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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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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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.</description><identifier>ISSN: 1079-5006</identifier><identifier>EISSN: 1758-535X</identifier><identifier>DOI: 10.1093/gerona/glaa286</identifier><identifier>PMID: 33211845</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>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</subject><ispartof>The journals of gerontology. Series A, Biological sciences and medical sciences, 2021-05, Vol.76 (5), p.741-749</ispartof><rights>The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com. 2020</rights><rights>The Author(s) 2020. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.</rights><rights>Copyright Oxford University Press May 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c518t-7e404f70795326cbebec86fea06ebcc110d912cf7d22932b512733a5661dd5a3</citedby><cites>FETCH-LOGICAL-c518t-7e404f70795326cbebec86fea06ebcc110d912cf7d22932b512733a5661dd5a3</cites><orcidid>0000-0002-7651-5452 ; 0000-0001-8935-4566 ; 0000-0001-6575-2367</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,1583,27923,27924</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33211845$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Le Couteur, David</contributor><creatorcontrib>McCrory, Cathal</creatorcontrib><creatorcontrib>Fiorito, Giovanni</creatorcontrib><creatorcontrib>Hernandez, Belinda</creatorcontrib><creatorcontrib>Polidoro, Silvia</creatorcontrib><creatorcontrib>O’Halloran, Aisling M</creatorcontrib><creatorcontrib>Hever, Ann</creatorcontrib><creatorcontrib>Ni Cheallaigh, Cliona</creatorcontrib><creatorcontrib>Lu, Ake T</creatorcontrib><creatorcontrib>Horvath, Steve</creatorcontrib><creatorcontrib>Vineis, Paolo</creatorcontrib><creatorcontrib>Kenny, Rose Anne</creatorcontrib><title>GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality</title><title>The journals of gerontology. Series A, Biological sciences and medical sciences</title><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><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.</description><subject>Aging</subject><subject>Aging - genetics</subject><subject>Cognitive ability</subject><subject>CpG islands</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Methylation</subject><subject>Editor's Choice</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetics</subject><subject>Female</subject><subject>Frailty</subject><subject>Genetic Markers</subject><subject>Hand Strength</subject><subject>Humans</subject><subject>Longitudinal Studies</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Mortality</subject><subject>Neuropsychological Tests</subject><subject>Older people</subject><subject>Phenotype</subject><subject>Phenotypes</subject><subject>Polypharmacy</subject><subject>Precision medicine</subject><subject>Studies</subject><subject>THE JOURNAL OF GERONTOLOGY: Biological Sciences</subject><subject>Walking Speed</subject><issn>1079-5006</issn><issn>1758-535X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkUtr3DAURk1paB7ttssi6CZZONHDku1NYRjSJJAyoWTRnZDla49SjeRKcun8-2qYaWi7iTYS3HMP-viK4j3BlwS37GqE4J26Gq1StBGvihNS86bkjH97nd-4bkuOsTguTmN8wrvD6ZvimDFKSFPxk-LXTTCbxQhoNacJwuDDJqJVWkNA15MZwUEyGi2t198jMg7lCXoI0BudjHfIDygvl1_BqgR95owzWln0sAbn03aCiJTr0cLacqnmCOiLD0lZk7Zvi6NB2QjvDvdZ8fj5-nF5W96vbu6Wi_tSc9KksoYKV0Odg3BGhe6gA92IARQW0GlNCO5bQvVQ95S2jHac0JoxxYUgfc8VOys-7bXT3G2g1-BSUFZOObUKW-mVkf9OnFnL0f-UDW5qKkQWnB8Ewf-YISa5MVGDtcqBn6OklWAEk7alGf34H_rk5-ByOkk5I6xiNd4JL_eUDj7GAMPzZwiWu07lvlN56DQvfPg7wjP-p8QMXOwBP08vyX4Dhw-vPQ</recordid><startdate>20210501</startdate><enddate>20210501</enddate><creator>McCrory, Cathal</creator><creator>Fiorito, Giovanni</creator><creator>Hernandez, Belinda</creator><creator>Polidoro, Silvia</creator><creator>O’Halloran, Aisling M</creator><creator>Hever, Ann</creator><creator>Ni Cheallaigh, Cliona</creator><creator>Lu, Ake T</creator><creator>Horvath, Steve</creator><creator>Vineis, Paolo</creator><creator>Kenny, Rose Anne</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7651-5452</orcidid><orcidid>https://orcid.org/0000-0001-8935-4566</orcidid><orcidid>https://orcid.org/0000-0001-6575-2367</orcidid></search><sort><creationdate>20210501</creationdate><title>GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality</title><author>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</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c518t-7e404f70795326cbebec86fea06ebcc110d912cf7d22932b512733a5661dd5a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Aging</topic><topic>Aging - genetics</topic><topic>Cognitive ability</topic><topic>CpG islands</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Methylation</topic><topic>Editor's Choice</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Frailty</topic><topic>Genetic Markers</topic><topic>Hand Strength</topic><topic>Humans</topic><topic>Longitudinal Studies</topic><topic>Male</topic><topic>Middle Aged</topic><topic>Mortality</topic><topic>Neuropsychological Tests</topic><topic>Older people</topic><topic>Phenotype</topic><topic>Phenotypes</topic><topic>Polypharmacy</topic><topic>Precision medicine</topic><topic>Studies</topic><topic>THE JOURNAL OF GERONTOLOGY: Biological Sciences</topic><topic>Walking Speed</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>McCrory, Cathal</creatorcontrib><creatorcontrib>Fiorito, Giovanni</creatorcontrib><creatorcontrib>Hernandez, Belinda</creatorcontrib><creatorcontrib>Polidoro, Silvia</creatorcontrib><creatorcontrib>O’Halloran, Aisling M</creatorcontrib><creatorcontrib>Hever, Ann</creatorcontrib><creatorcontrib>Ni Cheallaigh, Cliona</creatorcontrib><creatorcontrib>Lu, Ake T</creatorcontrib><creatorcontrib>Horvath, Steve</creatorcontrib><creatorcontrib>Vineis, Paolo</creatorcontrib><creatorcontrib>Kenny, Rose Anne</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>The journals of gerontology. Series A, Biological sciences and medical sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCrory, Cathal</au><au>Fiorito, Giovanni</au><au>Hernandez, Belinda</au><au>Polidoro, Silvia</au><au>O’Halloran, Aisling M</au><au>Hever, Ann</au><au>Ni Cheallaigh, Cliona</au><au>Lu, Ake T</au><au>Horvath, Steve</au><au>Vineis, Paolo</au><au>Kenny, Rose Anne</au><au>Le Couteur, David</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>GrimAge Outperforms Other Epigenetic Clocks in the Prediction of Age-Related Clinical Phenotypes and All-Cause Mortality</atitle><jtitle>The journals of gerontology. Series A, Biological sciences and medical sciences</jtitle><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><date>2021-05-01</date><risdate>2021</risdate><volume>76</volume><issue>5</issue><spage>741</spage><epage>749</epage><pages>741-749</pages><issn>1079-5006</issn><eissn>1758-535X</eissn><abstract>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.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>33211845</pmid><doi>10.1093/gerona/glaa286</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-7651-5452</orcidid><orcidid>https://orcid.org/0000-0001-8935-4566</orcidid><orcidid>https://orcid.org/0000-0001-6575-2367</orcidid><oa>free_for_read</oa></addata></record> |
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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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