Aging (Albany NY)最新文献_第8页

Epigenetic age and lung cancer risk in the CLUE II prospective cohort study CLUE II前瞻性队列研究中的表观遗传年龄与肺癌风险

Aging (Albany NY) Pub Date : 2022-05-22 DOI: 10.1101/2022.05.20.22275270

D. Michaud, M. Chung, N. Zhao, D. Koestler, Jiayun Lu, E. Platz, K. Kelsey

{"title":"Epigenetic age and lung cancer risk in the CLUE II prospective cohort study","authors":"D. Michaud, M. Chung, N. Zhao, D. Koestler, Jiayun Lu, E. Platz, K. Kelsey","doi":"10.1101/2022.05.20.22275270","DOIUrl":"https://doi.org/10.1101/2022.05.20.22275270","url":null,"abstract":"Background: Epigenetic age, a robust marker of biological aging, has been associated with obesity, low-grade inflammation and metabolic diseases. However, few studies have examined associations between different epigenetic age measures and risk of lung cancer, despite great interest in finding biomarkers to assist in risk stratification for lung cancer screening. Methods: A nested case-control study of lung cancer from the CLUE II cohort study was conducted using incidence density sampling with 1:1 matching of controls to lung cancer cases (n=208 matched pairs). Prediagnostic blood samples were collected in 1989 (CLUE II study baseline) and stored at -70 degrees Celsius. DNA was extracted from buffy coat and DNA methylation levels were measured using Illumina MethylationEPIC BeadChip Arrays. Three epigenetic age acceleration (i.e., biological age is greater than chronological age) measurements (Horvath, Hannum and PhenoAge) were examined in relation to lung cancer risk using conditional logistic regression. Results: We did not observe associations between the three epigenetic age acceleration measurements and risk of lung cancer overall; however, inverse associations for the two Hannum age acceleration measures (intrinsic and extrinsic) were observed in men and among younger participants, but not in women or older participants. We did not observe effect modification by time from blood draw to diagnosis. Conclusion: Findings from this study do not support a positive association between three different biological age acceleration measures and risk of lung cancer. Additional studies are needed to address whether epigenetic age is associated with lung cancer in never smokers.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"6 1","pages":"617 - 629"},"PeriodicalIF":0.0,"publicationDate":"2022-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75326287","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

Long noncoding RNA KCNQ1OT1 inhibits osteoclast differentiation by regulating the miR-128-3p/NFAT5 axis 长链非编码RNA kcnq10t1通过调节miR-128-3p/NFAT5轴抑制破骨细胞分化

Aging (Albany NY) Pub Date : 2022-05-19 DOI: 10.18632/aging.204088

Hengshuo Zhang, Lu Chen, Ziyu Wang, Zhen Sun, Yu Shan, Qinghui Li, Linzeng Qi, Hongliang Wang, Yunzhen Chen

