Experimental Gerontology最新文献

英文中文

A mathematical model which examines age-related stochastic fluctuations in DNA maintenance methylation 一个数学模型，检验年龄相关的DNA维持甲基化随机波动

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2021-02-06 DOI: 10.1101/2021.02.05.429896

L. Zagkos, Jason Roberts, M. M. Auley

Due to its complexity and its ubiquitous nature the ageing process remains an enduring biological puzzle. Many molecular mechanisms and biochemical process have become synonymous with ageing. However, recent findings have pinpointed epigenetics as having a key role in ageing and healthspan. In particular age related changes to DNA methylation offer the possibility of monitoring the trajectory of biological ageing and could even be used to predict the onset of diseases such as cancer, Alzheimer’s disease and cardiovascular disease. At the molecular level emerging evidence strongly suggests the regulatory processes which govern DNA methylation are subject to intracellular stochasticity. It is challenging to fully understand the impact of stochasticity on DNA methylation levels at the molecular level experimentally. An ideal solution is to use mathematical models to capture the essence of the stochasticity and its outcomes. In this paper we present a novel stochastic model which accounts for specific methylation levels within a gene promoter. We quantify the uncertainty of the eventual cite-specific methylation levels for different values of methylation age, depending on the initial methylation levels. Our model predicts the observed bistable levels in CpG islands. In addition, simulations with various levels of noise indicate that uncertainty predominantly spreads through the hypermethylated region of stability, especially for large values of input noise. A key outcome of the model is that CpG islands with intermediate methylation levels tend to be more susceptible to dramatic DNA methylation changes towards both hypomethylation and hypermethylation, due to increasing methylation age.

由于其复杂性和普遍性，衰老过程仍然是一个持久的生物学难题。许多分子机制和生化过程已成为衰老的代名词。然而，最近的研究发现，表观遗传学在衰老和健康寿命中起着关键作用。特别是与年龄相关的DNA甲基化变化提供了监测生物衰老轨迹的可能性，甚至可以用来预测癌症、阿尔茨海默病和心血管疾病等疾病的发病。在分子水平上，新出现的证据强烈表明，控制DNA甲基化的调控过程受细胞内随机性的影响。在分子水平上，从实验上充分理解随机性对DNA甲基化水平的影响具有挑战性。一个理想的解决方案是使用数学模型来捕捉随机性及其结果的本质。在本文中，我们提出了一个新的随机模型，该模型可以解释基因启动子内特定的甲基化水平。根据初始甲基化水平，我们量化了不同甲基化年龄值的最终引物特异性甲基化水平的不确定性。我们的模型预测了在CpG岛屿上观测到的双稳态水平。此外，具有不同噪声水平的模拟表明，不确定性主要通过稳定性的高甲基化区域传播，特别是对于大值的输入噪声。该模型的一个关键结果是，由于甲基化年龄的增加，具有中等甲基化水平的CpG岛往往更容易受到DNA甲基化向低甲基化和高甲基化方向变化的影响。

{"title":"A mathematical model which examines age-related stochastic fluctuations in DNA maintenance methylation","authors":"L. Zagkos, Jason Roberts, M. M. Auley","doi":"10.1101/2021.02.05.429896","DOIUrl":"https://doi.org/10.1101/2021.02.05.429896","url":null,"abstract":"Due to its complexity and its ubiquitous nature the ageing process remains an enduring biological puzzle. Many molecular mechanisms and biochemical process have become synonymous with ageing. However, recent findings have pinpointed epigenetics as having a key role in ageing and healthspan. In particular age related changes to DNA methylation offer the possibility of monitoring the trajectory of biological ageing and could even be used to predict the onset of diseases such as cancer, Alzheimer’s disease and cardiovascular disease. At the molecular level emerging evidence strongly suggests the regulatory processes which govern DNA methylation are subject to intracellular stochasticity. It is challenging to fully understand the impact of stochasticity on DNA methylation levels at the molecular level experimentally. An ideal solution is to use mathematical models to capture the essence of the stochasticity and its outcomes. In this paper we present a novel stochastic model which accounts for specific methylation levels within a gene promoter. We quantify the uncertainty of the eventual cite-specific methylation levels for different values of methylation age, depending on the initial methylation levels. Our model predicts the observed bistable levels in CpG islands. In addition, simulations with various levels of noise indicate that uncertainty predominantly spreads through the hypermethylated region of stability, especially for large values of input noise. A key outcome of the model is that CpG islands with intermediate methylation levels tend to be more susceptible to dramatic DNA methylation changes towards both hypomethylation and hypermethylation, due to increasing methylation age.","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2021-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45725598","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: 3

