IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-20 DOI: 10.18632/aging.206331

Vivien Hoof, Nicolas Casadei, Olaf Riess, Julia Schulze-Hentrich, Thomas Hentrich

{"title":"Brain region-specific and systemic transcriptomic alterations in a human alpha-synuclein overexpressing rat model.","authors":"Vivien Hoof, Nicolas Casadei, Olaf Riess, Julia Schulze-Hentrich, Thomas Hentrich","doi":"10.18632/aging.206331","DOIUrl":"https://doi.org/10.18632/aging.206331","url":null,"abstract":"Synucleinopathies are age-dependent neurodegenerative diseases characterized by alpha-synuclein accumulation with distinct vulnerabilities across brain regions. Understanding early disease stages is essential to uncover initial molecular changes that might enable earlier diagnosis and causal therapy. In this study, we profiled longitudinal and brain region-resolved gene expression changes in a rat model of synucleinopathies overexpressing human SNCA. Transcriptomic analyses were performed on gene and transcript level of striatal, frontocortical, and cerebellar tissue in 5- and 12-month-old transgenic (BAC SNCA) and wild type rats revealing that SNCA overexpression leads to age-dependent transcriptomic changes that largely occur region-specific. In frontal cortex, dysregulation of myelination-associated genes agreed with Parkinson patient data as shown before. In addition, BAC SNCA rats displayed more gene expression changes at younger age, with a common and characteristic alteration pattern across all three examined brain regions. We also identified a cross-regional set of differential genes that were affected by SNCA overload. This set was also partially reflected in the gut transcriptome of the same rat model, suggesting a systemic impact of SNCA overload. Taken together, our findings highlight both brain region-specific vulnerabilities and global molecular perturbations associated with alpha-synuclein biology and provide insights into early transcriptomic changes in synucleinopathies.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145338274","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}

引用次数: 0

Hospitalization with infections and risk of Dementia: a systematic review and meta-analysis. 感染住院与痴呆风险：系统回顾和荟萃分析

IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-13 DOI: 10.18632/aging.206329

Wei Yu Chua, Jia Dong James Wang, Claire Kar Min Chan, Ling-Ling Chan, Eng-King Tan

{"title":"Hospitalization with infections and risk of Dementia: a systematic review and meta-analysis.","authors":"Wei Yu Chua, Jia Dong James Wang, Claire Kar Min Chan, Ling-Ling Chan, Eng-King Tan","doi":"10.18632/aging.206329","DOIUrl":"https://doi.org/10.18632/aging.206329","url":null,"abstract":"Background: Dementia affects more than 50 million people worldwide, with 10 million new diagnosis each year. The link between hospitalization with infections and risk of Dementia is unclear. We conducted a meta-analysis on the association between hospitalization with infection and risk of Dementia.Methods: We searched MEDLINE and Embase from inception to March 31, 2025 to identify cohort studies comparing the frequency of Dementia in patients hospitalized with infections with those without. We computed hazard ratios (HR) for each study and pooled the results using a random-effects meta-analysis.Results: Out of 1900 studies that were screened initially, 16 studies comprising 4,266,276 patients were included for analysis. Hospitalization with infection was associated with an increased risk of all-cause Dementia (HR: 1.83, 95% CI: 1.58-2.13, p < 0.0001), Alzheimer's Disease (AD) (HR: 1.60, 95% CI: 1.23-2.08, p < 0.001) and Vascular Dementia (HR: 3.68, 95% CI: 2.16-6.27, p < 0.001). Among the infections, having Sepsis (HR: 1.78, 95% CI: 1.53-2.08) was associated with the highest risk of all-cause Dementia, followed by Pneumonia, Urinary Tract Infections, Skin and Soft Tissue infections.Conclusions: Our meta-analysis showed that hospitalization with infection was associated with increased risk of Dementia. Sepsis carried the highest risk, followed by Pneumonia, Urinary Tract Infections, Skin and Soft Tissue infections.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145287879","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}

引用次数: 0

Longevity clinics: between promise and peril. 长寿诊所：在希望与危险之间。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-13 DOI: 10.18632/aging.206330

