞及其分化后代的衰老表型。
IF 7.8 1区 医学
Aging Cell Pub Date : 2024-12-16 DOI: 10.1111/acel.14402
Amy R. Vandiver, Alejandro Torres Jr, Amberly Sanden, Thang L. Nguyen, Jasmine Gasilla, Mary T. Doan, Vahan Martirosian, Austin Hoang, Jonathan Wanagat, Michael A. Teitell
{"title":"Increased mitochondrial mutation heteroplasmy induces aging phenotypes in pluripotent stem cells and their differentiated progeny","authors":"Amy R. Vandiver,&nbsp;Alejandro Torres Jr,&nbsp;Amberly Sanden,&nbsp;Thang L. Nguyen,&nbsp;Jasmine Gasilla,&nbsp;Mary T. Doan,&nbsp;Vahan Martirosian,&nbsp;Austin Hoang,&nbsp;Jonathan Wanagat,&nbsp;Michael A. Teitell","doi":"10.1111/acel.14402","DOIUrl":"10.1111/acel.14402","url":null,"abstract":"<p>The mitochondrial genome (mtDNA) is an important source of inherited extranuclear variation. Clonal increases in mtDNA mutation heteroplasmy have been implicated in aging and disease, although the impact of this shift on cell function is challenging to assess. Reprogramming to pluripotency affects mtDNA mutation heteroplasmy. We reprogrammed three human fibroblast lines with known heteroplasmy for deleterious mtDNA point or deletion mutations. Quantification of mutation heteroplasmy in the resulting 76 induced pluripotent stem cell (iPSC) clones yielded a bimodal distribution, creating three sets of clones with high levels or absent mutation heteroplasmy with matched nuclear genomes. iPSC clones with elevated deletion mutation heteroplasmy show altered growth dynamics, which persist in iPSC-derived progenitor cells. We identify transcriptomic and metabolic shifts consistent with increased investment in neutral lipid synthesis as well as increased epigenetic age in high mtDNA deletion mutation iPSC, consistent with changes occurring in cellular aging. Together, these data demonstrate that high mtDNA mutation heteroplasmy induces changes occurring in cellular aging.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"24 3","pages":""},"PeriodicalIF":7.8,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14402","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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