Systematic underestimation of the epigenetic clock and age acceleration in older subjects

Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments. Results The model systematically underestimates age in tissue...

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Published in:Genome Biology Vol. 20; no. 1; p. 283
Main Authors: El Khoury, Louis Y., Gorrie-Stone, Tyler, Smart, Melissa, Hughes, Amanda, Bao, Yanchun, Andrayas, Alexandria, Burrage, Joe, Hannon, Eilis, Kumari, Meena, Mill, Jonathan, Schalkwyk, Leonard C.
Format: Journal Article
Language:English
Published: London BioMed Central 17.12.2019
Springer Nature B.V
BMC
Subjects:
Age
Age acceleration
Aging - genetics
Animal Genetics and Genomics
Bioinformatics
Biological Clocks
Biomedical and Life Sciences
Blood
Cerebellum
CpG islands
data collection
Datasets
Deoxyribonucleic acid
DNA
DNA methylation
Epigenesis, Genetic
Epigenetic clock
Epigenetics
Evolutionary Biology
Genetic testing
genome
Human Genetics
Humans
Life Sciences
Microbial Genetics and Genomics
people
Plant Genetics and Genomics
DNA methylation
Age acceleration
Epigenetic clock
ISSN:1474-760X, 1474-7596, 1474-760X
Online Access:Get full text
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Summary:Background The Horvath epigenetic clock is widely used. It predicts age quite well from 353 CpG sites in the DNA methylation profile in unknown samples and has been used to calculate “age acceleration” in various tissues and environments. Results The model systematically underestimates age in tissues from older people. This is seen in all examined tissues but most strongly in the cerebellum and is consistently observed in multiple datasets. Age acceleration is thus age-dependent, and this can lead to spurious associations. The current literature includes examples of association tests with age acceleration calculated in a wide variety of ways. Conclusions The concept of an epigenetic clock is compelling, but caution should be taken in interpreting associations with age acceleration. Association tests of age acceleration should include age as a covariate.
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ISSN:1474-760X
1474-7596
1474-760X
DOI:10.1186/s13059-019-1810-4