Aging Cell最新文献_第5页

Single-neuron analysis of aging-associated changes in learning reveals impairments in transcriptional plasticity 对衰老相关学习变化的单神经元分析揭示了转录可塑性的损伤。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-24 DOI: 10.1111/acel.14228

Kerriann K. Badal, Abhishek Sadhu, Bindu L. Raveendra, Carrie McCracken, Sebastian Lozano-Villada, Amol C. Shetty, Phillip Gillette, Yibo Zhao, Dustin Stommes, Lynne A. Fieber, Michael C. Schmale, Anup Mahurkar, Robert D. Hawkins, Sathyanarayanan V. Puthanveettil

{"title":"Single-neuron analysis of aging-associated changes in learning reveals impairments in transcriptional plasticity","authors":"Kerriann K. Badal, Abhishek Sadhu, Bindu L. Raveendra, Carrie McCracken, Sebastian Lozano-Villada, Amol C. Shetty, Phillip Gillette, Yibo Zhao, Dustin Stommes, Lynne A. Fieber, Michael C. Schmale, Anup Mahurkar, Robert D. Hawkins, Sathyanarayanan V. Puthanveettil","doi":"10.1111/acel.14228","DOIUrl":"10.1111/acel.14228","url":null,"abstract":"The molecular mechanisms underlying age-related declines in learning and long-term memory are still not fully understood. To address this gap, our study focused on investigating the transcriptional landscape of a singularly identified motor neuron L7 in Aplysia, which is pivotal in a specific type of nonassociative learning known as sensitization of the siphon-withdraw reflex. Employing total RNAseq analysis on a single isolated L7 motor neuron after short-term or long-term sensitization (LTS) training of Aplysia at 8, 10, and 12 months (representing mature, late mature, and senescent stages), we uncovered aberrant changes in transcriptional plasticity during the aging process. Our findings specifically highlight changes in the expression of messenger RNAs (mRNAs) that encode transcription factors, translation regulators, RNA methylation participants, and contributors to cytoskeletal rearrangements during learning and long noncoding RNAs (lncRNAs). Furthermore, our comparative gene expression analysis identified distinct transcriptional alterations in two other neurons, namely the motor neuron L11 and the giant cholinergic neuron R2, whose roles in LTS are not yet fully elucidated. Taken together, our analyses underscore cell type-specific impairments in the expression of key components related to learning and memory within the transcriptome as organisms age, shedding light on the complex molecular mechanisms driving cognitive decline during aging.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14228","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141453857","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

Cellular senescence by loss of Men1 in osteoblasts is critical for age-related osteoporosis 成骨细胞中 Men1 的缺失导致的细胞衰老对老年性骨质疏松症至关重要

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-22 DOI: 10.1111/acel.14254

Yuichiro Ukon, Takashi Kaito, Hiromasa Hirai, Takayuki Kitahara, Masayuki Bun, Joe Kodama, Daisuke Tateiwa, Shinichi Nakagawa, Masato Ikuta, Takuya Furuichi, Yuya Kanie, Takahito Fujimori, Shota Takenaka, Tadashi Yamamuro, Satoru Otsuru, Seiji Okada, Masakatsu Yamashita, Takeshi Imamura

{"title":"Cellular senescence by loss of Men1 in osteoblasts is critical for age-related osteoporosis","authors":"Yuichiro Ukon, Takashi Kaito, Hiromasa Hirai, Takayuki Kitahara, Masayuki Bun, Joe Kodama, Daisuke Tateiwa, Shinichi Nakagawa, Masato Ikuta, Takuya Furuichi, Yuya Kanie, Takahito Fujimori, Shota Takenaka, Tadashi Yamamuro, Satoru Otsuru, Seiji Okada, Masakatsu Yamashita, Takeshi Imamura","doi":"10.1111/acel.14254","DOIUrl":"10.1111/acel.14254","url":null,"abstract":"Recent evidence suggests an association between age-related osteoporosis and cellular senescence in the bone; however, the specific bone cells that play a critical role in age-related osteoporosis and the mechanism remain unknown. Results revealed that age-related osteoporosis is characterized by the loss of osteoblast Men1. Osteoblast-specific inducible knockout of Men1 caused structural changes in the mice bones, matching the phenotypes in patients with age-related osteoporosis. Histomorphometrically, Men1-knockout mice femurs decreased osteoblastic activity and increased osteoclastic activity, hallmarks of age-related osteoporosis. Loss of Men1 induces cellular senescence via mTORC1 activation and AMPK suppression, rescued by metformin treatment. In bone morphogenetic protein-indued bone model, loss of Men1 leads to accumulation of senescent cells and osteoporotic bone formation, which are ameliorated by metformin. Our results indicate that cellular senescence in osteoblasts plays a critical role in age-related osteoporosis and that osteoblast-specific inducible Men1-knockout mice offer a promising model for developing therapeutics for age-related osteoporosis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14254","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522502","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 new gene signature for endothelial senescence identifies self-RNA sensing by retinoic acid-inducible gene I as a molecular facilitator of vascular aging 内皮衰老的新基因特征表明，视黄酸诱导基因 I 的自我 RNA 感知是血管衰老的分子促进因素

