Accelerated Epigenetic Aging Is Associated With Multiple Cardiometabolic, Hematologic, and Renal Abnormalities: A Project Baseline Health Substudy.
aging
body mass index
deceleration
lipids
methylation
Journal
Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113
Informations de publication
Date de publication:
06 2023
06 2023
Historique:
pmc-release:
01
06
2024
medline:
22
6
2023
pubmed:
12
4
2023
entrez:
11
4
2023
Statut:
ppublish
Résumé
Epigenetic clocks estimate chronologic age using methylation levels at specific loci. We tested the hypothesis that accelerated epigenetic aging is associated with abnormal values in a range of clinical, imaging, and laboratory characteristics. The Project Baseline Health Study recruited 2502 participants, including 1661 with epigenetic age estimates from the Horvath pan-tissue clock. We classified individuals with extreme values as having epigenetic age acceleration (EAA) or epigenetic age deceleration. A subset of participants with longitudinal methylation profiling was categorized as accelerated versus nonaccelerated. Using principal components analysis, we created phenoclusters using 122 phenotypic variables and compared individuals with EAA versus epigenetic age deceleration, and at one year of follow-up, using logistic regression models adjusted for sex (false discovery rate [ The EAA (n=188) and epigenetic age deceleration (n=195) groups were identified as having EAA estimates ≥5 years or ≤-5 years, respectively. In primary analyses, individuals with EAA had higher values for phenoclusters summarizing lung function and lipids, and lower values for a phenocluster representing physical function. In secondary analyses of individual variables, neutrophils, body mass index, and waist circumference were significantly higher in individuals with EAA ( We report multiple cardiometabolic, hematologic, and physical function features characterizing individuals with EAA. These highlight factors that may mediate the adverse effects of aging and identify potential targets for study of mitigation of these effects. URL: https://www. gov; Unique identifier: NCT03154346.
Sections du résumé
BACKGROUND
Epigenetic clocks estimate chronologic age using methylation levels at specific loci. We tested the hypothesis that accelerated epigenetic aging is associated with abnormal values in a range of clinical, imaging, and laboratory characteristics.
METHODS
The Project Baseline Health Study recruited 2502 participants, including 1661 with epigenetic age estimates from the Horvath pan-tissue clock. We classified individuals with extreme values as having epigenetic age acceleration (EAA) or epigenetic age deceleration. A subset of participants with longitudinal methylation profiling was categorized as accelerated versus nonaccelerated. Using principal components analysis, we created phenoclusters using 122 phenotypic variables and compared individuals with EAA versus epigenetic age deceleration, and at one year of follow-up, using logistic regression models adjusted for sex (false discovery rate [
RESULTS
The EAA (n=188) and epigenetic age deceleration (n=195) groups were identified as having EAA estimates ≥5 years or ≤-5 years, respectively. In primary analyses, individuals with EAA had higher values for phenoclusters summarizing lung function and lipids, and lower values for a phenocluster representing physical function. In secondary analyses of individual variables, neutrophils, body mass index, and waist circumference were significantly higher in individuals with EAA (
CONCLUSIONS
We report multiple cardiometabolic, hematologic, and physical function features characterizing individuals with EAA. These highlight factors that may mediate the adverse effects of aging and identify potential targets for study of mitigation of these effects.
REGISTRATION
URL: https://www.
CLINICALTRIALS
gov; Unique identifier: NCT03154346.
Identifiants
pubmed: 37039013
doi: 10.1161/CIRCGEN.122.003772
pmc: PMC10330131
mid: NIHMS1887724
doi:
Banques de données
ClinicalTrials.gov
['NCT03154346']
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
216-223Subventions
Organisme : NHLBI NIH HHS
ID : R01 HL146145
Pays : United States
Références
Aging Cell. 2012 Dec;11(6):1132-4
pubmed: 23061750
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15538-43
pubmed: 25313081
Aging (Albany NY). 2015 Sep;7(9):690-700
pubmed: 26411804
Clin Epigenetics. 2016 Jun 03;8:64
pubmed: 27274774
Clin Epigenetics. 2021 Jun 2;13(1):121
pubmed: 34078457
Science. 1975 Jan 24;187(4173):226-32
pubmed: 1111098
Genome Biol. 2014 Feb 03;15(2):R24
pubmed: 24490752
Curr Opin Ophthalmol. 2014 Mar;25(2):104-11
pubmed: 24370973
Aging (Albany NY). 2017 Feb 14;9(2):419-446
pubmed: 28198702
Clin Epigenetics. 2021 Jan 7;13(1):7
pubmed: 33413638
Ageing Res Rev. 2003 Jul;2(3):245-61
pubmed: 12726774
PeerJ. 2020 Jun 02;8:e9279
pubmed: 32676219
Clin Epigenetics. 2017 Feb 14;9:21
pubmed: 28289478
Arch Neurol. 2009 Nov;66(11):1366-72
pubmed: 19901168
Genome Res. 2010 Apr;20(4):440-6
pubmed: 20219944
Rejuvenation Res. 2012 Oct;15(5):483-94
pubmed: 23098078
NPJ Digit Med. 2020 Jun 5;3:84
pubmed: 32550652
Clin Epigenetics. 2021 Mar 16;13(1):55
pubmed: 33726838
Nat Rev Genet. 2018 Jun;19(6):371-384
pubmed: 29643443
Aging (Albany NY). 2018 Apr 18;10(4):573-591
pubmed: 29676998
PLoS One. 2020 Jan 30;15(1):e0227728
pubmed: 31999706
Am J Kidney Dis. 2013 Aug;62(2):339-51
pubmed: 23357108
J Cell Physiol. 2019 Sep;234(9):14852-14864
pubmed: 30767204
Clin Epigenetics. 2012 Jul 02;4(1):10
pubmed: 22748066
Circ Cardiovasc Genet. 2010 Apr;3(2):207-14
pubmed: 20173117
Front Genet. 2019 Oct 29;10:1062
pubmed: 31737045
Aging (Albany NY). 2018 Nov 10;10(11):3210-3228
pubmed: 30414594
Hum Mol Genet. 2015 Jul 1;24(13):3792-813
pubmed: 25861810
Trends Genet. 2008 May;24(5):231-7
pubmed: 18325624
Genome Biol. 2016 Aug 11;17(1):171
pubmed: 27511193
Invest Ophthalmol Vis Sci. 2014 Sep 23;55(10):6802-16
pubmed: 25249610
Arq Bras Oftalmol. 2012 May-Jun;75(3):183-7
pubmed: 22872201
Oncotarget. 2016 Nov 15;7(46):74510-74525
pubmed: 27793020
Clin Epigenetics. 2018 Apr 18;10:56
pubmed: 29713391
Genome Biol. 2012 Oct 03;13(10):R97
pubmed: 23034122
Am J Epidemiol. 2018 Mar 1;187(3):529-538
pubmed: 29020168
Genome Biol. 2019 Nov 25;20(1):249
pubmed: 31767039
Bioinformatics. 2017 Feb 15;33(4):558-560
pubmed: 28035024
Int J Epidemiol. 2012 Feb;41(1):210-7
pubmed: 22422454
Nat Commun. 2017 Nov 3;8(1):1286
pubmed: 29097680
Genome Biol. 2013;14(10):R115
pubmed: 24138928