A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking.
Nat Aging
; 2(7): 644-661, 2022 07.
Article
em En
| MEDLINE
| ID: mdl-36277076
ABSTRACT
Epigenetic clocks are widely used aging biomarkers calculated from DNA methylation data, but this data can be surprisingly unreliable. Here we show technical noise produces deviations up to 9 years between replicates for six prominent epigenetic clocks, limiting their utility. We present a computational solution to bolster reliability, calculating principal components from CpG-level data as input for biological age prediction. Our retrained principal-component versions of six clocks show agreement between most replicates within 1.5 years, improved detection of clock associations and intervention effects, and reliable longitudinal trajectories in vivo and in vitro. This method entails only one additional step compared to traditional clocks, requires no replicates or prior knowledge of CpG reliabilities for training, and can be applied to any existing or future epigenetic biomarker. The high reliability of principal component-based clocks is critical for applications to personalized medicine, longitudinal tracking, in vitro studies, and clinical trials of aging interventions.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Metilação de DNA
/
Epigênese Genética
Tipo de estudo:
Risk_factors_studies
Idioma:
En
Revista:
Nat Aging
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Estados Unidos