Aging (Albany NY)最新文献_第4页

Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells 敲除amd相关基因POLDIP2可降低人视网膜色素上皮细胞线粒体超氧化物

Aging (Albany NY) Pub Date : 2022-07-06 DOI: 10.1101/2022.07.05.498910

Tu Nguyen, Daniel Urrutia-Cabrera, Luozixian Wang, J. Lees, Jiang-Hui Wang, Sandy S. C. Hung, A. Hewitt, T. L. Edwards, S. McLenachan, F. Chen, Shiang Y. Lim, C. Luu, R. Guymer, Raymond C. B. Wong

{"title":"Knockout of AMD-associated gene POLDIP2 reduces mitochondrial superoxide in human retinal pigment epithelial cells","authors":"Tu Nguyen, Daniel Urrutia-Cabrera, Luozixian Wang, J. Lees, Jiang-Hui Wang, Sandy S. C. Hung, A. Hewitt, T. L. Edwards, S. McLenachan, F. Chen, Shiang Y. Lim, C. Luu, R. Guymer, Raymond C. B. Wong","doi":"10.1101/2022.07.05.498910","DOIUrl":"https://doi.org/10.1101/2022.07.05.498910","url":null,"abstract":"Genetic and epidemiologic studies have significantly advanced our understanding of the genetic factors contributing to age-related macular degeneration (AMD). In particular, recent expression quantitative trait loci (eQTL) studies have highlighted POLDIP2 as a significant gene that confers risk of developing AMD. However, the role of POLDIP2 in retinal cells such as retinal pigment epithelium (RPE) and how it contributes to AMD pathology are unknown. Here we report the generation of a stable human RPE cell line with POLDIP2 knockout using CRISPR/Cas, providing an in vitro model to investigate the functions of POLDIP2. We conducted functional studies on the POLDIP2 knockout cell line and showed that they retained normal levels of cell proliferation, cell viability, phagocytosis and autophagy. Also, we performed RNA sequencing to profile the transcriptome of POLDIP2 knockout cells. Our results highlighted significant changes in genes involved in immune response, complement activation, oxidative damage and vascular development. We showed that loss of POLDIP2 causes a reduction in mitochondrial superoxide levels, which is consistent with the upregulation of the mitochondrial superoxide dismutase SOD2. In conclusion, this study demonstrates a novel link between POLDIP2 and SOD2, which supports a potential role of POLDIP2 in regulating oxidative stress in AMD pathology.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"14 1","pages":"1713 - 1733"},"PeriodicalIF":0.0,"publicationDate":"2022-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81931586","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Differential impact of glycemic control and comorbid conditions on the neurophysiology underlying task switching in older adults with type 2 diabetes 血糖控制和合并症对老年2型糖尿病神经生理学潜在任务转换的不同影响

Aging (Albany NY) Pub Date : 2022-06-17 DOI: 10.18632/aging.204129

C. Embury, G. Lord, A. Drincic, C. Desouza, T. Wilson

{"title":"Differential impact of glycemic control and comorbid conditions on the neurophysiology underlying task switching in older adults with type 2 diabetes","authors":"C. Embury, G. Lord, A. Drincic, C. Desouza, T. Wilson","doi":"10.18632/aging.204129","DOIUrl":"https://doi.org/10.18632/aging.204129","url":null,"abstract":"Type 2 diabetes is known to negatively affect higher order cognition and the brain, but the underlying mechanisms are not fully understood. In particular, glycemic control and common comorbidities are both thought to contribute to alterations in cortical neurophysiology in type 2 diabetes, but their specific impact remains unknown. The current study probed the dynamics underlying cognitive control in older participants with type 2 diabetes, with and without additional comorbid conditions (i.e., cardiovascular disease, nephropathy, peripheral neuropathy, retinopathy), using a task switching paradigm and a dynamic functional brain mapping method based on magnetoencephalography (MEG). We hypothesized that neural dynamics would be differentially impacted by the level of glycemic control (i.e., diabetes itself) and the burden of additional comorbid conditions. Supporting this hypothesis, our findings indicated separable, but widespread alterations across frontal, parietal, temporal and cerebellum regions in neural task-switch costs in type 2 diabetes that were differentially attributable to glycemic control and the presence of comorbid conditions. These effects were spatially non-overlapping and the effects were not statistically related to one another. Further, several of the effects that were related to the presence of comorbidities were associated with behavioral performance, indicating progressive deficits in brain function with extended disease. These findings provide insight on the underlying neuropathology and may inform future treatment plans to curtail the neural impact of type 2 diabetes.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"96 1","pages":"4976 - 4989"},"PeriodicalIF":0.0,"publicationDate":"2022-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85304950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Janus-faced citrate in aging and metabolism 柠檬酸对衰老和新陈代谢的影响

