Aging (Albany NY)最新文献_第7页

The bioinformatics and experimental analysis of the novel roles of virus infection-associated gene CDC20 for prognosis and immune infiltration in hepatocellular carcinoma 病毒感染相关基因CDC20在肝癌预后和免疫浸润中的新作用的生物信息学和实验分析

Aging (Albany NY) Pub Date : 2022-05-27 DOI: 10.18632/aging.204093

Juanni Li, Xiaofang Zhang, Lei Yao, K. Hu

{"title":"The bioinformatics and experimental analysis of the novel roles of virus infection-associated gene CDC20 for prognosis and immune infiltration in hepatocellular carcinoma","authors":"Juanni Li, Xiaofang Zhang, Lei Yao, K. Hu","doi":"10.18632/aging.204093","DOIUrl":"https://doi.org/10.18632/aging.204093","url":null,"abstract":"Infection virus including HBV and HCV has been well recognized as a major cause inducing hepatocellular carcinoma (HCC). However, molecular investigations into the HTLV-1 (Human T-lymphotropic virus type-1) and HCC have been rare. In this study, we integrated several public datasets of HCC patients and filtered seven genes including CDC20 as the HTLV-1 infection-related genes which were differentially expressed in HCC. CDC20 was chosen for further investigation based on its promising prognostic power. The expression profiles, prognostic assessment, association with clinicopathologic characteristics, prediction of correlated signal pathways, and the immune-modulating function of CDC20 were assessed. We found that CDC20 expression was significantly increased in hepatocellular carcinoma tissues and cell lines, and was correlated with histologic grade, pathologic stage, tumor status, and patient age. CDC20 exhibited prognostic value on overall survival and disease specific survival and was an independent prognostic factor. It was primarily involved in several signal pathways, especially the omega-hydroxylase P450 and epoxygenase P450 signal pathways. Moreover, CDC20 expression showed significant positive associations with the levels of several immune cells such as T helper 2 cells and follicular helper T cells, immunostimulators including TNFRSF18 and MICB, immunoinhibitors including KDR and PDCD1LG2, chemokines including XCL1 and CCL26, and chemokine receptors including CCR10 and CXCR3. This study for the first time delineated the correlation of CDC20 with HTLV-1 infection-associated HCC. The disorder of expression and function of CDC20 makes it a probable biomarker for better etiological classification, prognostic prediction, and precision medicine.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"27 1","pages":"4513 - 4529"},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78829026","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

HIV-Tat protein-accelerated aging HIV-Tat蛋白加速衰老

Aging (Albany NY) Pub Date : 2022-05-27 DOI: 10.18632/aging.204105

M. Kaufman, Alaa N. Qrareya, J. Paris

{"title":"HIV-Tat protein-accelerated aging","authors":"M. Kaufman, Alaa N. Qrareya, J. Paris","doi":"10.18632/aging.204105","DOIUrl":"https://doi.org/10.18632/aging.204105","url":null,"abstract":"accelerates aging [1]. This effect is expected to become increasingly problematic because currently, in the United States, more than half of those infected with HIV are over 50 years old and thus are subjected to the combined effects of HIV and aging [1]. Antiretroviral therapy (ART) for HIV greatly suppresses viral loads and reduces HIV-related morbidity and mortality, enabling people living with HIV (PLWH) to have a much better quality-of-life and survive into old age. However, ART does not prevent neurological disturbances from developing in PLWH including disruptions in mood and cognitive ability and the development of intractable pain states. These comorbidities reduce quality-of-life and catalyze problematic behaviors including substance use disorders that worsen HIVand age-related outcomes. These sequelae occur in part because ART does not stop HIV reservoirs from synthesizing and releasing toxic proteins such as the transactivator of transcription (Tat) protein, appreciable levels of which are present in the central nervous system during ART (e.g., [2]). In particular, Tat is neurotoxic and it induces neuroinflammation, oxidative stress, and mitochondrial dysfunction (see [3]), effects that also are associated with aging [1].","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"37 1","pages":"4618 - 4619"},"PeriodicalIF":0.0,"publicationDate":"2022-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80610856","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

Comprehensive analysis of expression profiles and prognosis of TRIM genes in human kidney clear cell carcinoma TRIM基因在人肾透明细胞癌中的表达谱及预后综合分析

