{"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}
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
{"title":"WITHDRAWN: Regular exercise protects aging Drosophila from high-fat-diet-induced locomotor impairment, cardiac dysfunction, lifespan shortening, and Nmnat and dSir2 expression decline.","authors":"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","doi":"10.1016/j.exger.2018.01.017","DOIUrl":"10.1016/j.exger.2018.01.017","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2018-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35756275","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":"WITHDRAWN: Serum uric acid and prevalence of age-related hearing loss in the Japanese population: Baseline data from the Aidai Cohort Study in Yawatahama.","authors":"Daiki Takagi, Shinya Furukawa, Masahiro Okada, Keiko Tanaka, Hidenori Senba, Masato Teraoka, Hiroyuki Yamada, Naohito Hato, Yoshihiro Miyake","doi":"10.1016/j.exger.2017.12.027","DOIUrl":"10.1016/j.exger.2017.12.027","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2018-01-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"35741580","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":"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}
R. P. Colato, Vânia Brazão, F. H. Santello, M. Toldo, Gabriel Tavares Vale, C. Tirapelli, G. Pereira-da-Silva, J. Prado
{"title":"Ageing is not associated with an altered immune response during Trypanosoma cruzi infection Ageing and Trypanosoma cruzi infection","authors":"R. P. Colato, Vânia Brazão, F. H. Santello, M. Toldo, Gabriel Tavares Vale, C. Tirapelli, G. Pereira-da-Silva, J. Prado","doi":"10.1016/j.exger.2017.01.022","DOIUrl":"https://doi.org/10.1016/j.exger.2017.01.022","url":null,"abstract":"","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2017-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/j.exger.2017.01.022","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43369238","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":"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}
{"title":"Proceedings of the Eleventh International Symposium on the Neurobiology and Neuroendocrinology of Aging, July 29-August 3, 2012, Bregenz, Austria.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2013-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"32142963","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":"Proceedings and abstracts of the 8th International Symposium on the Neurobiology and Neuroendocrinology of Aging, July 32-28, 2006, Bregenz, Austria.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2007-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"27076950","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":"Proceedings of the Seventh International Symposium on the Neurobiology and Neuroendocrinology of Aging. July 18023, 2004. Bregenz, Austria.","authors":"","doi":"","DOIUrl":"","url":null,"abstract":"","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2004-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"24987045","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}
Jian Zhang, Jinlu Dai, Yi Lu, Z. Yao, C. O’Brien, J. Murtha, Weici Qi, Daniel E. Hall, S. Manolagas, W. Ershler, E. Keller
{"title":"Corrigendum to ?In vivo visualization of aging-associated gene transcription: evidence for free radical theory of aging? 6Exp Gerontol 39 (2004) 239?2479","authors":"Jian Zhang, Jinlu Dai, Yi Lu, Z. Yao, C. O’Brien, J. Murtha, Weici Qi, Daniel E. Hall, S. Manolagas, W. Ershler, E. Keller","doi":"10.1016/S0531-5565(04)00160-3","DOIUrl":"https://doi.org/10.1016/S0531-5565(04)00160-3","url":null,"abstract":"","PeriodicalId":12073,"journal":{"name":"Experimental Gerontology","volume":null,"pages":null},"PeriodicalIF":3.9,"publicationDate":"2004-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/S0531-5565(04)00160-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"56235903","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}