Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies

Steve Horvath*, Junko Oshima, George M. Martin, Ake T. Lu, Austin Quach, Howard Cohen, Sarah Felton, Mieko Matsuyama, Donna Lowe, Sylwia Kabacik, James G. Wilson, Alex P. Reiner, Anna Maierhofer, Julia Flunkert, Abraham Aviv, Lifang Hou, Andrea A. Baccarelli, Yun Li, James D. Stewart, Eric A. WhitselLuigi Ferrucci, Shigemi Matsuyama, Kenneth Raj

*Corresponding author for this work

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain, liver, and even bone samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers. Furthermore, this highly sensitive age estimator accurately tracked the dynamic aging of cells cultured ex vivo and revealed that their proliferation is accompanied by a steady increase in epigenetic age. The skin & blood clock predicts lifespan and it relates to many age-related conditions. Overall, this biomarker is expected to become useful for forensic applications (e.g. blood or buccal swabs) and for a quantitative ex vivo human cell aging assay.

Original languageEnglish (US)
Pages (from-to)1758-1775
Number of pages18
JournalAging
Volume10
Issue number7
DOIs
StatePublished - Jul 1 2018

Fingerprint

Progeria
DNA Methylation
Epigenomics
Blood Cells
Biomarkers
Skin
Fibroblasts
Cheek
Cell Aging
Fetal Blood
Keratinocytes
Saliva
Neuroglia
Gestational Age
Cultured Cells
Endothelial Cells
Neurons
Bone and Bones
Liver
Brain

Keywords

  • DNA methylation
  • Epigenetics
  • Fibroblasts
  • Hutchinson-Gilford
  • Progeria

ASJC Scopus subject areas

  • Aging
  • Cell Biology

Cite this

Horvath, S., Oshima, J., Martin, G. M., Lu, A. T., Quach, A., Cohen, H., ... Raj, K. (2018). Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies. Aging, 10(7), 1758-1775. https://doi.org/10.18632/aging.101508
Horvath, Steve ; Oshima, Junko ; Martin, George M. ; Lu, Ake T. ; Quach, Austin ; Cohen, Howard ; Felton, Sarah ; Matsuyama, Mieko ; Lowe, Donna ; Kabacik, Sylwia ; Wilson, James G. ; Reiner, Alex P. ; Maierhofer, Anna ; Flunkert, Julia ; Aviv, Abraham ; Hou, Lifang ; Baccarelli, Andrea A. ; Li, Yun ; Stewart, James D. ; Whitsel, Eric A. ; Ferrucci, Luigi ; Matsuyama, Shigemi ; Raj, Kenneth. / Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies. In: Aging. 2018 ; Vol. 10, No. 7. pp. 1758-1775.
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Horvath, S, Oshima, J, Martin, GM, Lu, AT, Quach, A, Cohen, H, Felton, S, Matsuyama, M, Lowe, D, Kabacik, S, Wilson, JG, Reiner, AP, Maierhofer, A, Flunkert, J, Aviv, A, Hou, L, Baccarelli, AA, Li, Y, Stewart, JD, Whitsel, EA, Ferrucci, L, Matsuyama, S & Raj, K 2018, 'Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies', Aging, vol. 10, no. 7, pp. 1758-1775. https://doi.org/10.18632/aging.101508

Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies. / Horvath, Steve; Oshima, Junko; Martin, George M.; Lu, Ake T.; Quach, Austin; Cohen, Howard; Felton, Sarah; Matsuyama, Mieko; Lowe, Donna; Kabacik, Sylwia; Wilson, James G.; Reiner, Alex P.; Maierhofer, Anna; Flunkert, Julia; Aviv, Abraham; Hou, Lifang; Baccarelli, Andrea A.; Li, Yun; Stewart, James D.; Whitsel, Eric A.; Ferrucci, Luigi; Matsuyama, Shigemi; Raj, Kenneth.

In: Aging, Vol. 10, No. 7, 01.07.2018, p. 1758-1775.

Research output: Contribution to journalArticle

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T1 - Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies

AU - Horvath, Steve

AU - Oshima, Junko

AU - Martin, George M.

AU - Lu, Ake T.

AU - Quach, Austin

AU - Cohen, Howard

AU - Felton, Sarah

AU - Matsuyama, Mieko

AU - Lowe, Donna

AU - Kabacik, Sylwia

AU - Wilson, James G.

AU - Reiner, Alex P.

AU - Maierhofer, Anna

AU - Flunkert, Julia

AU - Aviv, Abraham

AU - Hou, Lifang

AU - Baccarelli, Andrea A.

AU - Li, Yun

AU - Stewart, James D.

AU - Whitsel, Eric A.

AU - Ferrucci, Luigi

AU - Matsuyama, Shigemi

AU - Raj, Kenneth

PY - 2018/7/1

Y1 - 2018/7/1

N2 - DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in ex vivo studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples. High age correlations can also be observed in sorted neurons, glia, brain, liver, and even bone samples. Gestational age correlates with DNAm age in cord blood. When used on fibroblasts from Hutchinson Gilford Progeria Syndrome patients, this age estimator (referred to as the skin & blood clock) uncovered an epigenetic age acceleration with a magnitude that is below the sensitivity levels of other DNAm-based biomarkers. Furthermore, this highly sensitive age estimator accurately tracked the dynamic aging of cells cultured ex vivo and revealed that their proliferation is accompanied by a steady increase in epigenetic age. The skin & blood clock predicts lifespan and it relates to many age-related conditions. Overall, this biomarker is expected to become useful for forensic applications (e.g. blood or buccal swabs) and for a quantitative ex vivo human cell aging assay.

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KW - DNA methylation

KW - Epigenetics

KW - Fibroblasts

KW - Hutchinson-Gilford

KW - Progeria

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