DNA methylation age of human tissues and cell types
TLDR
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.Abstract:
It is not yet known whether DNA methylation levels can be used to accurately predict age across a broad spectrum of human tissues and cell types, nor whether the resulting age prediction is a biologically meaningful measure. I developed a multi-tissue predictor of age that allows one to estimate the DNA methylation age of most tissues and cell types. The predictor, which is freely available, was developed using 8,000 samples from 82 Illumina DNA methylation array datasets, encompassing 51 healthy tissues and cell types. I found that DNA methylation age has the following properties: first, it is close to zero for embryonic and induced pluripotent stem cells; second, it correlates with cell passage number; third, it gives rise to a highly heritable measure of age acceleration; and, fourth, it is applicable to chimpanzee tissues. Analysis of 6,000 cancer samples from 32 datasets showed that all of the considered 20 cancer types exhibit significant age acceleration, with an average of 36 years. Low age-acceleration of cancer tissue is associated with a high number of somatic mutations and TP53 mutations, while mutations in steroid receptors greatly accelerate DNA methylation age in breast cancer. Finally, I characterize the 353 CpG sites that together form an aging clock in terms of chromatin states and tissue variance. I propose that DNA methylation age measures the cumulative effect of an epigenetic maintenance system. This novel epigenetic clock can be used to address a host of questions in developmental biology, cancer and aging research.read more
Citations
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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.
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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.
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Multi-omics approaches to disease.
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An epigenetic biomarker of aging for lifespan and healthspan
Morgan E. Levine,Ake T. Lu,Austin Quach,Brian H. Chen,Themistocles L. Assimes,Stefania Bandinelli,Lifang Hou,Andrea A. Baccarelli,James D. Stewart,Yun Li,Eric A. Whitsel,James G. Wilson,Alex P. Reiner,Abraham Aviv,Kurt Lohman,Yongmei Liu,Luigi Ferrucci,Steve Horvath +17 more
TL;DR: A new epigenetic biomarker of aging, DNAm PhenoAge, is developed that strongly outperforms previous measures in regards to predictions for a variety of aging outcomes, including all-cause mortality, cancers, healthspan, physical functioning, and Alzheimer's disease.
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Senescence in Health and Disease
Shenghui He,Norman E. Sharpless +1 more
TL;DR: This model suggests that the abundance of senescent cells in vivo predicts "molecular," as opposed to chronologic, age and that senescent cell clearance may mitigate aging-associated pathology.
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