Aging-Us最新文献

{"title":"Correction for: miR-926-3p influences myocardial injury in septic mice through regulation of mTOR signaling pathway by targeting TSC1.","authors":"Feng Yan, Qian Wang, Huiyu Yang, Hui Lv, Weiwei Qin","doi":"10.18632/aging.206127","DOIUrl":"https://doi.org/10.18632/aging.206127","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333055","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction of: Sulfated polysaccharide of <i>Sepiella maindroni</i> ink targets Akt and overcomes resistance to the FGFR inhibitor AZD4547 in bladder cancer.","authors":"Liping Shan, Wei Liu, Yunhong Zhan","doi":"10.18632/aging.206104","DOIUrl":"https://doi.org/10.18632/aging.206104","url":null,"abstract":"","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Use of the senolytics dasatinib and quercetin for prevention of pelvic organ prolapse in a mouse animal model.","authors":"Erryn Tappy, Haolin Shi, Jessica Pruszynski, Maria Florian-Rodriguez","doi":"10.18632/aging.206120","DOIUrl":"https://doi.org/10.18632/aging.206120","url":null,"abstract":"<p><strong>Objective: </strong>Senolytic agents have the potential to target age-related pathology associated with cellular senescence and reduce senescent cell activity in several disease processes. We utilized a mouse model of pelvic organ prolapse, Fibulin-5 knockout (<i>Fbln-5^-/-)</i> mice, to assess the ability of dasatinib and quercetin (D+Q) to prevent development of prolapse.</p><p><strong>Methods: </strong>Four-week-old female <i>Fbln-5^-/-</i> (n=63) and wild-type (WT) mice (n=54) were assigned to control (vehicle injection) or treatment (D = 5 mg/kg, Q = 50 mg/kg) groups. Weekly oral gavage injections were administered from weeks 4-8 of life. Pelvic organ prolapse quantification system measurements were obtained weekly. Vaginal tissue was harvested at 10, 12 and 20 weeks. Tissue analysis included immunostaining for cell cycle inhibitors, multiplex cytokine analysis, senescence-associated-β-galactosidase (SA-β-Gal) and histologic analysis of extracellular matrix proteins.</p><p><strong>Results: </strong>Perineal body length was significantly longer in <i>Fbln-5^-/-</i> treatment mice at 20 weeks. Expression of p16 and p53 was decreased in <i>Fbln-5^-/-</i> treatment mice compared to controls (4.0% vs. 26.7%, p=0.0124 and 2.9% vs. 16.8%, p=0.272) at 20 weeks. Expression of SA-β-Gal and senescence-associated cytokines did not vary significantly between groups. At 20 weeks, vaginal tissue elastin content in <i>Fbln-5^-/-</i> treatment mice increased compared to controls (1.04% vs. 0.84%, p=0.999).</p><p><strong>Conclusions: </strong>D+Q injections did not result in clinically significant differences in prolapse development but did demonstrate decreased expression of cellular senescence markers in <i>Fbln-5^-/-</i> mice. This suggests senolytic agents may mitigate contributions of cellular senescence to tissue dysfunction associated with prolapse. Further studies are needed to confirm ideal timing, dosage, and route of senolytics in prevention of prolapse.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333054","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Revealing a cancer-associated fibroblast-based risk signature for pancreatic adenocarcinoma through single-cell and bulk RNA-seq analysis.","authors":"Jing Ma, Zhinan Chen, Limin Hou","doi":"10.18632/aging.206043","DOIUrl":"https://doi.org/10.18632/aging.206043","url":null,"abstract":"<p><strong>Purpose: </strong>Proliferation of stromal connective tissue is a hallmark of pancreatic adenocarcinoma (PAAD). The engagement of activated cancer-associated fibroblasts (CAFs) contributes to the progression of PAAD through their involvement in tumor fibrogenesis. However, the prognostic significance of CAF-based risk signature in PAAD has not been explored.</p><p><strong>Methods: </strong>The single-cell RNA sequencing (scRNA-seq) data sourced from GSE155698 within the Gene Expression Omnibus (GEO) database was supplemented by bulk RNA sequencing data from The Cancer Genome Atlas (TCGA) and microarray data retrieved from the GEO database. The scRNA-seq data underwent processing via the Seurat package to identify distinct CAF clusters utilizing specific CAF markers. Differential gene expression analysis between normal and tumor samples was conducted within the TCGA-PAAD cohort. Univariate Cox regression analysis pinpointed genes associated with CAF clusters, identifying prognostic CAF-related genes. These genes were utilized in LASSO regression to craft a predictive risk signature. Subsequently, integrating clinicopathological traits and the risk signature, a nomogram model was constructed.