Aging-Us最新文献_第8页

Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey. 全国健康与营养调查中环境化学物质暴露与表观遗传老化的关联研究。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-02-11 DOI: 10.18632/aging.206201

Dennis Khodasevich, Nicole Gladish, Saher Daredia, Anne K Bozack, Hanyang Shen, Jamaji C Nwanaji-Enwerem, Belinda L Needham, David H Rehkopf, Andres Cardenas

{"title":"Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey.","authors":"Dennis Khodasevich, Nicole Gladish, Saher Daredia, Anne K Bozack, Hanyang Shen, Jamaji C Nwanaji-Enwerem, Belinda L Needham, David H Rehkopf, Andres Cardenas","doi":"10.18632/aging.206201","DOIUrl":"10.18632/aging.206201","url":null,"abstract":"Epigenetic clocks can serve as pivotal biomarkers linking environmental exposures with biological aging. However, research on the influence of environmental exposures on epigenetic aging has largely been limited to a small number of chemicals and specific populations. We harnessed data from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles to examine exposome-wide associations between environmental exposures and epigenetic aging. A total of 8 epigenetic aging biomarkers were obtained from whole blood in 2,346 participants ranging from 50-84 years of age. A total of 64 environmental exposures including phthalates, metals, pesticides, dioxins, and polychlorinated biphenyls (PCBs) were measured in blood and urine. Associations between log2-transformed/standardized exposure measures and epigenetic age acceleration (EAA) were assessed using survey-weighted generalized linear regression. A 1 standard deviation (SD) increase in log2 serum cadmium levels was associated with higher GrimAge acceleration (beta = 1.23 years, p = 3.63e-06), higher GrimAge2 acceleration (beta = 1.27 years, p = 1.62e-05), and higher DunedinPoAm (beta = 0.02, p = 2.34e-05). A 1 SD increase in log2 serum cotinine levels was associated with higher GrimAge2 acceleration (beta = 1.40 years, p = 6.53e-04) and higher DunedinPoAm (beta = 0.03, p = 6.31e-04). Associations between cadmium and EAA across several clocks persisted in sensitivity models adjusted for serum cotinine levels, and other associations involving lead, dioxins, and PCBs were identified. Several environmental exposures are associated with epigenetic aging in a nationally representative US adult population, with particularly strong associations related to cadmium and cotinine across several epigenetic clocks.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"408-430"},"PeriodicalIF":3.9,"publicationDate":"2025-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892924/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143411706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the role of acylated ghrelin and gut microbiome in delineating cognitive health in the elderly. 探讨酰化胃饥饿素和肠道微生物组在描述老年人认知健康中的作用。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-02-07 DOI: 10.18632/aging.206200

Sudeshna Rout, Rishikesh Dash, Varsha Satish, Giriprasad Venugopal, Bodepudi Narasimha Rao, Debapriya Bandhyopadhyay, Sanjeev Kumar Bhoi, Balamurugan Ramadass

{"title":"Exploring the role of acylated ghrelin and gut microbiome in delineating cognitive health in the elderly.","authors":"Sudeshna Rout, Rishikesh Dash, Varsha Satish, Giriprasad Venugopal, Bodepudi Narasimha Rao, Debapriya Bandhyopadhyay, Sanjeev Kumar Bhoi, Balamurugan Ramadass","doi":"10.18632/aging.206200","DOIUrl":"10.18632/aging.206200","url":null,"abstract":"Introduction: With increased life expectancy, there is an increase in aging population and prevalence of dementia. Ghrelin is a key regulator of spatial memory and cognition. The gut microbiome may affect the circulating levels of unacylated ghrelin (UAG) and acylated ghrelin (AG). Thus, we explore the potential association of the gut microbiome, AG, and cognitive health in the aging dementia patient.Methods: 40 dementia patients and 40 controls were recruited. Fecal Microbiome analysis using 16S rRNA sequencing was performed on 18 samples. A mixed-method approach was employed for robust interpretation.Results: Dementia patients had an increased serum AG and AG/UAG ratio. With the increase in AG among dementia subjects, a significant decrease in species richness was observed. Bifidobacterium longum, Eubacterium biforme, Fecalibacterium prausnitzii, Lactobacillus ruminis, and Prevotella copri contributed to substantial differences in beta-diversity. Blautia obeum was associated with Mini-Mental State Examination (MMSE), and Fecalibacterium prausnitzii was associated with Montreal Cognitive Assessment (MoCA) Scale.Discussion: This pilot study indicates a complex interaction between AG, gut microbiome, and cognitive scores. Increased AG corresponds to both dementia and gut dysbiosis, intricately interconnecting the gut-brain axis. The circulating AG and associated gut microbiome might be a putative biomarker for dementia.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"393-407"},"PeriodicalIF":3.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143384173","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Mitochondrial dysfunction, iron accumulation, lipid peroxidation, and inflammasome activation in cellular models derived from patients with multiple sclerosis. 来自多发性硬化症患者的细胞模型中的线粒体功能障碍、铁积累、脂质过氧化和炎性体激活

