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Event


Epigenetic clock and regenerative medicine

CMCB Life Sciences Seminar

Date:12.09.2019, 16:00 - 17:00
Speaker: Prof. Steve Horvath, UCLA, Brain Research Institute
Location: CRTD, ground floor, auditorium left
Host: Dr. Rupert Overall (DZNE)

Abstract

DNA methylation based biomarkers of aging known as collectively as "epigenetic clock" can be used to measure the age of any human tissue, cell type, or fluid that contains DNA. DNA methylation age captures aspects of biological age, e.g. it predicts lifespan and healthspan in large scale epidemiological studies. I will describe several new epigenetic clocks for humans and other mammals. The skin & blood clock (based on 391 CpGs) is tailor-made for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva 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.

Arguably the strongest predictor of lifespan, DNAm GrimAge, is a composite biomarker based on seven DNAm surrogates of plasma protein levels and a DNAm-based estimator of smoking pack-years. Using large-scale validation data from thousands of individuals, we demonstrated that DNAm GrimAge stands out among existing epigenetic clocks in terms of its predictive ability for time-to-death ( P=2.0E-75), time-to-coronary heart disease (P=6.2E-24), time-to-cancer (P=1.3E-12), its strong relationship with computed tomography for fatty liver/excess visceral fat, and age-at-menopause (P=1.6E-12).Recent genomewide association studies of epigenetic age acceleration shed light on the genetic underpinnings of the epigenetic clock (e.g. Lu et al 2016, PMID: 26830004). The epigenetic clock method has been used in several applications including obesity, Down syndrome, cognitive decline, HIV, Parkinson's disease, and centenarians.

5 most important publications

1. Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol. 2013 Oct 21;14(10):R115. PMCID: PMC4015143

2. Horvath S, Raj K DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018 Jun;19(6):371-384. doi: 10.1038/s41576-018-0004-3. PMID: 29643443

3. Lu AT et al (2019) DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019 Jan 21. doi: 10.18632/aging.101684. PMID: 30669119 https://www.aging-us.com/full/101684

4. Lu et al 2018. GWAS of epigenetic aging rates in blood reveals a critical role for TERT. Nat Commun. 2018 Jan 26;9(1):387. doi: 10.1038/s41467-017-02697-5. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5786029/

5. Horvath et al 2018. Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and ex vivo studies. Aging (Albany NY). 2018 Jul 26;10(7):1758-1775. doi: 10.18632/aging.101508 https://www.aging-us.com/full/10/1758

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