{"title":"Long noncoding RNA KCNQ1OT1 inhibits osteoclast differentiation by regulating the miR-128-3p/NFAT5 axis","authors":"Hengshuo Zhang, Lu Chen, Ziyu Wang, Zhen Sun, Yu Shan, Qinghui Li, Linzeng Qi, Hongliang Wang, Yunzhen Chen","doi":"10.18632/aging.204088","DOIUrl":"https://doi.org/10.18632/aging.204088","url":null,"abstract":"Noncoding RNAs play an important role in regulating osteoclast differentiation. We investigated whether and how potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a long noncoding RNA, regulates osteoclast differentiation. We found that the expression of KCNQ1OT1 was downregulated in osteoporotic bone tissue. Then transfection of KCNQ1OT1 overexpression vectors or small interfering RNAs showed that the proliferation, migration, and osteoclast differentiation of RAW 264.7 cells were inhibited by KCNQ1OT1 upregulation, while they were promoted by KCNQ1OT1 knockdown. Interestingly, we found and confirmed that miR-128-3p was a target of KCNQ1OT1 using online databases, dual luciferase reporter assays and quantitative real-time polymerase chain reaction, and that it inhibited the expression of miR-128-3p. Moreover, we confirmed that miR-128-3p directly targeted nuclear factor of activated T cell 5 (NFAT5), a protein that combines with osteoprotegerin and thus regulates osteoclastogenesis with the presence of the receptor activator of nuclear factor κB ligand. Furthermore, we demonstrated that both the knockdown of KCNQ1OT1 and the overexpression of miR-128-3p attenuate the expression of NFAT5, while upregulating the osteoclastogenesis markers c-Fos, NFATc1, and Ctsk. The results from overexpression of KCNQ1OT1 and the inhibition of miR-128-3p were contrary to the above. Finally, we found that the inhibition of osteoclast differentiation by KCNQ1OT1 overexpression could be rescued using a miR-128-3p mimic, while the enhancement of migration and osteoclast differentiation by si-NFAT5 could be reversed with a miR-128-3p inhibitor. These results suggested that KCNQ1OT1 regulates the osteoclast differentiation via the miR-128-3p/NFAT5 axis.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"12 1","pages":"4486 - 4499"},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84848234","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

Combined impacts of histamine receptor H1 gene polymorphisms and an environmental carcinogen on the susceptibility to and progression of oral squamous cell carcinoma 组胺受体H1基因多态性与环境致癌物对口腔鳞状细胞癌易感性和进展的综合影响

Aging (Albany NY) Pub Date : 2022-05-19 DOI: 10.18632/aging.204089

Yi Ding, Yung‐Wei Lin, W. Chiu, Chiao-Wen Lin, Yi-Chieh Yang, L. Chang, Jungshan Chang, Shun-Fa Yang, M. Chien

{"title":"Combined impacts of histamine receptor H1 gene polymorphisms and an environmental carcinogen on the susceptibility to and progression of oral squamous cell carcinoma","authors":"Yi Ding, Yung‐Wei Lin, W. Chiu, Chiao-Wen Lin, Yi-Chieh Yang, L. Chang, Jungshan Chang, Shun-Fa Yang, M. Chien","doi":"10.18632/aging.204089","DOIUrl":"https://doi.org/10.18632/aging.204089","url":null,"abstract":"Oral squamous cell carcinoma (OSCC) is the most frequently encountered type of oral cancer. Histamine receptor H1 (HRH1) was reported to play a crucial role in OSCC carcinogenesis, but impacts of genetic variants of HRH1 on OSCC remain unclear. Herein, we investigated the association between functional single-nucleotide polymorphisms (SNPs) of HRH1 and OSCC susceptibility or clinicopathologic variables by logistic regression models. HRH1 genotypes at four loci (rs346074, rs346076, rs901865, and rs2606731) were analyzed by a TaqMan allelic discrimination assay, and we found that patients harboring HRH1 rs901865 T and rs346074 T alleles had a significantly lower risk of developing larger tumor sizes (>T2) under a dominant model. Based on the environmental carcinogen exposure status, we observed that HRH1 rs901865 polymorphic variants were also associated with a lower risk of developing more-advanced clinical stages (III or IV) in patients with a betel-quid-chewing habit. Moreover, genotype screening of rs901865 and rs346074 in OSCC cell lines showed that cells respectively carrying the CT and TT genotypes expressed lower HRH1 levels compared to cells carrying the CC genotype of rs901865 and rs346074. Furthermore, analyses of TCGA and GEO databases revealed that HRH1 expression levels were upregulated in head and neck squamous cell carcinoma (HNSCC) and OSCC tissues compared to normal tissues and were correlated with larger tumor sizes and poorer prognoses. These results indicated the involvement of HRH1 SNPs rs901865 and rs346074 in OSCC development and support the interaction between HRH1 gene polymorphisms and an environmental carcinogen as a predisposing factor for OSCC progression.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"24 1","pages":"4500 - 4512"},"PeriodicalIF":0.0,"publicationDate":"2022-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78577426","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