Aging (Albany NY) Pub Date : 2022-05-26 DOI: 10.18632/aging.204102

Junwen Shen, Rong-jiang Wang, Yu Chen, Zhihai Fang, Jian-er Tang, Jianxiang Yao, Jian-guo Gao, Wenxia Zhou, Xiongnong Chen

{"title":"Comprehensive analysis of expression profiles and prognosis of TRIM genes in human kidney clear cell carcinoma","authors":"Junwen Shen, Rong-jiang Wang, Yu Chen, Zhihai Fang, Jian-er Tang, Jianxiang Yao, Jian-guo Gao, Wenxia Zhou, Xiongnong Chen","doi":"10.18632/aging.204102","DOIUrl":"https://doi.org/10.18632/aging.204102","url":null,"abstract":"Objective: To determine survival rates and the underlying mechanism of genes in the TRIM family in Kidney Clear Cell Carcinoma (KIRC). Methods: Transcriptional and survival data of TRIM genes in KIRC patients were retrieved from the UCSC Xena, and GEPIA databases. The function of TRIM genes in KIRC was investigated, focusing on potential ubiquitination, miRNAs regulation, and enrichment analysis. Next, TRIM gene survival values were determined, followed by the development of a survival-related signature. Results: Only TRIM26 was down expressed in the carcinoma tissue and had a survival value in KIRC relative to control tissues, which was supplied by vitro experiment. The patients with lower expression of TRIM26 would have the chance to live a shorter time. SNRPB, which also plays a role in ubiquitination, directly interacted with TRIM26. Moreover, two miRNAs (hsa-let-7i-5p, and hsa-miR-1228-5p) that regulated levels of TRIM26 expression were also identified. Next, we constructed a signature (TRIM4/7/27/58/65/72) and found that high-risk scores of the signature were associated with poor survival rates in KIRC patients. while its resultant risk scores were correlated with immune cell components and markers. Conclusions: TRIM26 was differentially expressed between KIRC and normal tissues and had a survival value in the KIRC. hsa-let-7i-5p/hsa-miR-1228-5p-TRIM26-SNRPB was a potential mechanism axis that may play a role on the KIRC cells. A survival signature (TRIM4/7/27/58/65/72) was successfully established to predict the survival of KIRC patients.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"22 1","pages":"4606 - 4617"},"PeriodicalIF":0.0,"publicationDate":"2022-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82281324","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: 2

The impact of ALDH7A1 variants in oral cancer development and prognosis ALDH7A1变异对口腔癌发展和预后的影响

Aging (Albany NY) Pub Date : 2022-05-25 DOI: 10.18632/aging.204099

Hsueh-Ju Lu, C. Chuang, Mu-Kuan Chen, Chun-Wen Su, Wei‐En Yang, Chia-Ming Yeh, K. Lai, Chih-Hsin Tang, Chiao-Wen Lin, Shun-Fa Yang

{"title":"The impact of ALDH7A1 variants in oral cancer development and prognosis","authors":"Hsueh-Ju Lu, C. Chuang, Mu-Kuan Chen, Chun-Wen Su, Wei‐En Yang, Chia-Ming Yeh, K. Lai, Chih-Hsin Tang, Chiao-Wen Lin, Shun-Fa Yang","doi":"10.18632/aging.204099","DOIUrl":"https://doi.org/10.18632/aging.204099","url":null,"abstract":"The gene encoding aldehyde dehydrogenase 7 family member A1 (ALDH7A1) has been associated with the development and prognosis in multiple cancers; however, the role of ALDH7A1 polymorphisms in oral cancer remains unknown. For this purpose, the influences of ALDH7A1 rs13182402 and rs12659017 on oral cancer development and prognosis were analyzed. Our resulted showed that ALDH7A1 rs13182402 genotype had less pathologic nodal metastasis among betel quid chewer. ALDH7A1 rs13182402 also corresponded to higher expressions in upper aerodigestive mucosa, whole blood, the musculoskeletal system and oral cancer tissues than did the ALDH7A1 wild type. Furthermore, ALDH7A1 overexpression in oral cancer cells increased in vitro migration, whereas its silencing reduced cell migration. Conversely, ALDH7A1 expression in tumor tissues and in patients with advanced disease was lower than that in normal tissues and in patients with early-stage disease. When the patients were classified into ALDH7A1-high and -low-expression groups, the high-ALDH7A1 group had superior outcomes in progression-free survival than the low-ALDH7A1 group (5-year survival of 58.7% vs. 48.0%, P = 0.048) did. In conclusion, patients with high ALDH7A1 expression might, however, have more favorable prognoses than those with low ALDH7A1 expression have.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"5 1","pages":"4556 - 4571"},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83154294","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

Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis 乳转铁蛋白通过调节Fas和抑制人髓核细胞凋亡促进椎间盘退变

Aging (Albany NY) Pub Date : 2022-05-25 DOI: 10.18632/aging.204100

Xiao-Bo Zhang, Si-Qi Xu, Yi-Geng Hui, Hai-Yu Zhou, Yi-cun Hu, Rui-hao Zhang, Xi-dan Gao, Chang-Ming Zheng

{"title":"Lactotransferrin promotes intervertebral disc degeneration by regulating Fas and inhibiting human nucleus pulposus cell apoptosis","authors":"Xiao-Bo Zhang, Si-Qi Xu, Yi-Geng Hui, Hai-Yu Zhou, Yi-cun Hu, Rui-hao Zhang, Xi-dan Gao, Chang-Ming Zheng","doi":"10.18632/aging.204100","DOIUrl":"https://doi.org/10.18632/aging.204100","url":null,"abstract":"Background: In recent years, intervertebral disc (IVD) degeneration (IDD) has increased in age. There is still a lack of effective treatment in clinics, which cannot improve the condition of IDD at the level of etiology. Objective: To explore IDD pathogenesis at the cellular and gene levels and investigate lactotransferrin (LTF) expression in IDD patients and its possible mechanism. Methods: We downloaded the IDD data set from the Gene Expression Omnibus (GEO) database, screened the differentially expressed genes (DEGs) and hub genes and performed Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis to construct a protein–protein interaction (PPI) network. Subsequently, we verified LTF's regulatory mechanism through cell experiments. IL-1β was used to intervene in nucleus pulposus cells (NPCs) to construct the IDD cell model, and LTF and Fas expression was detected by qRT–PCR. LTF inhibitor, Fas inhibitor, LTF mimic, and Fas mimic were used to intervene in each group. Western blotting was used to detect Fas, Caspase-3, Bax, and Bcl-2 expression. Results: A total of 131 DEGs and 10 hub genes were screened. LTF mRNA in the IDD model was significantly higher than that in the control group, while Fas' mRNA was significantly lower. When LTF was upregulated or downregulated in NPCs, apoptosis marker expression showed the opposite trend. The rescue test showed that LTF and Fas' overexpression greatly enhanced NPC apoptosis. Conclusion: LTF promotes IDD progression by regulating Fas in NPCs, and it may be an effective gene therapy target.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"14 1","pages":"4572 - 4585"},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87522600","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

Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis 多发性肌炎和皮肌炎中心生物标志物和免疫细胞浸润的鉴定