WITHDRAWN: Regular exercise protects aging Drosophila from high-fat-diet-induced locomotor impairment, cardiac dysfunction, lifespan shortening, and Nmnat and dSir2 expression decline. 撤回：经常锻炼可保护衰老果蝇免受高脂饮食引起的运动损伤、心脏功能障碍、寿命缩短以及Nmnat和dSir2表达下降的影响。

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2018-01-31 DOI: 10.1016/j.exger.2018.01.017

Deng-Tai Wen, Lan Zheng, Fan Yang, Han-Zhe Li, Jing Chen, Jin-Xiu Li, Dan Cheng, Kai Lu, Yang Liu, Xian-Chu Liu, Wen-Qi Hou

This article has been withdrawn at the request of the author(s) and/or editor. The Publisher apologizes for any inconvenience this may cause. The full Elsevier Policy on Article Withdrawal can be found at https://www.elsevier.com/about/our-business/policies/article-withdrawal.

应作者和/或编辑的要求，本文已被撤回。出版商对此造成的不便深表歉意。完整的爱思唯尔文章撤稿政策请访问 https://www.elsevier.com/about/our-business/policies/article-withdrawal。

引用次数: 0

WITHDRAWN: Serum uric acid and prevalence of age-related hearing loss in the Japanese population: Baseline data from the Aidai Cohort Study in Yawatahama. 撤回：日本人血清尿酸与老年性听力损失的患病率：来自八幡浜爱台队列研究的基线数据。

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2018-01-12 DOI: 10.1016/j.exger.2017.12.027

Daiki Takagi, Shinya Furukawa, Masahiro Okada, Keiko Tanaka, Hidenori Senba, Masato Teraoka, Hiroyuki Yamada, Naohito Hato, Yoshihiro Miyake

引用次数: 0

Over het Nihilisme : Nietzsches actualiteit of de onze? 关于虚无主义:尼采的现状还是我们的?

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2017-04-03 DOI: 10.17159/2224-7912/2017/V57N1A5

P. V. Tongeren

On Nihilism: Nietzsche’s “Here and now” or our own?If philosophy claims to be an analysis of the here and now, it should also reflect on the preconditions of a description and diagnosis of the present. One of the challenges presented by such an analysis is the risk of repeating the prejudices of the present in the description thereof. In this article, I attempt to address this challenge by presenting Nietzsche’s description and interpretation of nihilism in such a way that the topicality of that description comes to light.Nietzsche distinguishes at least three different stages or forms of nihilism. The first one is also called pessimism, or more precisely: the pessimism of the tragic Greeks. It is an awareness of the absurdity of life and reality without becoming completely befuddled by it. The history of European culture from Socrates up to Nietzsche’s 19th century is the period in which a second form of nihilism emerges. Unable to affirm the absurdity of reality, people started to devalue it and to interpret it in the light of a truer reality. This ultimate reality was conceived as meaningful and intelligible, and it showed the reality of our sensual experience to be unreal, only apparent and contingent. This schema is nihilistic because it denies the reality of our sensual world. It was introduced first and foremost by Plato’s philosophy and then “democratized” in Christianity. But it dominated all of European culture (science, morality, religion and art) for 2500 years. The third stage or form of nihilism is associated with “the death of God”, i.e. the erosion and eventual demise of the core concept upholding the protective structure that was built by the second phase of nihilism. The death of God is what Nietzsche foresees as coming to pass in the two centuries to come. His theory of nihilism is a description of this future. It proves not to be too difficult to present Nietzsche’s description of this future in such a way that we recognize our present.

论虚无主义:尼采的“此时此地”还是我们自己的?如果哲学自称是对此时此地的分析，那么它也应当反思对现在的描述和诊断的前提条件。这种分析提出的挑战之一是，在对其进行描述时可能会重复当前的偏见。在这篇文章中，我试图通过呈现尼采对虚无主义的描述和解释来解决这个挑战，以一种描述的话题性被揭示出来的方式。尼采区分了虚无主义至少三个不同的阶段或形式。第一种也被称为悲观主义，或者更准确地说，是悲剧的希腊人的悲观主义。它是一种对生活和现实的荒谬的认识，而不被它完全迷惑。从苏格拉底到尼采的19世纪，欧洲文化史是第二种虚无主义出现的时期。由于无法肯定现实的荒谬，人们开始贬低它，并根据更真实的现实来解释它。这个终极现实被认为是有意义的和可理解的，它表明我们感官经验的现实是不真实的，只是明显的和偶然的。这种图式是虚无主义的，因为它否认了我们感官世界的现实。它首先是由柏拉图的哲学引入的，然后在基督教中“民主化”。但它统治了整个欧洲文化(科学、道德、宗教和艺术)2500年。虚无主义的第三阶段或形式与“上帝之死”有关，即支撑虚无主义第二阶段所建立的保护结构的核心概念的侵蚀和最终消亡。上帝之死是尼采所预见的，将在未来两个世纪发生。他的虚无主义理论就是对这种未来的描述。事实证明，用一种我们认识到现在的方式来呈现尼采对未来的描述并不太难。

