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. Reiner1, Abraham Aviv1, Kurt Lohman, Yongmei Liu, Luigi Ferrucci, Steve Horvath*

*Corresponding author for this work

Research output: Contribution to journalArticle

124 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)573-591
Number of pages19
JournalAging
Volume10
Issue number4
DOIs
StatePublished - Apr 1 2018

Fingerprint

Epigenomics
Biomarkers
Interferons
Transcriptional Activation
DNA Damage
Alzheimer Disease
Mortality
Neoplasms

Keywords

  • Biomarker
  • DNA methylation
  • Epigenetic clock
  • Healthspan

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Levine, M. E., Lu, A. T., Quach, A., Chen, B. H., Assimes, T. L., Bandinelli, S., ... Horvath, S. (2018). An epigenetic biomarker of aging for lifespan and healthspan. Aging, 10(4), 573-591. https://doi.org/10.18632/aging.101414
Levine, Morgan E. ; Lu, Ake T. ; Quach, Austin ; Chen, Brian H. ; Assimes, Themistocles L. ; Bandinelli, Stefania ; Hou, Lifang ; Baccarelli, Andrea A. ; Stewart, James D. ; Li, Yun ; Whitsel, Eric A. ; Wilson, James G. ; Reiner1, Alex P. ; Aviv1, Abraham ; Lohman, Kurt ; Liu, Yongmei ; Ferrucci, Luigi ; Horvath, Steve. / An epigenetic biomarker of aging for lifespan and healthspan. In: Aging. 2018 ; Vol. 10, No. 4. pp. 573-591.
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Levine, ME, Lu, AT, Quach, A, Chen, BH, Assimes, TL, Bandinelli, S, Hou, L, Baccarelli, AA, Stewart, JD, Li, Y, Whitsel, EA, Wilson, JG, Reiner1, AP, Aviv1, A, Lohman, K, Liu, Y, Ferrucci, L & Horvath, S 2018, 'An epigenetic biomarker of aging for lifespan and healthspan', Aging, vol. 10, no. 4, pp. 573-591. https://doi.org/10.18632/aging.101414

An epigenetic biomarker of aging for lifespan and healthspan. / Levine, Morgan E.; Lu, Ake T.; Quach, Austin; Chen, Brian H.; Assimes, Themistocles L.; Bandinelli, Stefania; Hou, Lifang; Baccarelli, Andrea A.; Stewart, James D.; Li, Yun; Whitsel, Eric A.; Wilson, James G.; Reiner1, Alex P.; Aviv1, Abraham; Lohman, Kurt; Liu, Yongmei; Ferrucci, Luigi; Horvath, Steve.

In: Aging, Vol. 10, No. 4, 01.04.2018, p. 573-591.

Research output: Contribution to journalArticle

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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.

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KW - Biomarker

KW - DNA methylation

KW - Epigenetic clock

KW - Healthspan

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Levine ME, Lu AT, Quach A, Chen BH, Assimes TL, Bandinelli S et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging. 2018 Apr 1;10(4):573-591. https://doi.org/10.18632/aging.101414