Molecular markers associated with cognitive impairment in centenarians 与百岁老人认知障碍相关的分子标记

Aging (Albany NY) Pub Date : 2022-05-18 DOI: 10.18632/aging.204094

T. Stevnsner, Inés Sánchez-Román

{"title":"Molecular markers associated with cognitive impairment in centenarians","authors":"T. Stevnsner, Inés Sánchez-Román","doi":"10.18632/aging.204094","DOIUrl":"https://doi.org/10.18632/aging.204094","url":null,"abstract":"degenerative diseases. Therefore, unravelling the basic mechanisms of aging is essential to improve the quality of life of older people. Among others, mitochondrial dysfunction and genomic instability have been considered key hallmarks of aging, and these deficiencies seem to play important roles in age associated cognitive decline [1]. Mitochondrial bioenergetic deterioration together with reactive oxygen species (ROS) induced mitochondrial DNA damage have been shown to accumulate with aging [2]. DNA repair pathways, which are involved in maintaining genomic stability, also seem to change with aging. Most oxidative DNA lesions are repaired by the Base Excision Repair (BER) pathway, in which the major endonuclease at the limiting step is AP endonuclease 1 (APE1), which has also been linked to cognitive decline [3]. Mitochondrial function and DNA repair activity are affected by nicotinamide adenine dinucleotide (NAD) depletion, which is also observed with aging. NAD is an essential co-enzyme involved in mitochondrial health and functions as a cofactor for the DNA repair protein poly (ADP-ribose) polymerase 1 (PARP-1) [4]. Another factor that has been shown to decline with aging and be reduced in neurodegenerative diseases is brain derived neurotrophic factor (BDNF). Importantly, BDNF has been shown to enhance neuronal DNA repair by stimulating APE1 expression and activity [5].","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"7 1","pages":"4191 - 4192"},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"82716550","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

NcRNAs-mediated P2RX1 expression correlates with clinical outcomes and immune infiltration in patients with breast invasive carcinoma ncrnas介导的P2RX1表达与乳腺浸润性癌患者的临床结局和免疫浸润相关

Aging (Albany NY) Pub Date : 2022-05-18 DOI: 10.18632/aging.204087

Yiyue Xu, B. Zou, B. Fan, Butuo Li, Jinming Yu, Linlin Wang, Jin Zhang

引用次数: 2

Are beta blockers effective in preventing stroke-associated infections? - a systematic review and meta-analysis 受体阻滞剂对预防卒中相关感染有效吗?-系统回顾和荟萃分析

Aging (Albany NY) Pub Date : 2022-05-18 DOI: 10.18632/aging.204086

Li Yang, Wen-ping Xiang, Jinfeng Zhang, Jiangxia Pang, Jingbo Wang, Baojun Wang

{"title":"Are beta blockers effective in preventing stroke-associated infections? - a systematic review and meta-analysis","authors":"Li Yang, Wen-ping Xiang, Jinfeng Zhang, Jiangxia Pang, Jingbo Wang, Baojun Wang","doi":"10.18632/aging.204086","DOIUrl":"https://doi.org/10.18632/aging.204086","url":null,"abstract":"Background: Excessive sympathoexcitation could lead to stroke associated infection. Inhibiting sympathetic excitation may reduce the infection risk after stroke. Thus, the present study aimed to determine the protective effect of beta blockers on stroke associated infection through systematic review and meta-analysis. Methods: A systematic search of multiple databases were performed up to February 2022. The included studies required beta blockers therapy in stroke patients and assessed the incidence of stroke-associated infections. Outcomes of interest included infections, pneumonia, urinary tract infection and sepsis. Random-effects model was used for analysis. Heterogeneity was evaluated using I2 statistics and publication bias was evaluated by the funnel plot. Result: A total of 83 potentially relevant publications was identified in the initial search. Six studies met the inclusion criteria for meta-analysis. The risk of bias in the included articles satisfies the quality requirement of meta-analysis. No significant associations between beta blockers therapy and the prevention of stroke associated infection, stroke associated pneumonia and septicemia were found, However, subgroup analyses revealed an association between beta blockers treatment and the increased risk of post-stroke urinary tract infection or stroke associated pneumonia in some stroke patients (OR = 1.69 [1.33, 2.14], P < 0.0001; OR = 1.85 [1.51, 2.26], P < 0.0001). Conclusion: Due to the lack of robust evidence, this meta-analysis may not support the preventive effect of beta blockers on stroke associated infection. But beta blockers treatment may be associated with development of post-stroke urinary tract infection and stroke associated pneumonia in some stroke patients.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"104 1","pages":"4459 - 4470"},"PeriodicalIF":0.0,"publicationDate":"2022-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"77381438","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