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-21 DOI: 10.1111/acel.14240

Jasenka Guduric-Fuchs, Edoardo Pedrini, Pietro M. Bertelli, Shannon McDonnell, Varun Pathak, Kiran McLoughlin, Christina L. O'Neill, Alan W. Stitt, Reinhold J. Medina

{"title":"A new gene signature for endothelial senescence identifies self-RNA sensing by retinoic acid-inducible gene I as a molecular facilitator of vascular aging","authors":"Jasenka Guduric-Fuchs, Edoardo Pedrini, Pietro M. Bertelli, Shannon McDonnell, Varun Pathak, Kiran McLoughlin, Christina L. O'Neill, Alan W. Stitt, Reinhold J. Medina","doi":"10.1111/acel.14240","DOIUrl":"10.1111/acel.14240","url":null,"abstract":"The number of senescent vascular endothelial cells increases during aging and their dysfunctional phenotype contributes to age-related cardiovascular disease. Identification of senescent cells is challenging as molecular changes are often tissue specific and occur amongst clusters of normal cells. Here, we established, benchmarked, and validated a new gene signature called EndoSEN that pinpoints senescent endothelial cells. The EndoSEN signature was enriched for interferon-stimulated genes (ISG) and correlated with the senescence-associated secretory phenotype (SASP). SASP establishment is classically attributed to DNA damage and cyclic GMP–AMP synthase activation, but our results revealed a pivotal role for RNA accumulation and sensing in senescent endothelial cells. Mechanistically, we showed that endothelial cell senescence hallmarks include self-RNA accumulation, RNA sensor RIG-I upregulation, and an ISG signature. Moreover, a virtual model of RIG-I knockout in endothelial cells underscored senescence as a key pathway regulated by this sensor. We tested and confirmed that RIG-I knockdown was sufficient to extend the lifespan and decrease the SASP in endothelial cells. Taken together, our evidence suggests that targeting RNA sensing is a potential strategy to delay vascular aging.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14240","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522503","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

Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts 晶状体囊高级糖化终产物诱导上皮细胞衰老：对继发性白内障的影响

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-21 DOI: 10.1111/acel.14249

Grace Cooksley, Mi-Hyun Nam, Rooban B. Nahomi, Johanna Rankenberg, Andrew J. O. Smith, Yvette M. Wormstone, I. Michael Wormstone, Ram H. Nagaraj

