Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period
Abstract Background Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality. Methods We studied 63- to 76-year-...
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Veröffentlicht in: | The journals of gerontology. Series A, Biological sciences and medical sciences Biological sciences and medical sciences, 2023-08, Vol.78 (8), p.1489-1496 |
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creator | Föhr, Tiina Waller, Katja Viljanen, Anne Rantanen, Taina Kaprio, Jaakko Ollikainen, Miina Sillanpää, Elina |
description | Abstract
Background
Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality.
Methods
We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality.
Results
During the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive.
Conclusions
The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality. |
doi_str_mv | 10.1093/gerona/glad026 |
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Background
Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality.
Methods
We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality.
Results
During the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive.
Conclusions
The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality.</description><identifier>ISSN: 1079-5006</identifier><identifier>EISSN: 1758-535X</identifier><identifier>DOI: 10.1093/gerona/glad026</identifier><identifier>PMID: 36682031</identifier><language>eng</language><publisher>US: Oxford University Press</publisher><subject>Aging ; Biomarkers ; Body mass index ; Chronic illnesses ; DNA methylation ; Epigenetics ; Mortality ; Physical activity ; Regression analysis ; THE JOURNAL OF GERONTOLOGY: Medical Sciences</subject><ispartof>The journals of gerontology. Series A, Biological sciences and medical sciences, 2023-08, Vol.78 (8), p.1489-1496</ispartof><rights>The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America. 2023</rights><rights>The Author(s) 2023. Published by Oxford University Press on behalf of The Gerontological Society of America.</rights><rights>Copyright Oxford University Press Aug 2023</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c453t-2aace84e01032edcfc3a8dd137b584b23e4dd0a121aae2d03b7d43d53c705f3f3</citedby><cites>FETCH-LOGICAL-c453t-2aace84e01032edcfc3a8dd137b584b23e4dd0a121aae2d03b7d43d53c705f3f3</cites><orcidid>0000-0002-1654-1333 ; 0000-0002-0121-249X ; 0000-0001-6375-959X ; 0000-0002-1604-1945</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,782,786,887,1586,27931,27932</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36682031$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Lipsitz, Lewis</contributor><creatorcontrib>Föhr, Tiina</creatorcontrib><creatorcontrib>Waller, Katja</creatorcontrib><creatorcontrib>Viljanen, Anne</creatorcontrib><creatorcontrib>Rantanen, Taina</creatorcontrib><creatorcontrib>Kaprio, Jaakko</creatorcontrib><creatorcontrib>Ollikainen, Miina</creatorcontrib><creatorcontrib>Sillanpää, Elina</creatorcontrib><title>Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period</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
Background
Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality.
Methods
We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality.
Results
During the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive.
Conclusions
The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality.</description><subject>Aging</subject><subject>Biomarkers</subject><subject>Body mass index</subject><subject>Chronic illnesses</subject><subject>DNA methylation</subject><subject>Epigenetics</subject><subject>Mortality</subject><subject>Physical activity</subject><subject>Regression analysis</subject><subject>THE JOURNAL OF GERONTOLOGY: Medical Sciences</subject><issn>1079-5006</issn><issn>1758-535X</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>TOX</sourceid><recordid>eNqFkU1v1DAQhi1ERUvhyhFZ4gKHtP6Ik-wJpYVtkbrQAwg4WbO2k3Xltbd20mr_AL-73g8q4IIvY80889ozL0KvKDmhZMJPexODh9PegSaseoKOaC2aQnDx42m-k3pSCEKqQ_Q8pRuyOYI9Q4e8qhpGOD1Cv2YhDuDssMZtSkFZGGzwCX-3wwJ_-NzimRkWa7fNFmeQjMZnNrjQWwUOt731PQav8fVinbap6ejVBt4UZgbSGE3CrYohJQyYkeKngYinwblwX4wrfG2iDfoFOujAJfNyH4_Rt-nHr-eXxdWXi0_n7VWhSsGHggEo05SGUMKZ0apTHBqtKa_noinnjJtSawKUUQDDNOHzWpdcC65qIjre8WP0fqe7GufLLGD8EMHJVbRLiGsZwMq_K94uZB_uZH5wIoSYZIW3e4UYbkeTBrm0SRnnwJswJsnqvFpOSUUz-uYf9CaM0ef5JGvKmtQVFyJTJztqu6NousffUCI3Hsudx3LvcW54_ecMj_hvUzPwbgeEcfU_sQcVPbUv</recordid><startdate>20230802</startdate><enddate>20230802</enddate><creator>Föhr, Tiina</creator><creator>Waller, Katja</creator><creator>Viljanen, Anne</creator><creator>Rantanen, Taina</creator><creator>Kaprio, Jaakko</creator><creator>Ollikainen, Miina</creator><creator>Sillanpää, Elina</creator><general>Oxford