Epigenetic Predictor of Age
Sven Bocklandt,Wen Lin,Mary E. Sehl,Francisco J. Sánchez,Janet S. Sinsheimer,Steve Horvath,Eric Vilain +6 more
TLDR
A measurement of relevant sites in the genome could be a tool in routine medical screening to predict the risk of age-related diseases and to tailor interventions based on the epigenetic bio-age instead of the chronological age.Abstract:
From the moment of conception, we begin to age. A decay of cellular structures, gene regulation, and DNA sequence ages cells and organisms. DNA methylation patterns change with increasing age and contribute to age related disease. Here we identify 88 sites in or near 80 genes for which the degree of cytosine methylation is significantly correlated with age in saliva of 34 male identical twin pairs between 21 and 55 years of age. Furthermore, we validated sites in the promoters of three genes and replicated our results in a general population sample of 31 males and 29 females between 18 and 70 years of age. The methylation of three sites—in the promoters of the EDARADD, TOM1L1, and NPTX2 genes—is linear with age over a range of five decades. Using just two cytosines from these loci, we built a regression model that explained 73% of the variance in age, and is able to predict the age of an individual with an average accuracy of 5.2 years. In forensic science, such a model could estimate the age of a person, based on a biological sample alone. Furthermore, a measurement of relevant sites in the genome could be a tool in routine medical screening to predict the risk of age-related diseases and to tailor interventions based on the epigenetic bio-age instead of the chronological age.read more
Citations
More filters
Journal ArticleDOI
DNA methylation age of human tissues and cell types
TL;DR: It is proposed that DNA methylation age measures the cumulative effect of an epigenetic maintenance system, and can be used to address a host of questions in developmental biology, cancer and aging research.
Journal ArticleDOI
DNA methylation arrays as surrogate measures of cell mixture distribution
Eugene Andres Houseman,William P. Accomando,Devin C. Koestler,Brock C. Christensen,Carmen J. Marsit,Heather H. Nelson,John K. Wiencke,Karl T. Kelsey +7 more
TL;DR: This work presents a method, similar to regression calibration, for inferring changes in the distribution of white blood cells between different subpopulations using DNA methylation signatures, in combination with a previously obtained external validation set consisting of signatures from purified leukocyte samples.
Journal ArticleDOI
Genome-wide Methylation Profiles Reveal Quantitative Views of Human Aging Rates
Gregory Hannum,Justin Guinney,Ling Zhao,Ling Zhao,Li Zhang,Guy Hughes,Srinivas R. Sadda,Brandy Klotzle,Marina Bibikova,Jian-Bing Fan,Yuan Gao,Rob Deconde,Menzies Chen,Indika Rajapakse,Stephen H. Friend,Trey Ideker,Kang Zhang,Kang Zhang +17 more
TL;DR: A quantitative model of aging is built using measurements at more than 450,000 CpG markers from the whole blood of 656 human individuals, aged 19 to 101, to measure the rate at which an individual's methylome ages, which is impacted by gender and genetic variants.
Journal ArticleDOI
DNA methylation-based biomarkers and the epigenetic clock theory of ageing
Steve Horvath,Ken Raj +1 more
TL;DR: Biomarkers of ageing based on DNA methylation data enable accurate age estimates for any tissue across the entire life course and link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course.
Journal ArticleDOI
Inflammaging: a new immune–metabolic viewpoint for age-related diseases
TL;DR: It is argued that chronic diseases are not only the result of ageing and inflammaging; these diseases also accelerate the ageing process and can be considered a manifestation of accelerated ageing, and the use of new biomarkers capable of assessing biological versus chronological age in metabolic diseases is proposed.
References
More filters
Journal ArticleDOI
WGCNA: an R package for weighted correlation network analysis.
Peter Langfelder,Steve Horvath +1 more
TL;DR: The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis that includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software.
Journal ArticleDOI
Statistical significance for genomewide studies
John D. Storey,Robert Tibshirani +1 more
TL;DR: This work proposes an approach to measuring statistical significance in genomewide studies based on the concept of the false discovery rate, which offers a sensible balance between the number of true and false positives that is automatically calibrated and easily interpreted.
Journal ArticleDOI
Adjusting batch effects in microarray expression data using empirical Bayes methods
TL;DR: This paper proposed parametric and non-parametric empirical Bayes frameworks for adjusting data for batch effects that is robust to outliers in small sample sizes and performs comparable to existing methods for large samples.
Journal ArticleDOI
A General Framework for Weighted Gene Co-Expression Network Analysis
Bin Zhang,Steve Horvath +1 more
TL;DR: A general framework for `soft' thresholding that assigns a connection weight to each gene pair is described and several node connectivity measures are introduced and provided empirical evidence that they can be important for predicting the biological significance of a gene.
Journal ArticleDOI
Epigenetic differences arise during the lifetime of monozygotic twins
Mario F. Fraga,Esteban Ballestar,Maria F. Paz,Santiago Ropero,Fernando Setien,Maria Luisa Ballestar,Damia Heine-Suñer,Juan C. Cigudosa,Miguel Urioste,Javier Benitez,Manuel Boix-Chornet,Abel Sánchez-Aguilera,Charlotte Ling,Emma Carlsson,Pernille Poulsen,Allan Vaag,Zarko Stephan,Tim D. Spector,Yue Zhong Wu,Christoph Plass,Manel Esteller +20 more
TL;DR: Older monozygous twins exhibited remarkable differences in their overall content and genomic distribution of 5-methylcytosine DNA and histone acetylation, affecting their gene-expression portrait, indicating how an appreciation of epigenetics is missing from the understanding of how different phenotypes can be originated from the same genotype.
Related Papers (5)
DNA methylation age of blood predicts all-cause mortality in later life.
Riccardo E. Marioni,Riccardo E. Marioni,Sonia Shah,Allan F. McRae,Brian H. Chen,Elena Colicino,Sarah E. Harris,Jude Gibson,Anjali K. Henders,Paul Redmond,Simon R. Cox,Alison Pattie,Janie Corley,Lee Murphy,Nicholas G. Martin,Grant W. Montgomery,Andrew P. Feinberg,M. Daniele Fallin,M. Daniele Fallin,Michael L. Multhaup,Andrew E. Jaffe,Roby Joehanes,Roby Joehanes,Joel Schwartz,Allan C. Just,Kathryn L. Lunetta,Kathryn L. Lunetta,Joanne M. Murabito,Joanne M. Murabito,John M. Starr,Steve Horvath,Andrea A. Baccarelli,Daniel Levy,Peter M. Visscher,Peter M. Visscher,Naomi R. Wray,Ian J. Deary +36 more
Epigenetic differences arise during the lifetime of monozygotic twins
Mario F. Fraga,Esteban Ballestar,Maria F. Paz,Santiago Ropero,Fernando Setien,Maria Luisa Ballestar,Damia Heine-Suñer,Juan C. Cigudosa,Miguel Urioste,Javier Benitez,Manuel Boix-Chornet,Abel Sánchez-Aguilera,Charlotte Ling,Emma Carlsson,Pernille Poulsen,Allan Vaag,Zarko Stephan,Tim D. Spector,Yue Zhong Wu,Christoph Plass,Manel Esteller +20 more