Aging (Albany NY) Pub Date : 2022-06-17 DOI: 10.18632/aging.204138

Wei-Sheng Lin, Pei-Yu Wang

引用次数: 0

The minor allele of rs17427875 in long non-coding RNA-HOXA11-AS influences the prognosis of subarachnoid hemorrhage (SAH) via modulating miR-15a and STAT3 expression 长链非编码RNA-HOXA11-AS中rs17427875的次要等位基因通过调节miR-15a和STAT3的表达影响蛛网膜下腔出血(SAH)的预后

Aging (Albany NY) Pub Date : 2022-06-14 DOI: 10.18632/aging.204126

Yong Zhou, Zhiming Xu, Shengli Li

{"title":"The minor allele of rs17427875 in long non-coding RNA-HOXA11-AS influences the prognosis of subarachnoid hemorrhage (SAH) via modulating miR-15a and STAT3 expression","authors":"Yong Zhou, Zhiming Xu, Shengli Li","doi":"10.18632/aging.204126","DOIUrl":"https://doi.org/10.18632/aging.204126","url":null,"abstract":"Background: HOAX11-AS was reported to promote the progression of liver cancer via the signaling pathway of miR-15a-3p/STAT3. In this study, we investigated the effect of rs17427875 on the prognosis of subarachnoid hemorrhage (SAH) and its underlying molecular mechanisms. Methods: 158 SAH patients were recruited and grouped according to their genotypes rs17427875. Peripheral blood and cerebrospinal fluid (CSF) samples were collected for subsequent analysis. Quantitative real-time PCR, luciferase assays, Western blot and ELISA were performed to analyze the correlations between the expression of lncRNA-HOXA11-AS, miR-15a, TNF-α and NF-κB. Results: The survival rate was remarkably higher in SAH patients carrying the AA genotype of rs17427875 when compared with those carrying the AT genotype. The expression of miR-15a was significantly repressed in the peripheral blood and CSF of SAH patients carrying the AT allele when compared with that in patients carrying the AA allele. MiR-15a showed a remarkable efficacy in inhibiting the luciferase activity of wild type lncRNA-HOXA11-AS and STAT3 in THP-1 cells. P-HOXA11-AS-T showed a stronger ability to suppress the expression of miR-15a and activate the expression of STAT3, TNF-α and NF-κB in THP-1 cells when compared with P-HOXA11-AS-A. Conclusions: The findings demonstrated that the presence of the minor allele of rs17427875 in lncRNA-HOXA11-AS could increase the expression level of lncRNA-HOXA11-AS, thus elevating the expression level of STAT3 via down-regulating miR-15a, and increased STAT3 expression could aggravate inflammation to cause poor prognosis of SAH. Therefore, the rs17427875 polymorphism can be used as a potential biomarker for the prognosis of SAH.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"16 1","pages":"5075 - 5085"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79123538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149/Smad2 axis 环状RNA hsa_circ_0003091通过海绵化miR-149/Smad2轴调控败血症诱导的肺损伤

Aging (Albany NY) Pub Date : 2022-06-14 DOI: 10.18632/aging.204125

Mei-jia Shen, Shengtao Yan, Xiao-yan Zhang, Wen Li, Xu Chen, Xiaotuo Zheng, Guo-qiang Zhang, Lichao Sun

{"title":"The circular RNA hsa_circ_0003091 regulates sepsis-induced lung injury by sponging the miR-149/Smad2 axis","authors":"Mei-jia Shen, Shengtao Yan, Xiao-yan Zhang, Wen Li, Xu Chen, Xiaotuo Zheng, Guo-qiang Zhang, Lichao Sun","doi":"10.18632/aging.204125","DOIUrl":"https://doi.org/10.18632/aging.204125","url":null,"abstract":"Sepsis-induced acute lung injury (ALI) is a severe cause of death. Increasing evidence has identified circular RNAs (circRNAs) acting as critical regulators of human diseases. However, their expression pattern and underlying mechanisms in ALI remain unclear. Herein, we screened the circRNAs of ALI patients and constructed a lung injury murine model using lipopolysaccharides (LPS) induction. Functional analyses of targeted circRNA were performed in vivo and in vitro. Then, the downstream miRNA and mRNA of specific circRNAs were identified. Compared to healthy subjects, 35 circRNAs were upregulated and 9 circRNAs were downregulated in sepsis patients. The top 10 differentially expressed circRNAs were selected for validation and has_circ_0003091 was selected. The ALI mice presented significantly elevated has_circ_0003091 (mmu_circ_0015268). The functional analysis revealed that mmu_circ_0015268 contributed to the pulmonary injury, cell apoptosis, inflammatory responses, and endothelial activation in the ALI murine model. On the other hand, silencing mmu_circ_0015268 showed protective effects in LPS-treated mice and PMVECs. Furthermore, mmu_circ_0015268 sponged miR-149 to upregulate the expression of its target Smad2. In summary, we demonstrated that has_circ_0003091 might be a novel target for the management and treatment of sepsis-induced ALI.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"44 1","pages":"5059 - 5074"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77206949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 5