IF 3.9 3区医学

Aging-Us Pub Date : 2025-02-06 DOI: 10.18632/aging.206198

Raquel García-Salas, Paula Cilleros-Holgado, Anna Di Spirito, David Gómez-Fernández, Rocío Piñero-Pérez, José Manuel Romero-Domínguez, Mónica Álvarez-Córdoba, Diana Reche-López, Ana Romero-González, Alejandra López-Cabrera, José Antonio Sánchez-Alcázar

{"title":"Mitochondrial dysfunction, iron accumulation, lipid peroxidation, and inflammasome activation in cellular models derived from patients with multiple sclerosis.","authors":"Raquel García-Salas, Paula Cilleros-Holgado, Anna Di Spirito, David Gómez-Fernández, Rocío Piñero-Pérez, José Manuel Romero-Domínguez, Mónica Álvarez-Córdoba, Diana Reche-López, Ana Romero-González, Alejandra López-Cabrera, José Antonio Sánchez-Alcázar","doi":"10.18632/aging.206198","DOIUrl":"10.18632/aging.206198","url":null,"abstract":"Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Despite advancements in managing relapsing active illness, effective treatments for the irreversible progressive decline in MS remain limited. Research employing skin fibroblasts obtained from patients with neurological disorders revealed modifications in cellular stress pathways and bioenergetics. However, research using MS patient-derived cellular models is scarce. In this study, we collected fibroblasts from two MS patients to investigate cellular pathological alterations. We observed that MS fibroblasts showed a senescent morphology associated with iron/lipofuscin accumulation and altered expression of iron metabolism proteins. In addition, we found increased lipid peroxidation and downregulation of antioxidant enzymes expression levels in MS fibroblasts. When challenged against erastin, a ferroptosis inducer, MS fibroblasts showed decreased viability, suggesting increased sensitivity to ferroptosis. Furthermore, MS fibroblasts presented alterations in the expression levels of autophagy-related proteins. Interestingly, these alterations were associated with mitochondrial dysfunction and inflammasome activation. These findings were validated in 7 additional patient-derived cell lines. Our findings suggest that the underlying stress phenotype of MS fibroblasts may be disease-specific and recapitulate the main cellular pathological alterations found in the disease such as mitochondrial dysfunction, iron accumulation, lipid peroxidation, inflammasome activation, and pro-inflammatory cytokine production.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"365-392"},"PeriodicalIF":3.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892916/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143371374","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Carriers of Parkinson's disease-linked SNCA Rep1 variant have greater non-motor decline: a 4 year follow up study. 帕金森病相关SNCA Rep1变异的携带者有更大的非运动能力下降：一项为期4年的随访研究

IF 3.9 3区医学

Aging-Us Pub Date : 2025-02-03 DOI: 10.18632/aging.206196

Aarthi Santhanakrishnan, Yi Jayne Tan, Seyed Ehsan Saffari, Yi Zhao, Ebonne Y L Ng, Samuel Y E Ng, Nicole S Y Chia, Xinyi Choi, Dede Heng, Shermyn Neo, Zheyu Xu, Kay Yaw Tay, Wing Lok Au, Eng-King Tan, Louis C S Tan, Adeline S L Ng

引用次数: 0

Cysteinyl leukotriene receptor 1 modulates retinal immune cells, vascularity and proteolytic activity in aged mice. 半胱氨酸白三烯受体1调节老年小鼠视网膜免疫细胞、血管和蛋白水解活性。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-01-31 DOI: 10.18632/aging.206193

Andreas Koller, Julia Preishuber-Pflügl, Daniela Mayr, Susanne Maria Brunner, Anja-Maria Ladek, Christian Runge, Ludwig Aigner, Herbert Anton Reitsamer, Andrea Trost