</p><p><strong>Results: </strong>Our scRNA-seq analysis unveiled four distinct CAF clusters in PAAD, with two linked to PAAD prognosis. Among 207 identified DEGs, 148 exhibited significant correlation with these CAF clusters, forming the basis of a seven-gene risk signature. This signature emerged as an independent predictor in multivariate analysis for PAAD and demonstrated predictive efficacy in immunotherapeutic outcomes. Additionally, a novel nomogram, integrating age and the CAF-based risk signature, exhibited robust predictability and reliability in prognosticating PAAD. Moreover, the risk signature displayed substantial correlations with stromal and immune scores, as well as specific immune cell types.</p><p><strong>Conclusions: </strong>The prognosis of PAAD can be accurately predicted using the CAF-based risk signature, and a thorough analysis of the PAAD CAF signature may aid in deciphering the patient's immunotherapy response and presenting fresh cancer treatment options.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"DDIT3 switches osteogenic potential of BMP9 to lipogenic by attenuating Wnt/β-catenin signaling via up-regulating DKK1 in mesenchymal stem cells.","authors":"Hong-Hong Luo, Wen-Yan Ren, Ai-Hua Ye, Lu Liu, Yue Jiang, Fang-Lin Ye, Bai-Cheng He, Zhen-Hua Chen","doi":"10.18632/aging.206091","DOIUrl":"https://doi.org/10.18632/aging.206091","url":null,"abstract":"<p><p>Bone morphogenetic protein 9 (BMP9) functions as a potent inducer of osteogenic differentiation in mesenchymal stem cells (MSCs), holding promise for bone tissue engineering. However, BMP9 also concurrently triggers lipogenic differentiation in MSCs, potentially compromising its osteogenic potential. In this study, we explored the role of DNA damage inducible transcript 3 (DDIT3) in regulating the balance between BMP9-induced osteogenic and lipogenic differentiation in MSCs. Utilizing techniques such as PCR, Western blot, histochemical staining, and <i>in vivo</i> experiments, we analyzed the osteogenic and lipogenic markers induced by BMP9 and delved into the underlying molecular mechanism. We found a significant upregulation of DDIT3 in C3H10T1/2 cells treated with BMP9. This upregulation led to a reduction in BMP9-induced osteogenic markers but an enhancement in lipogenic markers. Conversely, knocking down DDIT3 produced the opposite effects. Furthermore, BMP9-induced bone formation was decreased in the presence of DDIT3, but adipocyte formation was increased. Further investigations demonstrated that BMP9 increased the phosphorylation level of GSK-3β and promoted nuclear translocation of β-catenin, both of which were suppressed by DDIT3. Moreover, DDIT3 decreased the total β-catenin protein level while BMP9 increased the DKK1 protein level, which was further enhanced by DDIT3. Notably, knocking down DKK1 partially reversed the effect of DDIT3 on reducing BMP9-induced osteogenic markers and increasing lipogenic markers. Our findings indicated that DDIT3 enhances lipogenic differentiation by diminishing BMP9's osteogenic potential, possibly through inhibiting Wnt/β-catenin signaling via DKK1 upregulation in MSCs.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frailty and pre-frailty associated with long-term diminished physical performance and quality of life in breast cancer and hematopoietic cell transplant survivors.","authors":"Najla El Jurdi, Hok Sreng Te, Qing Cao, Char Napurski, Shuo Wang, Andre Robinson, Mukta Arora, Heba ElHusseini, Fiona He, Laura J Niedernhofer, Bharat Thyagarajan, Anna Prizment, Shernan Holtan, Anne Hudson Blaes, Matthew J Yousefzadeh","doi":"10.18632/aging.206109","DOIUrl":"https://doi.org/10.18632/aging.206109","url":null,"abstract":"<p><p>Physical frailty as a sign of accelerated aging is not well characterized in breast cancer (BC) and hematopoietic cell transplant (HCT) survivors and its correlation with outcomes and quality of life (QOL) is not defined. We conducted a prospective study to determine the prevalence of frailty in adult