Marco Demaria

引用次数: 0

Identification of key genes with differential correlations in prostate cancer. 前列腺癌差异相关关键基因的鉴定。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-10 DOI: 10.18632/aging.206323

Zepai Chi, Yuanfeng Zhang, Xuwei Hong, Tenghao Yang, Qingchun Xu, Weiqiang Lin, Yueying Huang, Yonghai Zhang

{"title":"Identification of key genes with differential correlations in prostate cancer.","authors":"Zepai Chi, Yuanfeng Zhang, Xuwei Hong, Tenghao Yang, Qingchun Xu, Weiqiang Lin, Yueying Huang, Yonghai Zhang","doi":"10.18632/aging.206323","DOIUrl":"https://doi.org/10.18632/aging.206323","url":null,"abstract":"Background: Prostate cancer, a major global health issue for men, remains a critical clinical challenge in treatment, highlighting the need for improved biomarkers. Treatment options for prostate cancer include active surveillance, surgery, endocrine therapy, chemotherapy, radiotherapy, immunotherapy, etc. However, as the tumor progresses, the effectiveness of treatment regimens gradually decreases. Therefore, we need to understand the biological mechanisms that promote prostate cancer tumorigenesis and progression and to screen biomarkers for diagnosis and prediction of prognosis.Methods: We utilized the expression profiles of prostate cancer from The Cancer Genome Atlas (TCGA) database and employed weighted gene co-expression network analysis (WGCNA) to construct a gene interaction network. Gene co-expression networks were constructed using WGCNA (soft-threshold power β = 10, scale-free R² > 0.9), with differential correlations computed via Fisher's z-test (FDR < 0.05). We used the \"DiffCorr\" package to discriminate between tumor and adjacent normal tissues to identify genes with differential representation in tumor and normal tissues, and perform in-depth analysis of these genes.Results: Through WGCNA analysis, we identified a total of 20 modules, three gene modules were significantly associated with prostate cancer. We then analyzed the genes in these modules separately by the \"DiffCorr\" package and intersected these with differentially expressed genes. Finally, 21 genes were screened as biomarkers for prostate cancer.Conclusions: Our study unveils a prostate cancer tumorigenesis mechanism by identifying differentially correlated gene pairs during normal-to-tumor transformation. We believe that the biomarkers derived from this algorithm have important reference implications for future research in prostate cancer.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281916","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}

引用次数: 0

Developmental arrest rate of an embryo cohort correlates with advancing reproductive age, but not with the aneuploidy rate of the resulting blastocysts in good prognosis patients: a study of 25,974 embryos. 胚胎群的发育停止率与生育年龄的提高有关，但与预后良好患者的囊胚非整倍体率无关：一项对25,974个胚胎的研究。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-10 DOI: 10.18632/aging.206328

Andres Reig, Emre Seli

{"title":"Developmental arrest rate of an embryo cohort correlates with advancing reproductive age, but not with the aneuploidy rate of the resulting blastocysts in good prognosis patients: a study of 25,974 embryos.","authors":"Andres Reig, Emre Seli","doi":"10.18632/aging.206328","DOIUrl":"https://doi.org/10.18632/aging.206328","url":null,"abstract":"This study aimed to investigate the extent to which developmental arrest rate in embryos generated using assisted reproduction correlate with female age and the rate of aneuploidy in the cohort. A total of 25,974 embryos from 1,928 cohorts were included in the study, with an overall embryo developmental arrest (EDA) rate of 40.3% (95% CI: 39.8-40.9%). The median EDA rate increased with age: 33.0% (IQR: 22.0-50-0%) in <35 years old, 38.0% (25.0-50.0%) in 35-37 years old, 40.0% (29.0-54.0%) in 38-40 years old, 44.0% (38.8-56.5%) in 41-42 years old, and 44.0% (40.0-58.0%) in >42 years old; p < 0.0001. A very weak positive correlation was identified between EDA rate and the rate of aneuploidy (r: 0.07, 95% CI 0.03-0.11; R2: 0.00, p < 0.01) when evaluating all cohorts. However, when adjusting for age, no statistically significant relationship between aneuploidy and EDA was observed. Our findings suggest that the rate of EDA and the rate of whole chromosome aneuploidy in the resulting blastocyst cohort are both associated with female age, but not with each other. Therefore, EDA and aneuploidy rates represent two independent factors in determining the number of euploid embryos available for transfer and the overall likelihood of ART success.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145281842","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}

