GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality

Abstract The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are hi...

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Veröffentlicht in:The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2021-05, Vol.76 (5), p.741-749
Hauptverfasser: McCrory, Cathal, Fiorito, Giovanni, Hernandez, Belinda, Polidoro, Silvia, O’Halloran, Aisling M, Hever, Ann, Ni Cheallaigh, Cliona, Lu, Ake T, Horvath, Steve, Vineis, Paolo, Kenny, Rose Anne
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container_title The journals of gerontology. Series A, Biological sciences and medical sciences
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creator McCrory, Cathal
Fiorito, Giovanni
Hernandez, Belinda
Polidoro, Silvia
O’Halloran, Aisling M
Hever, Ann
Ni Cheallaigh, Cliona
Lu, Ake T
Horvath, Steve
Vineis, Paolo
Kenny, Rose Anne
description Abstract The aging process is characterized by the presence of high interindividual variation between individuals of the same chronical age prompting a search for biomarkers that capture this heterogeneity. Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesized to represent a measure of biological aging with a positive/negative residual signifying age acceleration (AA)/deceleration, respectively. The present study examines the associations of 4 epigenetic clocks—Horvath, Hannum, PhenoAge, GrimAge—with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). HorvathAA and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of walking speed, .polypharmacy, frailty, and mortality in fully adjusted models. Results indicate that the GrimAge clock represents a step-improvement in the predictive utility of the epigenetic clocks for identifying age-related decline in an array of clinical phenotypes promising to advance precision medicine.
doi_str_mv 10.1093/gerona/glaa286
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Epigenetic clocks measure changes in DNA methylation levels at specific CpG sites that are highly correlated with calendar age. The discrepancy resulting from the regression of DNA methylation age on calendar age is hypothesized to represent a measure of biological aging with a positive/negative residual signifying age acceleration (AA)/deceleration, respectively. The present study examines the associations of 4 epigenetic clocks—Horvath, Hannum, PhenoAge, GrimAge—with a wide range of clinical phenotypes (walking speed, grip strength, Fried frailty, polypharmacy, Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MOCA), Sustained Attention Reaction Time, 2-choice reaction time), and with all-cause mortality at up to 10-year follow-up, in a sample of 490 participants in the Irish Longitudinal Study on Ageing (TILDA). HorvathAA and HannumAA were not predictive of health; PhenoAgeAA was associated with 4/9 outcomes (walking speed, frailty MOCA, MMSE) in minimally adjusted models, but not when adjusted for other social and lifestyle factors. GrimAgeAA by contrast was associated with 8/9 outcomes (all except grip strength) in minimally adjusted models, and remained a significant predictor of walking speed, .polypharmacy, frailty, and mortality in fully adjusted models. 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source MEDLINE; Oxford University Press Journals All Titles (1996-Current); Alma/SFX Local Collection
subjects Aging
Aging - genetics
Cognitive ability
CpG islands
Deoxyribonucleic acid
DNA
DNA Methylation
Editor's Choice
Epigenesis, Genetic
Epigenetics
Female
Frailty
Genetic Markers
Hand Strength
Humans
Longitudinal Studies
Male
Middle Aged
Mortality
Neuropsychological Tests
Older people
Phenotype
Phenotypes
Polypharmacy
Precision medicine
Studies
THE JOURNAL OF GERONTOLOGY: Biological Sciences
Walking Speed
title GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality
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