CircSOX9 acts as a molecular sponge of miR-485-3p to promote the progression of nasopharyngeal carcinoma CircSOX9作为miR-485-3p的分子海绵，促进鼻咽癌的进展

Aging (Albany NY) Pub Date : 2022-06-14 DOI: 10.18632/aging.204127

Yan-bo Sun, Yun Liu, Zhi-hui Du, Liang-qiang Zhou, Qingguo Chen, Hanqi Chu

{"title":"CircSOX9 acts as a molecular sponge of miR-485-3p to promote the progression of nasopharyngeal carcinoma","authors":"Yan-bo Sun, Yun Liu, Zhi-hui Du, Liang-qiang Zhou, Qingguo Chen, Hanqi Chu","doi":"10.18632/aging.204127","DOIUrl":"https://doi.org/10.18632/aging.204127","url":null,"abstract":"Circular RNA (circRNA) plays a vital role in the occurrence and development of nasopharyngeal carcinoma (NPC). However, the role of certain specific circRNAs in NPC are still unknown. In this study, collect tumor samples and adjacent normal tissues from clinical NPC patients and detect the expression of circSOX9 by qRT-PCR. Use nucleoplasmic separation analysis, RNase R digestion assay and FISH to detect the characteristics of circSOX9. After knocking down circSOX9, clone formation experiment and transwell assay were used to detect the proliferation and invasion ability of nasopharyngeal carcinoma cells HONE1 and CNE2, and western blot was used to further detect the level of epithelial-mesenchymal transition (EMT). Use the database to screen for possible downstream target genes and verify them with dual-luciferase experiments. Bioinformatics analysis showed that circSOX9 was significantly up-regulated in NPC, and its expression level was positively correlated with the malignant progression of cancer. Data from function gain or loss studies showed that decrease of circSOX9 inhibited the invasion and proliferation of HONE1 and CNE2 cell lines. Further analysis proved that miR-485-3p was the downstream target of circSOX9. The luciferase test showed that by acting as a molecular sponge of miR-485-3p, circSOX9 promotes the proliferation and invasion of NPC cells, while miR-485-3p can target the expression of SOX9. In conclusion, circSOX9 acts as an oncogene in the progression of NPC through miR-485-3p/SOX9, indicating that circSOX9 can be used as a potential therapeutic target and predictive marker for nasopharyngeal carcinoma.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"19 1","pages":"4914 - 4926"},"PeriodicalIF":0.0,"publicationDate":"2022-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81215596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Correction for: ZNF139/circZNF139 promotes cell proliferation, migration and invasion via activation of PI3K/AKT pathway in bladder cancer ZNF139在膀胱癌中通过激活PI3K/AKT通路促进细胞增殖、迁移和侵袭

Aging (Albany NY) Pub Date : 2022-06-14 DOI: 10.18632/aging.204132

Jie Yao, Kaiyu Qian, Chen Chen, Xiao-ping Liu, Donghu Yu, Xin Yan, Tongzu Liu, Sheng Li

引用次数: 1

Effects of Qidantang Granule on early stage of diabetic kidney disease in rats 芪丹汤颗粒对大鼠早期糖尿病肾病的影响

Aging (Albany NY) Pub Date : 2022-06-13 DOI: 10.18632/aging.204121

Tengfei Wu, Xinyu Yang, Yilei Cong, Shisi Xia, Bowen Liu, Ran Zou, Juanhua Zeng, Hua Yang

引用次数: 3

An active ingredient isolated from Ganoderma lucidum promotes burn wound healing via TRPV1/SMAD signaling 从灵芝中分离出的一种活性成分通过TRPV1/SMAD信号通路促进烧伤创面愈合