BC and HCT survivors, examine its impact on QOL, and determine its association with <i>p16^INK4a</i>, a molecular biomarker for biological aging. The study included 59 BC and 65 HCT survivors. Median age was 60 years (range 27-81), 68.5% were female and 49.2% were 18-59 vs. 51.8% ≥60 years old. A total of 71 (57.3%) were \"fit\" (frailty score 0) vs. 53 (42.7%) were pre-frailty/frail (frailty scores ≥1), and of the latter 17 (32.1%) were BC and 36 (67.9%) HCT patients. On multivariate analysis, patients >60 years were twice as likely to be frail (OR 2.04, 95% CI, 0.96-4.33; p=0.07), HCT were more likely to be frail compared to BC patients, and female HCT had 2.43 (95% CI, 0.92-6.40) and male HCT patients had 3.25 (95% CI, 1.37-7.72) times higher risk of frail; p=0.02. Frailty was associated with significant decline in QOL, measured by Medical Outcomes Study (MOS) Short Form 36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS), and FACT (Functional Assessment of Cancer Therapy) scores. <i>p16^INK4a</i> expression was higher in those who were frail, older than 60, and with higher expression in frail vs. fit patients who are 18-59 years. Our study highlights the high prevalence of frailty in survivors with detrimental effects on physical and overall wellbeing, and supports an association between frailty and the senescence marker <i>p16^INK4a</i>.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142333052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling senescence-associated secretory phenotype in epidermal aging: insights from reversibly immortalized keratinocytes.","authors":"Lu-Wen Xu, Yi-Dan Sun, Qiao-Yu Fu, Dan Wu, Jian Lin, Chen Wang, Liang Zhang, Cai-Yue Liu, Qing-Feng Li","doi":"10.18632/aging.206117","DOIUrl":"https://doi.org/10.18632/aging.206117","url":null,"abstract":"<p><p>Aging of epidermal keratinocytes profoundly impacts skin health, contributing to changes in appearance, barrier function, and susceptibility to diseases. Despite its significance, the molecular mechanisms underlying epidermal aging remain elusive. In this study, a reversible immortalized cell line was established by expressing SV40T in keratinocytes using the Tet-Off lentiviral system. Inducing a senescent phenotype by terminating SV40T expression revealed a significant reduction in mitotic ability, as well as characteristics of cellular aging. RNA sequencing analysis revealed alterations in gene expression and signaling pathways including DNA repair dysfunction, notably senescence-associated secretory phenotype (SASP)-related genes, such as MMP1, SERPINB2 and VEGFA. Our study provides insights into the molecular mechanisms of epidermal aging, offering potential therapeutic targets and highlighting the role of SASP in the aging process.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142309192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the therapeutic mechanism of Yuebi decoction on nephrotic syndrome based on network pharmacology and experimental study.","authors":"Tianwen Yao, Qingliang Wang, Shisheng Han, Yanqiu Xu, Min Chen, Yi Wang","doi":"10.18632/aging.206116","DOIUrl":"https://doi.org/10.18632/aging.206116","url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to explore the material basis of YBD and its possible mechanisms against NS through network pharmacology, molecular docking, and <i>in vivo</i> experiment.</p><p><strong>Methods: </strong>Active ingredients and potential targets of YBD were obtained through TCMSP and SwissTargetPrediction. NS-related targets were obtained from GeneCards, PharmGKB, and OMIM databases. The herb-ingredient-target network and PPI network were constructed by Cytoscape 3.9.1 and STRING database. GO and KEGG analyses were performed by DAVID database and ClueGO plugin. The connection between main active ingredients and core targets were revealed by molecular docking. To ascertain the effects and molecular mechanisms of YBD, a rat model was established by PAN.</p><p><strong>Results: </strong>We collected 124 active ingredients, 269 drug targets, and 2089 disease targets. 