{"title":"Lens capsule advanced glycation end products induce senescence in epithelial cells: Implications for secondary cataracts","authors":"Grace Cooksley, Mi-Hyun Nam, Rooban B. Nahomi, Johanna Rankenberg, Andrew J. O. Smith, Yvette M. Wormstone, I. Michael Wormstone, Ram H. Nagaraj","doi":"10.1111/acel.14249","DOIUrl":"10.1111/acel.14249","url":null,"abstract":"Posterior capsule opacification (PCO) is a common complication after cataract surgery. Residual lens epithelial cells (LECs) on the anterior lens capsule, after cataract surgery, migrate to the posterior lens capsule and undergo transdifferentiation into myofibroblast-like cells. Those cells synthesize excessive amounts of extracellular matrix and contribute to fibrosis during PCO. Cellular senescence, a phenomenon that increases with aging, has been implicated in several fibrotic diseases. Here, we have investigated the prevalence of senescent LECs within the lens posterior capsule and the ability of advanced glycation end products (AGEs) in lens capsules to induce senescence, contributing to PCO. Aged lens capsules from pseudophakic human cadaver eyes showed the presence of senescent LECs. In human capsular bags, LECs showed an age-dependent increase in senescence after 28 days of culture. Human LECs cultured on aged lens capsules for 3 days underwent senescence; this effect was not seen in LECs cultured on young lens capsules. Human LECs cultured on an AGE-modified extracellular matrix (ECM-AGEs) showed an AGE-concentration-dependent increase in the expression of senescence markers and reactive oxygen species (ROS) levels. Treatment with a RAGE antagonist and ROS inhibitor reduced the expression of senescence and fibrotic markers. Additionally, conditioned media from ECM-AGEs-treated cells induced the expression of fibrotic markers in naïve LECs. Together, these suggest that AGEs in the capsule induce senescence of LECs, which triggers the mesenchymal transition of neighboring non-senescent LECs and contributes to PCO.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14249","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522504","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

Achilles' spear: A new therapeutic target for age-related diseases 阿喀琉斯之矛老年相关疾病的新治疗靶点

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-21 DOI: 10.1111/acel.14257

Yang Xuan, Yue Duan

引用次数: 0

Single-cell mitochondrial sequencing reveals low-frequency mitochondrial mutations in naturally aging mice 单细胞线粒体测序揭示自然衰老小鼠的低频线粒体突变

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-21 DOI: 10.1111/acel.14242

Fuyan Liu, Xiaolin Sun, Cai Wei, Liu Ji, Yali Song, Chenlu Yang, Yue Wang, Xin Liu, Daqing Wang, Jingmin Kang

{"title":"Single-cell mitochondrial sequencing reveals low-frequency mitochondrial mutations in naturally aging mice","authors":"Fuyan Liu, Xiaolin Sun, Cai Wei, Liu Ji, Yali Song, Chenlu Yang, Yue Wang, Xin Liu, Daqing Wang, Jingmin Kang","doi":"10.1111/acel.14242","DOIUrl":"10.1111/acel.14242","url":null,"abstract":"Mitochondria play a crucial role in numerous biological processes; however, limited methods and research have focused on revealing mitochondrial heterogeneity at the single-cell level. In this study, we optimized the DNBelab C4 single-cell ATAC (assay for transposase-accessible chromatin) sequencing workflow for single-cell mitochondrial sequencing (C4_mtscATAC-seq). We validated the effectiveness of our C4_mtscATAC-seq protocol by sequencing the HEK-293T cell line with two biological replicates, successfully capturing both mitochondrial content (~68% of total sequencing data) and open chromatin status simultaneously. Subsequently, we applied C4_mtscATAC-seq to investigate two mouse tissues, spleen and bone marrow, obtained from two mice aged 2 months and two mice aged 23 months. Our findings revealed higher mitochondrial DNA (mtDNA) content in young tissues compared to more variable mitochondrial content in aged tissues, consistent with higher activity scores of nuclear genes associated with mitochondrial replication and transcription in young tissues. We detected a total of 22, 15, and 21 mtDNA mutations in the young spleen, aged spleen, and bone marrow, respectively, with most variant allele frequencies (VAF) below 1%. Moreover, we observed a higher number of mtDNA mutations with higher VAF in aged tissues compared to young tissues. Importantly, we identified three mtDNA variations (m.9821A>T, m.15219T>C, and m.15984C>T) with the highest VAF in both aged spleen and aged bone marrow. By comparing cells with and without these mtDNA variations, we analyzed differential open chromatin status to identify potential genes associated with these mtDNA variations, including transcription factors such as KLF15 and NRF1. Our study presents an alternative single-cell mitochondrial sequencing method and provides crude insights into age-related single-cell mitochondrial variations.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14242","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141522506","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

Prophylactic senolytic treatment in aged mice reduces seizure severity and improves survival from Status Epilepticus 对老年小鼠进行预防性溶酶治疗可降低癫痫发作的严重程度并提高癫痫状态的存活率