{"title":"Cysteinyl leukotriene receptor 1 modulates retinal immune cells, vascularity and proteolytic activity in aged mice.","authors":"Andreas Koller, Julia Preishuber-Pflügl, Daniela Mayr, Susanne Maria Brunner, Anja-Maria Ladek, Christian Runge, Ludwig Aigner, Herbert Anton Reitsamer, Andrea Trost","doi":"10.18632/aging.206193","DOIUrl":"10.18632/aging.206193","url":null,"abstract":"Cysteinyl leukotrienes (CysLTs) modulate the immune response, the microvasculature, cell stress and the endosomal-lysosomal system, and are involved in cellular aging. Interestingly, CysLT receptor 1 (Cysltr1) is highly expressed in the retina, a tissue that is strongly affected by the aging process. Thus, we performed an introductory examination to determine a potential importance of Cysltr1 for cells in the neurovascular unit using qPCR and immunofluorescence analysis, and on proteolytic activity in the retinas of aged mice. Aged mice (~84 weeks) were treated orally with vehicle or 10 mg/kg montelukast (MTK), a specific Cysltr1 inhibitor, for 8 weeks, 5x/week. The retinas of young mice (~11 weeks) served as controls. Compared with young control mice, aged mice exhibited increased numbers of microglia and a reduced retinal capillary diameter, but these age-dependent changes were abrogated by MTK treatment. Retinal protein levels of the ubiquitin binding protein sequestosome-1 were amplified by aging, but were reduced by MTK treatment. Interestingly, retinal proteasome activity was decreased in aged mice, whereas Cysltr1 inhibition increased this activity. The reduction in immune cells caused by Cysltr1 suppression may dampen neuroinflammation, a known promoter of tissue aging. Additionally, an increase in capillary diameter after Cysltr1 inhibition could have a beneficial effect on blood flow in aged individuals. Furthermore, the increase in proteolytic activity upon Cysltr1 inhibition could prevent the accumulation of toxic deposits, which is a hallmark of aged tissue. Overall, Cysltr1 is a promising target for modulating the impact of aging on retinal tissue.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"308-328"},"PeriodicalIF":3.9,"publicationDate":"2025-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892928/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143076583","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction for: The association between KLF4 as a tumor suppressor and the prognosis of hepatocellular carcinoma after curative resection. 更正：KLF4作为肿瘤抑制因子与肝细胞癌根治性切除后预后的关系。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-01-31 DOI: 10.18632/aging.206197

Min Xue, Chenhao Zhou, Yan Zheng, Ziping Zhang, Shun Wang, Yan Fu, Manar Atyah, Xiaolong Xue, Le Zhu, Qiongzhu Dong, Huliang Jia, Ning Ren, Ruolei Hu

引用次数: 0

Retraction of: LINC00265 targets miR-382-5p to regulate SAT1, VAV3 and angiogenesis in osteosarcoma. LINC00265的回缩靶向miR-382-5p调控骨肉瘤中SAT1、VAV3和血管生成。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-01-31 DOI: 10.18632/aging.206195

Ying Xiao, Chunling Li, Hongyue Wang, Yijun Liu

引用次数: 0

Diet, lifestyle and telomere length: using Copula Graphical Models on NHANES data. 饮食、生活方式和端粒长度：在NHANES数据上使用Copula图形模型。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-01-29 DOI: 10.18632/aging.206194

Angelo M Tedaldi, Pariya Behrouzi, Pol Grootswagers

{"title":"Diet, lifestyle and telomere length: using Copula Graphical Models on NHANES data.","authors":"Angelo M Tedaldi, Pariya Behrouzi, Pol Grootswagers","doi":"10.18632/aging.206194","DOIUrl":"10.18632/aging.206194","url":null,"abstract":"Telomere length has been related to human health and ageing in multiple studies. However, these studies have analyzed a small set of variables, according to pre-formulated hypotheses. We used data from NHANES 1999-2002 to perform a preregistered cross-sectional analysis. From these four years we selected the participants with available leukocyte telomere length measure and with plausible daily energy intake, leading to a total study population of 7096 participants. Then, we divided the participants in three groups according to age: Young 20-39 (n = 2623), Middle 40-59 (n = 2210), Old 60-84 (n = 2263). On each group we performed Copula Graphical Modelling (CGM) to capture the links between the variables of interest, and we conducted certainty and sensitivity analyses to understand the robustness of the results. Blood levels of C-reactive protein and γ-tocopherol, and intake of caffeine and fibers are inversely related to telomere length across the age strata. Sex, race, smoking, physical activity and indicators of socioeconomic status have almost no direct connection with telomeres; however, they are directly linked to C-reactive protein, which in turn is connected to leukocyte telomere length. C-reactive protein is therefore a possible central mediator of the effect of these factors on telomeres.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"17 ","pages":"329-356"},"PeriodicalIF":3.9,"publicationDate":"2025-01-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892917/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143069657","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Age-invariant genes: multi-tissue identification and characterization of murine reference genes. 年龄不变基因：小鼠内参基因的多组织鉴定和表征。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-01-27 DOI: 10.18632/aging.206192

