An epigenetic biomarker of aging for lifespan and healthspan

Morgan E. Levine(University of California, Los Angeles), Ake T. Lu(University of California, Los Angeles), Austin Quach(University of California, Los Angeles), Brian H. Chen(National Institutes of Health), Themistocles L. Assimes(Stanford University), Stefania Bandinelli(Azienda Usl Toscana Centro), Lifang Hou(Robert H. Lurie Comprehensive Cancer Center of Northwestern University), Andrea Baccarelli(Columbia University), James D. Stewart(University of North Carolina at Chapel Hill), Yun Li(University of North Carolina at Chapel Hill), Eric A. Whitsel(University of North Carolina at Chapel Hill), James G. Wilson(University of Mississippi Medical Center), Alex P. Reiner(Fred Hutch Cancer Center), Abraham Aviv(Rutgers New Jersey Medical School), Kurt Lohman(Rutgers, The State University of New Jersey), Ching‐Ti Liu(Wake Forest University), Luigi Ferrucci(National Institute on Aging), Steve Horvath(University of California, Los Angeles)
Aging
April 18, 2018
10.18632/aging.101414
Cited by 3,499Open Access
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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.

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