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-20 DOI: 10.1111/acel.14239

Tahiyana Khan, Abbas I. Hussain, Timothy P. Casilli, Logan Frayser, Michelle Cho, Gabrielle Williams, David McFall, Patrick A. Forcelli

{"title":"Prophylactic senolytic treatment in aged mice reduces seizure severity and improves survival from Status Epilepticus","authors":"Tahiyana Khan, Abbas I. Hussain, Timothy P. Casilli, Logan Frayser, Michelle Cho, Gabrielle Williams, David McFall, Patrick A. Forcelli","doi":"10.1111/acel.14239","DOIUrl":"10.1111/acel.14239","url":null,"abstract":"Increased vulnerability to seizures in aging has been well documented both clinically and in various models of aging in epilepsy. Seizures can exacerbate cognitive decline that is already prominent in aging. Senescent cells are thought to contribute to cognitive impairment in aging and clearing senescent cells with senolytic drugs improves cognitive function in animal models. It remains unclear whether senescent cells render the aged brain vulnerable to seizures. Here, we demonstrate that prophylactic senolytic treatment with Dasatinib and Quercetin (D&Q) reduced both seizure severity and mortality in aged C57BL/6J mice. We subjected the D&Q and VEH-treated aged mice to spatial memory testing before and after an acute seizure insult, Status Epilepticus [SE], which leads to epilepsy development. We found that senolytic therapy improved spatial memory before injury, however, spatial memory was not rescued after SE. Senescence-related proteins p16 and senescence-associated β-galactosidase were reduced in D&Q-treated aged mice. Our findings indicate that senescent cells increase seizure susceptibility in aging. Thus, prophylactically targeting senescent cells may prevent age-related seizure vulnerability.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.14239","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141503918","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

Aging-induced short-chain acyl-CoA dehydrogenase promotes age-related hepatic steatosis by suppressing lipophagy 衰老诱导的短链酰基-CoA脱氢酶通过抑制噬脂作用促进与衰老相关的肝脂肪变性。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-19 DOI: 10.1111/acel.14256

Dan Deng, Shanshan Yang, Xiaoqian Yu, Ruixue Zhou, Yin Liu, Hongmei Zhang, Daxin Cui, Xingrong Feng, Yanting Wu, Xiaocun Qi, Zhiguang Su

{"title":"Aging-induced short-chain acyl-CoA dehydrogenase promotes age-related hepatic steatosis by suppressing lipophagy","authors":"Dan Deng, Shanshan Yang, Xiaoqian Yu, Ruixue Zhou, Yin Liu, Hongmei Zhang, Daxin Cui, Xingrong Feng, Yanting Wu, Xiaocun Qi, Zhiguang Su","doi":"10.1111/acel.14256","DOIUrl":"10.1111/acel.14256","url":null,"abstract":"Hepatic steatosis, the first step in the development of nonalcoholic fatty liver disease (NAFLD), is frequently observed in the aging population. However, the underlying molecular mechanism remains largely unknown. In this study, we first employed GSEA enrichment analysis to identify short-chain acyl-CoA dehydrogenase (SCAD), which participates in the mitochondrial β-oxidation of fatty acids and may be associated with hepatic steatosis in elderly individuals. Subsequently, we examined SCAD expression and hepatic triglyceride content in various aged humans and mice and found that triglycerides were markedly increased and that SCAD was upregulated in aged livers. Our further evidence in SCAD-ablated mice suggested that SCAD deletion was able to slow liver aging and ameliorate aging-associated fatty liver. Examination of the molecular pathways by which the deletion of SCAD attenuates steatosis revealed that the autophagic degradation of lipid droplets, which was not detected in elderly wild-type mice, was maintained in SCAD-deficient old mice. This was due to the decrease in the production of acetyl-coenzyme A (acetyl-CoA), which is abundant in the livers of old wild-type mice. In conclusion, our findings demonstrate that the suppression of SCAD may prevent age-associated hepatic steatosis by promoting lipophagy and that SCAD could be a promising therapeutic target for liver aging and associated steatosis.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464120/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141425795","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

Age-dependent heat shock hormesis to HSF-1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans 年龄依赖性热休克激素对 HSF-1 缺乏的影响表明，年轻的秀丽隐杆线虫体内存在一种由未折叠蛋白反应和先天性免疫介导的补偿机制。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-19 DOI: 10.1111/acel.14246