引用次数: 0

Growth hormone excess drives liver aging via increased glycation stress. 生长激素过量通过增加糖基化应激驱动肝脏衰老。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-03 DOI: 10.18632/aging.206327

Parminder Singh, Anil Gautam, Marissa N Trujillo, Praveen Singh, Lizbeth Enriquez Najera, James J Galligan, Lisa Hensley, Pankaj Kapahi, Andrzej Bartke

{"title":"Growth hormone excess drives liver aging via increased glycation stress.","authors":"Parminder Singh, Anil Gautam, Marissa N Trujillo, Praveen Singh, Lizbeth Enriquez Najera, James J Galligan, Lisa Hensley, Pankaj Kapahi, Andrzej Bartke","doi":"10.18632/aging.206327","DOIUrl":"10.18632/aging.206327","url":null,"abstract":"Growth hormone (GH) plays a crucial role in various physiological functions, with its secretion tightly regulated by complex endocrine mechanisms. Pathological conditions such as acromegaly or pituitary tumors result in elevated circulating GH levels, which have been implicated in a spectrum of metabolic disorders, potentially by regulating liver metabolism. In this study, we focused on the liver, a key organ in metabolic regulation and a primary target of GH, to investigate the impact of high circulating GH on liver metabolism. We used bovine GH overexpressing transgenic (bGH-Tg) mice to conduct a comprehensive transcriptomic analysis of hepatic tissues. The bGH-Tg mouse livers exhibit dysregulated fatty acid metabolism and heightened inflammatory responses. Notably, the transcriptomic profile of young bGH-Tg mouse livers resembled that of aged livers and displayed markers of increased cellular senescence. Furthermore, these mice exhibited a significant accumulation of advanced glycation end products (AGEs). Intervention with glycation-lowering compounds effectively reversed the insulin resistance and aberrant transcriptomic signatures in the liver that are associated with elevated GH levels. These findings underscore the potential therapeutic value of glycation-lowering agents in mitigating the deleterious effects of chronic GH overexpression.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228640","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}

引用次数: 0

The role of phenylalanine and tyrosine in longevity: a cohort and Mendelian randomization study. 苯丙氨酸和酪氨酸在长寿中的作用：一项队列和孟德尔随机研究。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-03 DOI: 10.18632/aging.206326

Jie V Zhao, Yitang Sun, Junmeng Zhang, Kaixiong Ye

{"title":"The role of phenylalanine and tyrosine in longevity: a cohort and Mendelian randomization study.","authors":"Jie V Zhao, Yitang Sun, Junmeng Zhang, Kaixiong Ye","doi":"10.18632/aging.206326","DOIUrl":"https://doi.org/10.18632/aging.206326","url":null,"abstract":"Background: Protein restriction increases lifespan, however, the specific amino acids affecting lifespan are unclear. Tyrosine and its precursor, phenylalanine, may influence lifespan through their response to low-protein diet, with possible sex disparity.Methods: We applied cohort study design and Mendelian randomization (MR) analysis. Specifically, we examined the overall and sex-specific relationships between circulating phenylalanine and tyrosine and all-cause mortality in the UK Biobank using Cox regression. To test causality, in two-sample MR analysis, we used genetic variants associated with phenylalanine and tyrosine in UK Biobank with genome-wide significance and uncorrelated (r2 < 0.001) with each other, and applied them to large genome-wide association studies of lifespan, including parental, paternal, and maternal attained ages in the UK Biobank. We also conducted multivariable MR to examine the independent role of phenylalanine and tyrosine.Results: Tyrosine was associated with shorter lifespan in both observational and MR study, with potential sex disparity. After controlling for phenylalanine using multivariable MR, tyrosine remained related to a shorter lifespan in men (-0.91 years of life, 95% confidence interval (CI) -1.60 to -0.21) but not in women (-0.36 years, 95% CI -0.96 to 0.23). Phenylalanine showed no association with lifespan in either men or women after controlling for tyrosine.Conclusions: Reducing tyrosine in people with elevated concentrations may contribute to prolonging lifespan, with potential sex-specific differences. It is worthwhile to explore pathways underlying the sex-specific effects.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228726","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}