Intra-tumoral angiogenesis correlates with immune features and prognosis in glioma 胶质瘤的肿瘤内血管生成与免疫特征和预后相关

Aging (Albany NY) Pub Date : 2022-05-17 DOI: 10.18632/aging.204079

Qing Zhang, Yao Guo, Wan-Lin Zhang, H. Lian, Natasha Iranzad, Endi Wang, Ying-Chun Li, Hai Tong, Le-Yao Li, Ling-Yun Dong, Lian-He Yang, Shuang Ma

引用次数: 0

Identification of combined biomarkers for predicting the risk of osteoporosis using machine learning 利用机器学习识别预测骨质疏松风险的联合生物标志物

Aging (Albany NY) Pub Date : 2022-05-17 DOI: 10.18632/aging.204084

Zhenlong Zheng, Xianglan Zhang, Bong-Kyeong Oh, Ki-Yeol Kim

{"title":"Identification of combined biomarkers for predicting the risk of osteoporosis using machine learning","authors":"Zhenlong Zheng, Xianglan Zhang, Bong-Kyeong Oh, Ki-Yeol Kim","doi":"10.18632/aging.204084","DOIUrl":"https://doi.org/10.18632/aging.204084","url":null,"abstract":"Osteoporosis is a severe chronic skeletal disorder that affects older individuals, especially postmenopausal women. However, molecular biomarkers for predicting the risk of osteoporosis are not well characterized. The aim of this study was to identify combined biomarkers for predicting the risk of osteoporosis using machine learning methods. We merged three publicly available gene expression datasets (GSE56815, GSE13850, and GSE2208) to obtain expression data for 6354 unique genes in postmenopausal women (45 with high bone mineral density and 45 with low bone mineral density). All machine learning methods were implemented in R, with the GEOquery and limma packages, for dataset download and differentially expressed gene identification, and a nomogram for predicting the risk of osteoporosis was constructed. We detected 378 significant differentially expressed genes using the limma package, representing 15 major biological pathways. The performance of the predictive models based on combined biomarkers (two or three genes) was superior to that of models based on a single gene. The best predictive gene set among two-gene sets included PLA2G2A and WRAP73. The best predictive gene set among three-gene sets included LPN1, PFDN6, and DOHH. Overall, we demonstrated the advantages of using combined versus single biomarkers for predicting the risk of osteoporosis. Further, the predictive nomogram constructed using combined biomarkers could be used by clinicians to identify high-risk individuals and in the design of efficient clinical trials to reduce the incidence of osteoporosis.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"107 1","pages":"4270 - 4280"},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81470323","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

Sperm DNA integrity is critically impacted by male age but does not influence outcomes of artificial insemination by husband in the Chinese infertile couples 在中国不育夫妇中，精子DNA完整性受到男性年龄的严重影响，但不影响丈夫人工授精的结果

Aging (Albany NY) Pub Date : 2022-05-17 DOI: 10.18632/aging.204058

Yumei Luo, Shunhong Wu, Mimi Zhang, Hua Zhou, Jingru Yuan, Yiying Yang, Yufang Zhong, Qing Li, Xiaofang Sun, Xia Xu, Detu Zhu