Aging (Albany NY) Pub Date : 2022-06-13 DOI: 10.18632/aging.204119

C. Jiao, Hao Yun, Huijia Liang, Xiaodong Lian, Shunxian Li, Jiaming Chen, J. Qadir, Burton B. Yang, Yizhen Xie

{"title":"An active ingredient isolated from Ganoderma lucidum promotes burn wound healing via TRPV1/SMAD signaling","authors":"C. Jiao, Hao Yun, Huijia Liang, Xiaodong Lian, Shunxian Li, Jiaming Chen, J. Qadir, Burton B. Yang, Yizhen Xie","doi":"10.18632/aging.204119","DOIUrl":"https://doi.org/10.18632/aging.204119","url":null,"abstract":"The mushroom Ganoderma lucidum is a traditional Chinese medicine and G. lucidum spore oil (GLSO) is the lipid fraction isolated from Ganoderma spores. We examined the effect of GLSO on burn wound healing in mice. Following wounding, GLSO was applied on the wounds twice daily. Repair analysis was performed by Sirius-Red-staining at different time points. Cell proliferation and migration assays were performed to verify the effect of GLSO on growth. Network pharmacology analysis to identify possible targets was also carried out, followed by Western blotting, nuclear translocation, cell proliferation, and immunofluorescence assays for in-depth investigation of the mechanism. Our study showed that GLSO significantly promoted cell proliferation, and network pharmacology analysis suggested that GLSO might act through transient receptor potential vanilloid receptor 1 (TRPV1)/SMAD signaling. Furthermore, GLSO elevated SMAD2/3 expression in skin burn and promoted its nuclear translocation, and TRPV1 expression was also increased upon exposure to GLSO. Cell proliferation and immunofluorescence assays with TRPV1 inhibitor showed that GLSO accelerated skin burn wound healing through TRPV1 and SMADs signaling, which provides a foundation for clinical application of GLSO in the healing of deep skin burns.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"1 1","pages":"5376 - 5389"},"PeriodicalIF":0.0,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89901465","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 1

Effects of STAT3 on aging-dependent neovascularization impairment following limb ischemia: from bedside to bench STAT3对肢体缺血后衰老依赖性新生血管损伤的影响:从床边到实验室

Aging (Albany NY) Pub Date : 2022-06-13 DOI: 10.18632/aging.204122

W. Chang, You-Cheng Lin, C. Hong, Po-Sen Huang, Yu‐Wen Lin, Zhih-Cherng Chen, Tsung-Hsien Lin, T. Chao

{"title":"Effects of STAT3 on aging-dependent neovascularization impairment following limb ischemia: from bedside to bench","authors":"W. Chang, You-Cheng Lin, C. Hong, Po-Sen Huang, Yu‐Wen Lin, Zhih-Cherng Chen, Tsung-Hsien Lin, T. Chao","doi":"10.18632/aging.204122","DOIUrl":"https://doi.org/10.18632/aging.204122","url":null,"abstract":"Aging is a major risk factor for ischemic hypoxia-related diseases, including peripheral artery diseases (PADs). Signal transducer and activator of transcription 3 (STAT3) is a critical transcription activator in angiogenesis. Nevertheless, the effect of aging on endothelial cells and their responses to hypoxia are not well studied. Using a hindlimb hypoxic/ischemic model of aged mice, we found that aged mice (80-100-week-old) expressed significantly lower levels of angiogenesis than young mice (10-week-old). In our in vitro study, aged endothelial cells (≥30 passage) showed a significant accumulation of β-galactosidase and a high expression of aging-associated genes, including p16, p21, and hTERT compared with young cells (<10 passage). After 24 hours of hypoxia exposure, proliferation, migration and tube formation were significantly impaired in aged cells compared with young cells. Notably, STAT3 and angiogenesis-associated proteins such as PI3K/AKT were significantly downregulated in aged mouse limb tissues and aged cells. Further, using STAT3 siRNA, we found that suppressing STAT3 expression in endothelial cells impaired proliferation, migration and tube formation under hypoxia. Correspondingly, in patients with limb ischemia we also observed a higher expression of circulating STAT3, associated with a lower rate of major adverse limb events (MALEs). Collectively, STAT3 could be a biomarker reflecting the development of MALE in patients and also a regulator of age-dependent angiogenesis post limb ischemia. Additional studies are required to elucidate the clinical applications of STAT3.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"96 1","pages":"4897 - 4913"},"PeriodicalIF":0.0,"publicationDate":"2022-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"86047688","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3