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

By Steve Horvath, J. Oshima, G. Martin, A. Lu, Austin Quach, Howard Cohen, Sarah Felton, Mieko Matsuyama, Donna J. Lowe, S. Kabacik and 13 more. Aging, 2018

681 citations recorded by the source corpus.

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.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/5aea831bcbe47eac49733ca7d77152ab9dd53e11

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In Molecular Biology

Citations in the corpus

DNA methylation aging clocks: challenges and recommendations (2019, background): “The benefit of bespoke clocks is seen in the recent “Skin-Blood” clock, devised due to poor performance of the Horvath clock in estimating advanced age in Hutchinson-Gilford progeria syndrome, potentially due to cultured fibroblasts being incorrectly calibrated [64].”