Dániel Kovács, János Barnabás Biró, Saqib Ahmed, Márton Kovács, Tímea Sigmond, Bernadette Hotzi, Máté Varga, Viktor Vázsony Vincze, Umar Mohammad, Tibor Vellai, János Barna

{"title":"Age-dependent heat shock hormesis to HSF-1 deficiency suggests a compensatory mechanism mediated by the unfolded protein response and innate immunity in young Caenorhabditis elegans","authors":"Dániel Kovács, János Barnabás Biró, Saqib Ahmed, Márton Kovács, Tímea Sigmond, Bernadette Hotzi, Máté Varga, Viktor Vázsony Vincze, Umar Mohammad, Tibor Vellai, János Barna","doi":"10.1111/acel.14246","DOIUrl":"10.1111/acel.14246","url":null,"abstract":"The transcription factor HSF-1 (heat shock factor 1) acts as a master regulator of heat shock response in eukaryotic cells to maintain cellular proteostasis. The protein has a protective role in preventing cells from undergoing ageing, and neurodegeneration, and also mediates tumorigenesis. Thus, modulating HSF-1 activity in humans has a promising therapeutic potential for treating these pathologies. Loss of HSF-1 function is usually associated with impaired stress tolerance. Contrary to this conventional knowledge, we show here that inactivation of HSF-1 in the nematode Caenorhabditis elegans results in increased thermotolerance at young adult stages, whereas HSF-1 deficiency in animals passing early adult stages indeed leads to decreased thermotolerance, as compared to wild-type. Furthermore, a gene expression analysis supports that in young adults, distinct cellular stress response and immunity-related signaling pathways become induced upon HSF-1 deficiency. We also demonstrate that increased tolerance to proteotoxic stress in HSF-1-depleted young worms requires the activity of the unfolded protein response of the endoplasmic reticulum and the SKN-1/Nrf2-mediated oxidative stress response pathway, as well as an innate immunity-related pathway, suggesting a mutual compensatory interaction between HSF-1 and these conserved stress response systems. A similar compensatory molecular network is likely to also operate in higher animal taxa, raising the possibility of an unexpected outcome when HSF-1 activity is manipulated in humans.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464127/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416864","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

Deficiency of SECTM1 impairs corneal wound healing in aging 缺乏 SECTM1 会影响衰老过程中角膜伤口的愈合。

IF 7.8 1区医学

Aging Cell Pub Date : 2024-06-17 DOI: 10.1111/acel.14247

Jin Zhu, Xihong Lan, Kunlun Mo, Wang Zhang, Ying Huang, Jieying Tan, Li Wang, Jianping Ji, Qiong Ke, Hong Ouyang

{"title":"Deficiency of SECTM1 impairs corneal wound healing in aging","authors":"Jin Zhu, Xihong Lan, Kunlun Mo, Wang Zhang, Ying Huang, Jieying Tan, Li Wang, Jianping Ji, Qiong Ke, Hong Ouyang","doi":"10.1111/acel.14247","DOIUrl":"10.1111/acel.14247","url":null,"abstract":"The corneal epithelium is the outermost transparent barrier of the eyeball and undergoes continuous self-renewal by limbal stem cells (LSCs) during its lifetime; however, the impact of aging on LSCs remains largely unknown. Here, we showed that the healing ability of the cornea in elderly macaques (Macaca fascicularis) was significantly decreased compared to that of younger macaques. This delayed wound closure accompanied a disordered cell arrangement and corneal opacity. A novel cytokine, Secreted and Transmembrane 1 (SECTM1), was found to facilitate corneal healing and was upregulated in young macaques upon wounding. Mechanistically, SECTM1 is essential for LSC migration and proliferation, and may partially function through Cell Division Cycle Associated 7 (CDCA7). Notably, the topical application of SECTM1 to aged wounded corneas dramatically promoted re-epithelialization and improved corneal transparency in both mice and macaques. Our work suggests that aging may impair the expression of healing response factors and injury repair in non-human primate corneas, and that SECTM1 application could potentially benefit corneal wound healing in clinical treatment.","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":null,"pages":null},"PeriodicalIF":7.8,"publicationDate":"2024-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464118/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141416865","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