University Press</general><scope>TOX</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/0000-0002-1654-1333</orcidid><orcidid>https://orcid.org/0000-0002-0121-249X</orcidid><orcidid>https://orcid.org/0000-0001-6375-959X</orcidid><orcidid>https://orcid.org/0000-0002-1604-1945</orcidid></search><sort><creationdate>20230802</creationdate><title>Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period</title><author>Föhr, Tiina ; Waller, Katja ; Viljanen, Anne ; Rantanen, Taina ; Kaprio, Jaakko ; Ollikainen, Miina ; Sillanpää, Elina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c453t-2aace84e01032edcfc3a8dd137b584b23e4dd0a121aae2d03b7d43d53c705f3f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>Aging</topic><topic>Biomarkers</topic><topic>Body mass index</topic><topic>Chronic illnesses</topic><topic>DNA methylation</topic><topic>Epigenetics</topic><topic>Mortality</topic><topic>Physical activity</topic><topic>Regression analysis</topic><topic>THE JOURNAL OF GERONTOLOGY: Medical Sciences</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Föhr, Tiina</creatorcontrib><creatorcontrib>Waller, Katja</creatorcontrib><creatorcontrib>Viljanen, Anne</creatorcontrib><creatorcontrib>Rantanen, Taina</creatorcontrib><creatorcontrib>Kaprio, Jaakko</creatorcontrib><creatorcontrib>Ollikainen, Miina</creatorcontrib><creatorcontrib>Sillanpää, Elina</creatorcontrib><collection>Access via Oxford University Press (Open Access Collection)</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>Föhr, Tiina</au><au>Waller, Katja</au><au>Viljanen, Anne</au><au>Rantanen, Taina</au><au>Kaprio, Jaakko</au><au>Ollikainen, Miina</au><au>Sillanpää, Elina</au><au>Lipsitz, Lewis</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period</atitle><jtitle>The journals of gerontology. Series A, Biological sciences and medical sciences</jtitle><addtitle>J Gerontol A Biol Sci Med Sci</addtitle><date>2023-08-02</date><risdate>2023</risdate><volume>78</volume><issue>8</issue><spage>1489</spage><epage>1496</epage><pages>1489-1496</pages><issn>1079-5006</issn><eissn>1758-535X</eissn><abstract>Abstract
Background
Measures of biological aging range from DNA methylation (DNAm)-based estimates to measures of physical abilities. The purpose of this study was to compare DNAm- and physical functioning-based measures of biological aging in predicting mortality.
Methods
We studied 63- to 76-year-old women (N = 395) from the Finnish Twin Study on Aging (FITSA). Participants’ biological age (epigenetic clocks DNAm GrimAge and DunedinPACE) was estimated using blood DNAm data. Tests of physical functioning conducted under standardized laboratory conditions included the Timed Up and Go (TUG) test and 10-m walk test. Mortality hazard ratios were calculated per every 1 standard deviation (SD) increase in the predictor. Cox regression models were conducted for individuals and twin pairs, the latter controlling for underlying genetic effects. The models were adjusted for known lifestyle predictors of mortality.
Results
During the follow-up period (mean 17.0 years, range 0.2–20.3), 187 participants died. In both the individual-based and pairwise analyses, GrimAge and both functional biomarkers of aging were associated with mortality independent of family relatedness, chronological age, physical activity, body mass index, smoking, education, or chronic diseases. In a model including both the DNAm-based measures and functional biomarkers of aging, GrimAge and TUG remained predictive.
Conclusions
The findings suggest that DNAm GrimAge and the TUG test are strong predictors of mortality independent of each others and genetic influences. DNAm-based measures and functional tests capture different aspects of the aging process and thus complement each other as measures of biological aging in predicting mortality.</abstract><cop>US</cop><pub>Oxford University Press</pub><pmid>36682031</pmid><doi>10.1093/gerona/glad026</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0002-1654-1333</orcidid><orcidid>https://orcid.org/0000-0002-0121-249X</orcidid><orcidid>https://orcid.org/0000-0001-6375-959X</orcidid><orcidid>https://orcid.org/0000-0002-1604-1945</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Aging Biomarkers Body mass index Chronic illnesses DNA methylation Epigenetics Mortality Physical activity Regression analysis THE JOURNAL OF GERONTOLOGY: Medical Sciences |
title | Mortality Associations With DNA Methylation-Based Biological Aging and Physical Functioning Measures Across a 20-Year Follow-up Period |
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