{"title":"Over het Nihilisme : Nietzsches actualiteit of de onze?","authors":"P. V. Tongeren","doi":"10.17159/2224-7912/2017/V57N1A5","DOIUrl":"https://doi.org/10.17159/2224-7912/2017/V57N1A5","url":null,"abstract":"On Nihilism: Nietzsche’s “Here and now” or our own?If philosophy claims to be an analysis of the here and now, it should also reflect on the preconditions of a description and diagnosis of the present. One of the challenges presented by such an analysis is the risk of repeating the prejudices of the present in the description thereof. In this article, I attempt to address this challenge by presenting Nietzsche’s description and interpretation of nihilism in such a way that the topicality of that description comes to light.Nietzsche distinguishes at least three different stages or forms of nihilism. The first one is also called pessimism, or more precisely: the pessimism of the tragic Greeks. It is an awareness of the absurdity of life and reality without becoming completely befuddled by it. The history of European culture from Socrates up to Nietzsche’s 19th century is the period in which a second form of nihilism emerges. Unable to affirm the absurdity of reality, people started to devalue it and to interpret it in the light of a truer reality. This ultimate reality was conceived as meaningful and intelligible, and it showed the reality of our sensual experience to be unreal, only apparent and contingent. This schema is nihilistic because it denies the reality of our sensual world. It was introduced first and foremost by Plato’s philosophy and then “democratized” in Christianity. But it dominated all of European culture (science, morality, religion and art) for 2500 years. The third stage or form of nihilism is associated with “the death of God”, i.e. the erosion and eventual demise of the core concept upholding the protective structure that was built by the second phase of nihilism. The death of God is what Nietzsche foresees as coming to pass in the two centuries to come. His theory of nihilism is a description of this future. It proves not to be too difficult to present Nietzsche’s description of this future in such a way that we recognize our present.","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2017-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45480702","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

Ageing is not associated with an altered immune response during Trypanosoma cruzi infection Ageing and Trypanosoma cruzi infection 衰老与克氏锥虫感染期间免疫反应的改变无关

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2017-04-01 DOI: 10.1016/j.exger.2017.01.022

R. P. Colato, Vânia Brazão, F. H. Santello, M. Toldo, Gabriel Tavares Vale, C. Tirapelli, G. Pereira-da-Silva, J. Prado

引用次数: 3

Amyloid precursor protein expression is enhanced in human platelets from subjects with Alzheimer's disease and frontotemporal lobar degeneration: a real-time PCR study. 淀粉样蛋白前体蛋白在阿尔茨海默病和额颞叶变性患者的血小板中表达增强:一项实时PCR研究

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2013-12-01

Arianna Vignini, Stefano Morganti, Eleonora Salvolini, Davide Sartini, Simona Luzzi, Rosamaria Fiorini, Leandro Provinciali, Roberto Di Primio, Laura Mazzanti, Monica Emanuelli

Frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) represent the most frequent causes of early-onset and late-onset degenerative dementia, respectively. A correct diagnosis entails the choice of appropriate therapies. In this view the present study aimed to identify biomarkers that could improve the differential diagnosis. We recently found an overexpression of platelet amyloid precursor protein (APP) in AD; furthermore, recent studies have suggested the presence of changes in APP processing in FTLD. In this context, we analyzed the mRNA expression level of Total APP (TOT) and APP containing a Kunitz-type serine protease inhibitor domain (KPI) in platelets obtained from AD patients, subjects with FTLD, and healthy subjects. In addition, we evaluated the correlation between platelet APP mRNA expression levels and cognitive impairment.Differential gene expression measurements revealed a significant up-regulation of APP TOT and APP KPI in both AD and FTLD patients compared to the controls (being AD/Controls: 1.67 for APP TOT and 1.47 for APP KPI; FTLD/Controls: 1.62 for APP TOT and 1.51 for APP KPI; p < 0.05), although it is interesting to note that in FTLD patients this expression did not correlate with the severity of cognitive impairment.This could be related to a reduced beta-amyloid (Aβ) formation, caused by an alteration of secretase enzymatic activity, even though a post-transcriptional regulation of APP mRNAs in FTLD cannot be excluded.

