An Epigenetic Biomarker of Aging for Lifespan and Healthspan

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2018 Apr 21

PMID 29676998

Citations 1250

Authors

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

Affiliations

Soon will be listed here.

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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