引用次数: 0

L-β-aminoisobutyric acid (L-BAIBA) in combination with voluntary wheel running exercise enhances musculoskeletal properties in middle-age male mice. L-β-氨基异丁酸（L- baiba）联合自主轮跑运动可增强中年雄性小鼠的肌肉骨骼特性。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-10-01 DOI: 10.18632/aging.206325

Julian A Vallejo, Yukiko Kitase, Thiagarajan Ganesh, Mark Dallas, Yixia Xie, David S Moore, Mark L Johnson, Lynda F Bonewald, Michael J Wacker

{"title":"L-β-aminoisobutyric acid (L-BAIBA) in combination with voluntary wheel running exercise enhances musculoskeletal properties in middle-age male mice.","authors":"Julian A Vallejo, Yukiko Kitase, Thiagarajan Ganesh, Mark Dallas, Yixia Xie, David S Moore, Mark L Johnson, Lynda F Bonewald, Michael J Wacker","doi":"10.18632/aging.206325","DOIUrl":"https://doi.org/10.18632/aging.206325","url":null,"abstract":"Contracting skeletal muscles secrete the metabolite L-β-aminoisobutyric acid (L-BAIBA), which when supplemented in the diet can mitigate disuse-induced musculoskeletal dysfunction. However, the effects of L-BAIBA supplementation alone and combined with exercise on cardiac and musculoskeletal properties are currently unknown. We hypothesized that exercise with L-BAIBA supplementation would promote greater cardiac and musculoskeletal benefits than exercise alone. To investigate this hypothesis, we subjected 12-month-old (as a model of middle-age) male C57BL6 mice to voluntary wheel running (VWR) with L-BAIBA (100mg/kg/day) (VWR+L-BAIBA), VWR alone, L-BAIBA alone, or none (CTRL) for three months. After the intervention, conscious electrocardiogram showed slightly prolonged QTc in VWR+L-BAIBA mice compared to CTRL (p<0.05). Soleus muscles from VWR+L-BAIBA, but not VWR, were larger, contracted more forcefully, and contained more slow-oxidative type I myofibers compared to CTRL (p<0.05). In EDL muscle, VWR but not VWR+L-BAIBA improved fatigue resistance and caffeine-induced recovery (p<0.05). In bone, VWR+L-BAIBA but not VWR showed lower bone marrow adiposity, higher trabecular thickness, and connectivity, smaller bone diameter and Moment of Inertia, but higher Modulus of Elasticity than CTRL (p<0.05), suggesting L-BAIBA delays aging-induced periosteal expansion due to better bone material qualities. These findings suggest a physiological interaction between exercise and L-BAIBA supplementation to improve soleus muscle and bone properties and reduce bone marrow adiposity.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145228699","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}

引用次数: 0

Correction for: The regulation of p53 by phosphorylation: a model for how distinct signals Integrate into the p53 pathway. 修正：磷酸化对p53的调节：一个不同信号如何整合到p53通路的模型。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-09-30 DOI: 10.18632/aging.206321

Nicola J Maclaine, Ted R Hupp

引用次数: 0

Retraction of: Long non-coding RNA NNT-AS1 promotes cholangiocarcinoma cells proliferation and epithelial-to-mesenchymal transition through down-regulating miR-203. 长链非编码RNA NNT-AS1的回缩通过下调miR-203促进胆管癌细胞增殖和上皮-间质转化。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-09-30 DOI: 10.18632/aging.206322

Yulei Gu, Zhiqiang Zhu, Hui Pei, Dong Xu, Yumin Jiang, Luanluan Zhang, Lili Xiao

引用次数: 0

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