John T González, Kyra Thrush-Evensen, Margarita Meer, Morgan E Levine, Albert T Higgins-Chen

{"title":"Age-invariant genes: multi-tissue identification and characterization of murine reference genes.","authors":"John T González, Kyra Thrush-Evensen, Margarita Meer, Morgan E Levine, Albert T Higgins-Chen","doi":"10.18632/aging.206192","DOIUrl":"10.18632/aging.206192","url":null,"abstract":"Studies of the aging transcriptome focus on genes that change with age. But what can we learn from age-invariant genes-those that remain unchanged throughout the aging process? These genes also have a practical application: they can serve as reference genes in expression studies. Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan. Here, we build upon a common pipeline for identifying reference genes in RNA-seq datasets to identify age-invariant genes across seventeen C57BL/6 mouse tissues (brain, lung, bone marrow, muscle, white blood cells, heart, small intestine, kidney, liver, pancreas, skin, brown, gonadal, marrow, and subcutaneous adipose tissue) spanning 1 to 21+ months of age. We identify 9 pan-tissue age-invariant genes, and many tissue-specific age-invariant genes. These genes are stable across the lifespan and are validated in independent bulk RNA-seq datasets and RT-qPCR. Age-invariant genes have shorter transcripts and are enriched for CpG islands. Interestingly, pathway enrichment analysis for age-invariant genes identifies an overrepresentation of molecular functions associated with some, but not all, hallmarks of aging. Thus, even though hallmarks of aging typically involve change, select genes associated with these hallmarks resist age-related change. Finally, our analysis provides a list of murine tissues where classical reference genes are appropriate for application in aging studies. However, no classical reference gene is appropriate across all aging tissues. Instead, we provide novel tissue-specific and pan-tissue reference genes for assays utilizing gene normalization (RT-qPCR) that can be applied to mice across the lifespan.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"170-202"},"PeriodicalIF":3.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810070/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143054346","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oct4, Sox2, Klf4, c-My (OSKM) gene therapy in the hypothalamus prolongs fertility and ovulation in female rats. 下丘脑Oct4， Sox2, Klf4, c-My （OSKM）基因治疗可延长雌性大鼠的生育和排卵。

IF 3.9 3区医学

Aging-Us Pub Date : 2025-01-24 DOI: 10.18632/aging.206191

Maria D Gallardo, Mauricio Girard, Enrique L Portiansky, Rodolfo G Goya

{"title":"Oct4, Sox2, Klf4, c-My (OSKM) gene therapy in the hypothalamus prolongs fertility and ovulation in female rats.","authors":"Maria D Gallardo, Mauricio Girard, Enrique L Portiansky, Rodolfo G Goya","doi":"10.18632/aging.206191","DOIUrl":"10.18632/aging.206191","url":null,"abstract":"In middle-aged (MA) female rats, we have demonstrated that intrahypothalamic gene therapy for insulin-like growth factor-I (IGF-I) extends the regular cyclicity of the animals beyond 10 months (the age at which MA rats stop ovulating). Here, we implemented long-term OSKM gene therapy in the hypothalamus of young female rats. The main goal was to extend fertility in the treated animals. We constructed an adenovector that harbors the GFP gene as well as 4 Yamanaka genes. An adenovector that only carries the gene for GFP or DsRed was used as control. At 4 months of age 12 female rats received an intrahypothalamic injection of our OSKM vector (treated rats); 12 control rats received a vector expressing a marker gene (control rats). At 9.3 months of age control and treated rats were mated with young males. A group of 12 young intact female rats was also mated. The rate of pregnancy recorded was 83%, 8.3 and 25% for young, MA control and MA treated animals, respectively. Pup body weight (BW) at weaning was significantly higher in the MA OSKM rats than in MA controls. At the age of estropause (10 months), OSKM treated females still showed regular estrous cycles. The particular significance of the present results is that, for the first time, it is shown that long-term OSKM gene therapy in the hypothalamus is able to extend the functionality of such a complex system as the hypothalamo-pituitary-ovarian axis.","PeriodicalId":55547,"journal":{"name":"Aging-Us","volume":"null ","pages":"161-169"},"PeriodicalIF":3.9,"publicationDate":"2025-01-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11810065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0