Aging (Albany NY) Pub Date : 2022-05-24 DOI: 10.18632/aging.204098

Si Chen, Haolong Li, H. Zhan, Xiaoli Zeng, Hui Yuan, Yongzhe Li

{"title":"Identification of hub biomarkers and immune cell infiltration in polymyositis and dermatomyositis","authors":"Si Chen, Haolong Li, H. Zhan, Xiaoli Zeng, Hui Yuan, Yongzhe Li","doi":"10.18632/aging.204098","DOIUrl":"https://doi.org/10.18632/aging.204098","url":null,"abstract":"Objective: Polymyositis (PM) and dermatomyositis (DM) are heterogeneous disorders. However, the etiology of PM/DM development has not been thoroughly clarified. Methods: Gene expression data of PM/DM were obtained from Gene Expression Omnibus. We used robust rank aggregation (RRA) to identify differentially expressed genes (DEGs). Gene Ontology functional enrichment and pathway analyses were used to investigate potential functions of the DEGs. Weighted gene co-expression network analysis (WGCNA) was used to establish a gene co-expression network. CIBERSORT was utilized to analyze the pattern of immune cell infiltration in PM/DM. Protein–protein interaction (PPI) network, Venn, and association analyses between core genes and muscle injury were performed to identify hub genes. Receiver operating characteristic analyses were executed to investigate the value of hub genes in the diagnosis of PM/DM, and the results were verified using the microarray dataset GSE48280. Results: Five datasets were included. The RRA integrated analysis identified 82 significant DEGs. Functional enrichment analysis revealed that immune function and the interferon signaling pathway were enriched in PM/DM. WGCNA outcomes identified MEblue and MEturquoise as key target modules in PM/DM. Immune cell infiltration analysis revealed greater macrophage infiltration and lower regulatory T-cell infiltration in PM/DM patients than in healthy controls. PPI network, Venn, and association analyses of muscle injury identified five putative hub genes: TRIM22, IFI6, IFITM1, IFI35, and IRF9. Conclusions: Our bioinformatics analysis identified new genetic biomarkers of the pathogenesis of PM/DM. We demonstrated that immune cell infiltration plays a pivotal part in the occurrence of PM/DM.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"6 1","pages":"4530 - 4555"},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90292201","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: 4

Identification and validation of aging-related genes in COPD based on bioinformatics analysis 基于生物信息学分析的COPD衰老相关基因的鉴定和验证

Aging (Albany NY) Pub Date : 2022-05-24 DOI: 10.18632/aging.204064

Shan Zhong, Li Yang, Naijia Liu, Guangkeng Zhou, Zhangli Hu, Chengshui Chen, Yun Wang

{"title":"Identification and validation of aging-related genes in COPD based on bioinformatics analysis","authors":"Shan Zhong, Li Yang, Naijia Liu, Guangkeng Zhou, Zhangli Hu, Chengshui Chen, Yun Wang","doi":"10.18632/aging.204064","DOIUrl":"https://doi.org/10.18632/aging.204064","url":null,"abstract":"Chronic obstructive pulmonary disease (COPD) is a serious chronic respiratory disorder. One of the major risk factors for COPD progression is aging. Therefore, we investigated aging-related genes in COPD using bioinformatic analyses. Firstly, the Aging Atlas database containing 500 aging-related genes and the Gene Expression Omnibus database (GSE38974) were utilized to screen candidates. A total of 24 candidate genes were identified related to both COPD and aging. Using gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, we found that this list of 24 genes was enriched in genes associated with cytokine activity, cell apoptosis, NF-κB and IL-17 signaling. Four of these genes (CDKN1A, HIF1A, MXD1 and SOD2) were determined to be significantly upregulated in clinical COPD samples and in cigarette smoke extract-exposed Beas-2B cells in vitro, and their expression was negatively correlated with predicted forced expiratory volume and forced vital capacity. In addition, the combination of expression levels of these four genes had a good discriminative ability for COPD patients (AUC = 0.794, 95% CI 0.743–0.845). All four were identified as target genes of hsa-miR-519d-3p, which was significantly down-regulated in COPD patients. The results from this study proposed that regulatory network of hsa-miR-519d-3p/CDKN1A, HIF1A, MXD1, and SOD2 closely associated with the progression of COPD, which provides a theoretical basis to link aging effectors with COPD progression, and may suggest new diagnostic and therapeutic targets of this disease.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"3 1","pages":"4336 - 4356"},"PeriodicalIF":0.0,"publicationDate":"2022-05-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"88200242","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

Exercise intervention prevents early aged hypertension-caused cardiac dysfunction through inhibition of cardiac fibrosis 运动干预通过抑制心脏纤维化预防早衰高血压引起的心功能障碍

