TY - JOUR
T1 - An epigenetic biomarker of aging for lifespan and healthspan
AU - Levine, Morgan E.
AU - Lu, Ake T.
AU - Quach, Austin
AU - Chen, Brian H.
AU - Assimes, Themistocles L.
AU - Bandinelli, Stefania
AU - Hou, Lifang
AU - Baccarelli, Andrea A.
AU - Stewart, James D.
AU - Li, Yun
AU - Whitsel, Eric A.
AU - Wilson, James G.
AU - Reiner1, Alex P.
AU - Aviv1, Abraham
AU - Lohman, Kurt
AU - Liu, Yongmei
AU - Ferrucci, Luigi
AU - Horvath, Steve
PY - 2018/4/1
Y1 - 2018/4/1
N2 - 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.
AB - 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.
KW - Biomarker
KW - DNA methylation
KW - Epigenetic clock
KW - Healthspan
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UR - http://www.scopus.com/inward/citedby.url?scp=85046851006&partnerID=8YFLogxK
U2 - 10.18632/aging.101414
DO - 10.18632/aging.101414
M3 - Article
C2 - 29676998
AN - SCOPUS:85046851006
VL - 10
SP - 573
EP - 591
JO - Aging
JF - Aging
SN - 1945-4589
IS - 4
ER -