119 overlapping were screened for subsequent analysis. PPI showed that AKT1, STAT3, TRPC6, CASP3, JUN, PPP3CA, IL6, PTGS2, VEGFA, and NFATC3 were potential therapeutic targets of YBD against NS. Through GO and KEGG analyses, it showed the therapeutic effect of YBD on NS was closely involved in the regulation of pathways related to podocyte injury, including AGE-RAGE signaling pathway in diabetic complications and MAPK signaling pathway. Five key bioactive ingredients of YBD had the good affinity with the core targets. the experiment confirmed the renoprotective effects of YBD through reducing podocyte injury. Furthermore, YBD could downregulate expressions of PPP3CA, STAT3, NFATC3, TRPC6, and AKT1 in rats.</p><p><strong>Conclusions: </strong>YBD might be a potential drug in the treatment of NS, and the underlying mechanism is closely associated with the inhibition of podocyte injury.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301697","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Characterization of a ferroptosis-related gene signature predicting survival and immunotherapeutic response in lung adenocarcinoma.","authors":"Chuan Zhang, Yingying Su, Hongrui Wang, Dan Dang, Xin Huang, Shuyou Shi, Yue Shi, Peng Zhang, Ming Yang","doi":"10.18632/aging.206110","DOIUrl":"https://doi.org/10.18632/aging.206110","url":null,"abstract":"<p><p>Lung cancer remains the leading cause of cancer-related death worldwide, and drug resistance represents the main obstacle responsible for the poor mortality and prognosis. Here, to identify a novel gene signature for predicting survival and drug response, we jointly investigated RNA sequencing data of lung adenocarcinoma patients from TCGA and GEO databases, and identified a ferroptosis-related gene signature. The signature was validated in the validation set and two external cohorts. The high-risk group had a reduced survival than the low-risk group (<i>P</i> < 0.05). Moreover, the established gene signature was associated with tumor mutation burden, microsatellite instability, and response to immune checkpoint blockade. In addition, four candidate oncogenes (<i>RRM2</i>, <i>SLC2A1</i>, <i>DDIT4</i>, and <i>VDAC2</i>) were identified to be candidate oncogenes using <i>in silico</i> and wet experiments, which could serve as potential therapeutic targets. Collectively, this study developed a novel ferroptosis-related gene signature for predicting prognosis and drug response, and identified four candidate oncogenes for lung adenocarcinoma.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Determinants of cerebral blood flow and arterial transit time in healthy older adults.","authors":"Jack Feron, Katrien Segaert, Foyzul Rahman, Sindre H Fosstveit, Kelsey E Joyce, Ahmed Gilani, Hilde Lohne-Seiler, Sveinung Berntsen, Karen J Mullinger, Samuel J E Lucas","doi":"10.18632/aging.206112","DOIUrl":"https://doi.org/10.18632/aging.206112","url":null,"abstract":"<p><p>Cerebral blood flow (CBF) and arterial transit time (ATT), markers of brain vascular health, worsen with age. The primary aim of this cross-sectional study was to identify modifiable determinants of CBF and ATT in healthy older adults (<i>n</i> = 78, aged 60-81 years). Associations between cardiorespiratory fitness and CBF or ATT were of particular interest because the impact of cardiorespiratory fitness is not clear within existing literature. Secondly, this study assessed whether CBF or ATT relate to cognitive function in older adults. Multiple post-labelling delay pseudo-continuous arterial spin labelling estimated resting CBF and ATT in grey matter. Results from multiple linear regressions found higher BMI was associated with lower global CBF (β = -0.35, <i>P</i> = 0.008) and a longer global ATT (β = 0.30, <i>P</i> = 0.017), global ATT lengthened with increasing age (β = 0.43, <i>P</i> = 0.004), and higher cardiorespiratory fitness was associated with longer ATT in parietal (β = 0.44, <i>P</i> = 0.004) and occipital (β = 0.45, <i>P</i> = 0.003) regions. Global or regional CBF or ATT were not associated with processing speed, working memory, or attention. In conclusion, preventing excessive weight gain may help attenuate age-related declines in brain vascular health. ATT may be more sensitive to age-related decline than CBF, and therefore useful for early detection and management of cerebrovascular impairment. Finally, cardiorespiratory fitness appears to have little effect on CBF but may induce longer ATT in specific regions.</p>","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142301796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}