Aging (Albany NY) Pub Date : 2022-05-23 DOI: 10.18632/aging.204077

Yi Hong, A. Yang, James K. S. Wong, Kunanya Masodsai, Shin-Da Lee, Yi-Yuan Lin

{"title":"Exercise intervention prevents early aged hypertension-caused cardiac dysfunction through inhibition of cardiac fibrosis","authors":"Yi Hong, A. Yang, James K. S. Wong, Kunanya Masodsai, Shin-Da Lee, Yi-Yuan Lin","doi":"10.18632/aging.204077","DOIUrl":"https://doi.org/10.18632/aging.204077","url":null,"abstract":"Background: An inappropriate accumulation of fibrillar collagen is a common pathologic feature of early aged hypertensive heart disease, but little information regarding the effects of exercise training on cardiac fibrosis in hypertension is available. The purpose of this study was to evaluate the effects of exercise training on cardiac fibrotic pathways in early aged hypertensive rats. Methods: Masson’s trichrome staining and Western blotting were performed on the excised left ventricle from twenty male spontaneously hypertensive rats at age of 48 weeks, which were randomly divided into either a sedentary hypertensive group (SHR) or exercise hypertensive group (SHR-EX, running on a treadmill running occurred 5 days/week for 60 min/day, for 12 weeks), and from age-matched male Wistar–Kyoto normotensive controls (WKY). Results: Interstitial fibrosis was reduced in the SHR-Ex group when compared with the SHR group. The fibrotic-related protein levels of AT1R, FGF23, LOX-2, TGF-β, CTGF, p-Smad 2/3, MMP-2/TIMP-2, MMP-9/TIMP-1, uPA and collagen I were decreased in the SHR-EX group, when compared with the SHR group. Conclusions: Exercise training suppresses early aged hypertensive heart-induced LOX-2/TGF-β-mediated fibrotic pathways associated with decreasing AT1R and FGF23, which might provide a new therapeutic effect for exercise training to prevent adverse cardiac fibrosis and myocardial abnormalities in early aged hypertension.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"14 1","pages":"4390 - 4401"},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73281801","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

Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism 长期服用氯喹可以延长中年雄性小鼠的寿命，可能是通过调节自噬、抑制蛋白酶体和糖原代谢来实现的

Aging (Albany NY) Pub Date : 2022-05-23 DOI: 10.18632/aging.204069

T. Doeppner, C. Coman, Daiana Burdusel, D. Ancuta, U. Brockmeier, D. Pirici, Y. Kuang, D. Hermann, A. Popa-Wagner

{"title":"Long-term treatment with chloroquine increases lifespan in middle-aged male mice possibly via autophagy modulation, proteasome inhibition and glycogen metabolism","authors":"T. Doeppner, C. Coman, Daiana Burdusel, D. Ancuta, U. Brockmeier, D. Pirici, Y. Kuang, D. Hermann, A. Popa-Wagner","doi":"10.18632/aging.204069","DOIUrl":"https://doi.org/10.18632/aging.204069","url":null,"abstract":"Previous studies have shown that the polyamine spermidine increased the maximum life span in C. elegans and the median life span in mice. Since spermidine increases autophagy, we asked if treatment with chloroquine, an inhibitor of autophagy, would shorten the lifespan of mice. Recently, chloroquine has intensively been discussed as a treatment option for COVID-19 patients. To rule out unfavorable long-term effects on longevity, we examined the effect of chronic treatment with chloroquine given in the drinking water on the lifespan and organ pathology of male middle-aged NMRI mice. We report that, surprisingly, daily treatment with chloroquine extended the median life span by 11.4% and the maximum life span of the middle-aged male NMRI mice by 11.8%. Subsequent experiments show that the chloroquine-induced lifespan elevation is associated with dose-dependent increase in LC3B-II, a marker of autophagosomes, in the liver and heart that was confirmed by transmission electron microscopy. Quite intriguingly, chloroquine treatment was also associated with a decrease in glycogenolysis in the liver suggesting a compensatory mechanism to provide energy to the cell. Accumulation of autophagosomes was paralleled by an inhibition of proteasome-dependent proteolysis in the liver and the heart as well as with decreased serum levels of insulin growth factor binding protein-3 (IGFBP3), a protein associated with longevity. We propose that inhibition of proteasome activity in conjunction with an increased number of autophagosomes and decreased levels of IGFBP3 might play a central role in lifespan extension by chloroquine in male NMRI mice.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"5 1","pages":"4195 - 4210"},"PeriodicalIF":0.0,"publicationDate":"2022-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"90178294","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

Glioblastoma: two immune subtypes under the surface of the cold tumor 胶质母细胞瘤:冷瘤表面下的两种免疫亚型

Aging (Albany NY) Pub Date : 2022-05-23 DOI: 10.18632/aging.204067

Wu Xiong, Cong Li, G. Kong, B. Wan, Siming Wang, Jin Fan

引用次数: 1