额颞叶变性(FTLD)和阿尔茨海默病(AD)分别是早发性和晚发性退行性痴呆的最常见原因。正确的诊断需要选择适当的治疗方法。从这个角度来看，本研究旨在确定可以改善鉴别诊断的生物标志物。我们最近发现AD患者血小板淀粉样前体蛋白(APP)过表达;此外，最近的研究表明，在FTLD中存在APP加工的变化。在此背景下，我们分析了AD患者、FTLD患者和健康受试者血小板中总APP (TOT)和含有kuniz型丝氨酸蛋白酶抑制剂结构域(KPI)的APP的mRNA表达水平。此外，我们还评估了血小板APP mRNA表达水平与认知功能障碍的相关性。差异基因表达测量显示，与对照组相比，AD和FTLD患者的APP TOT和APP KPI均显著上调(AD/对照:APP TOT为1.67,APP KPI为1.47;FTLD/Controls: APP TOT 1.62, APP KPI 1.51;p < 0.05)，但有趣的是，在FTLD患者中，这种表达与认知障碍的严重程度无关。这可能与分泌酶活性改变引起的β -淀粉样蛋白(a β)形成减少有关，尽管不能排除FTLD中APP mrna的转录后调控。

{"title":"Amyloid precursor protein expression is enhanced in human platelets from subjects with Alzheimer's disease and frontotemporal lobar degeneration: a real-time PCR study.","authors":"Arianna Vignini, Stefano Morganti, Eleonora Salvolini, Davide Sartini, Simona Luzzi, Rosamaria Fiorini, Leandro Provinciali, Roberto Di Primio, Laura Mazzanti, Monica Emanuelli","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD) represent the most frequent causes of early-onset and late-onset degenerative dementia, respectively. A correct diagnosis entails the choice of appropriate therapies. In this view the present study aimed to identify biomarkers that could improve the differential diagnosis. We recently found an overexpression of platelet amyloid precursor protein (APP) in AD; furthermore, recent studies have suggested the presence of changes in APP processing in FTLD. In this context, we analyzed the mRNA expression level of Total APP (TOT) and APP containing a Kunitz-type serine protease inhibitor domain (KPI) in platelets obtained from AD patients, subjects with FTLD, and healthy subjects. In addition, we evaluated the correlation between platelet APP mRNA expression levels and cognitive impairment.Differential gene expression measurements revealed a significant up-regulation of APP TOT and APP KPI in both AD and FTLD patients compared to the controls (being AD/Controls: 1.67 for APP TOT and 1.47 for APP KPI; FTLD/Controls: 1.62 for APP TOT and 1.51 for APP KPI; p < 0.05), although it is interesting to note that in FTLD patients this expression did not correlate with the severity of cognitive impairment.This could be related to a reduced beta-amyloid (Aβ) formation, caused by an alteration of secretase enzymatic activity, even though a post-transcriptional regulation of APP mRNAs in FTLD cannot be excluded.</p>","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2013-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32008224","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

Proceedings of the Eleventh International Symposium on the Neurobiology and Neuroendocrinology of Aging, July 29-August 3, 2012, Bregenz, Austria. 第十一届神经生物学与神经内分泌学国际学术会议论文集，2012年7月29- 8月3日，奥地利布雷根茨。

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2013-07-01

引用次数: 0

Proceedings and abstracts of the 8th International Symposium on the Neurobiology and Neuroendocrinology of Aging, July 32-28, 2006, Bregenz, Austria. 第八届老年神经生物学和神经内分泌学国际学术研讨会论文集及摘要，2006年7月32-28日，奥地利布雷根茨。

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2007-01-01

引用次数: 0

Proceedings of the Seventh International Symposium on the Neurobiology and Neuroendocrinology of Aging. July 18023, 2004. Bregenz, Austria. 第七届老年神经生物学和神经内分泌学国际研讨会论文集。2004年7月23日。布雷根茨,奥地利。

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2004-11-01

引用次数: 0

Corrigendum to ?In vivo visualization of aging-associated gene transcription: evidence for free radical theory of aging? 6Exp Gerontol 39 (2004) 239?2479 衰老相关基因转录的体内可视化:衰老自由基理论的证据?6Exp Gerontol 39 (2004) 239?2479

IF 3.9 3区医学 Q2 Biochemistry, Genetics and Molecular Biology

Experimental Gerontology

Pub Date : 2004-07-01 DOI: 10.1016/S0531-5565(04)00160-3

Jian Zhang, Jinlu Dai, Yi Lu, Z. Yao, C. O’Brien, J. Murtha, Weici Qi, Daniel E. Hall, S. Manolagas, W. Ershler, E. Keller

引用次数: 0

首页上一页

下一页尾页

类型

全部化学•材料生命科学医学物理工程技术环境•农林材料科学地球科学法学管理学化学环境科学与生态学计算机科学教育学经济学农林科学人文科学生物学数学物理与天体物理心理学综合性期刊其他工业工程理学历史学农学文学信息工程

数据库

全部 ACS Publications Elsevier ieeexplore Springer The Royal Society of Chemistry Wiley

期刊

Experimental Gerontology

全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.

﹀