An epigenetic biomarker of aging for lifespan and healthspan
Top Cited Papers
Open Access
- 18 April 2018
- journal article
- research article
- Published by Impact Journals, LLC in Aging
- Vol. 10 (4), 573-591
- https://doi.org/10.18632/aging.101414
Abstract
Identifying reliable biomarkers of aging is a major goal in geroscience. While the first generation of epigenetic biomarkers of aging were developed using chronological age as a surrogate for biological age, we hypothesized that incorporation of composite clinical measures of phenotypic age that capture differences in lifespan and healthspan may identify novel CpGs and facilitate the development of a more powerful epigenetic biomarker of aging. Using an innovative two-step process, we develop a new epigenetic biomarker of aging, DNAm PhenoAge 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. While this biomarker was developed using data from whole blood, it correlates strongly with age in every tissue and cell tested. Based on an in-depth transcriptional analysis in sorted cells, we find that increased epigenetic, relative to chronological age, is associated with increased activation of pro-inflammatory and interferon pathways, and decreased activation of transcriptional/translational machinery, DNA damage response, and mitochondrial signatures. Overall, this single epigenetic biomarker of aging is able to capture risks for an array of diverse outcomes across multiple tissues and cells, and provide insight into important pathways in aging.Keywords
This publication has 62 references indexed in Scilit:
- Genome maintenance and transcription integrity in aging and diseaseFrontiers in Genetics, 2013
- DNA methylation age of human tissues and cell typesGenome Biology, 2013
- DNA methylation arrays as surrogate measures of cell mixture distributionBMC Bioinformatics, 2012
- Tobacco-Smoking-Related Differential DNA Methylation: 27K Discovery and ReplicationAmerican Journal of Human Genetics, 2011
- GCTA: A Tool for Genome-wide Complex Trait AnalysisAmerican Journal of Human Genetics, 2011
- Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancerGenome Research, 2010
- Human aging-associated DNA hypermethylation occurs preferentially at bivalent chromatin domainsGenome Research, 2010
- Evolution of the human lifespan and diseases of aging: Roles of infection, inflammation, and nutritionProceedings of the National Academy of Sciences of the United States of America, 2009
- Persistent transcription-blocking DNA lesions trigger somatic growth attenuation associated with longevityNature, 2009
- Genetic analysis of ageing: role of oxidative damage and environmental stressesNature Genetics, 1996