{"title":"Sperm DNA integrity is critically impacted by male age but does not influence outcomes of artificial insemination by husband in the Chinese infertile couples","authors":"Yumei Luo, Shunhong Wu, Mimi Zhang, Hua Zhou, Jingru Yuan, Yiying Yang, Yufang Zhong, Qing Li, Xiaofang Sun, Xia Xu, Detu Zhu","doi":"10.18632/aging.204058","DOIUrl":"https://doi.org/10.18632/aging.204058","url":null,"abstract":"The sperm chromatin structure assay (SCSA) is crucial for assessing male fertility. However, the predictive value of the SCSA parameters, including the DNA fragment indices (DFI) and the percentages of high DNA stainability (HDS), for outcomes of artificial insemination by husband (AIH) remains controversial. This study aims to evaluate the correlations between SCSA parameters and male aging as well as other routine semen parameters, and explore their prognostic powers on AIH outcomes of the Chinese infertile couples. A total of 809 AIH cycles were retrospectively analyzed. The results showed that DFI in the age groups < 35 years were significantly lower than that in the age groups ≥ 35 years (P < 0.001). Meanwhile, there was no statistical difference in HDS between the age groups (P = 0.063). DFI and HDS are negatively correlated with most routine semen parameters (all P < 0.05). The chi-square and generalized linear model tests indicated that neither DFI nor HDS influenced the clinical pregnancy rate of AIH. In summary, this study found that aging is a critical factor leading to increased sperm DFI but not HDS. DFI and HDS are negatively correlated with most semen parameters but do not significantly influence AIH outcomes.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"121 1","pages":"4326 - 4335"},"PeriodicalIF":0.0,"publicationDate":"2022-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76706211","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: 7

Senescence-associated morphological profiles (SAMPs): an image-based phenotypic profiling method for evaluating the inter and intra model heterogeneity of senescence 衰老相关形态学特征(SAMPs):一种基于图像的表型分析方法，用于评估衰老的模型间和模型内异质性

Aging (Albany NY) Pub Date : 2022-05-16 DOI: 10.18632/aging.204072

Ryan Wallis, Deborah A. Milligan, Bethany K Hughes, Hannah Mizen, J. López-Domínguez, Ugochim Eduputa, E. Tyler, M. Serrano, C. Bishop

{"title":"Senescence-associated morphological profiles (SAMPs): an image-based phenotypic profiling method for evaluating the inter and intra model heterogeneity of senescence","authors":"Ryan Wallis, Deborah A. Milligan, Bethany K Hughes, Hannah Mizen, J. López-Domínguez, Ugochim Eduputa, E. Tyler, M. Serrano, C. Bishop","doi":"10.18632/aging.204072","DOIUrl":"https://doi.org/10.18632/aging.204072","url":null,"abstract":"Senescence occurs in response to a number of damaging stimuli to limit oncogenic transformation and cancer development. As no single, universal senescence marker has been discovered, the confident classification of senescence induction requires the parallel assessment of a series of hallmarks. Therefore, there is a growing need for “first-pass” tools of senescence identification to streamline experimental workflows and complement conventional markers. Here, we utilise a high content, multidimensional phenotypic profiling-based approach, to assess the morphological profiles of senescent cells induced via a range of stimuli. In the context of senescence, we refer to these as senescence-associated morphological profiles (SAMPs), as they facilitate distinction between senescent and proliferating cells. The complexity of the profiles generated also allows exploration of the heterogeneity both between models of senescence and within an individual senescence model, providing a level of insight at the single cell level. Furthermore, we also demonstrate that these models are applicable to the assessment of senescence in vivo, which remains a key challenge for the field. Therefore, we believe SAMPs has the potential to serve as a useful addition in the repertoire of senescence researchers, either as a first-pass tool or as part of the established senescence hallmarks.","PeriodicalId":7669,"journal":{"name":"Aging (Albany NY)","volume":"89 1","pages":"4220 - 4246"},"PeriodicalIF":0.0,"publicationDate":"2022-05-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83868106","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: 9