ArticleNature aging2022
A computational solution for bolstering reliability of epigenetic clocks: Implications for clinical trials and longitudinal tracking.
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Article in Nature aging, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 355 papers, 5 of them syntheses that pooled it.
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355citing papers in PubMed, 5 pooled it
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Who cites it
355 citing papers in PubMed, 5 syntheses or guidelines pooled it.
- Post-traumatic stress disorder moderates the association between BrainAge acceleration and GrimAge acceleration.Neurobiology of aging · 2026Pooled it
- Social determinants of health and epigenetic clocks: a systematic review and meta-analysis of 140 studies.Nature human behaviour · 2026Pooled it
- Paediatric DNA methylation profile scores: a systematic review and open-source atlas.EBioMedicine · 2026Pooled it
- The aging epigenome: integrative analyses reveal intersection with Alzheimer's disease.GeroScience · 2026Pooled it
- Methylation profile of individuals with sickle cell trait.Epigenetics · 2025Pooled it
- Blood Metabolomic Signatures of 1-Hour Glucose Predict Cardiometabolic Risk.Circulation research · 2026Trial
- Effects of a randomized controlled trial of unconditional cash transfers on epigenetic measures of ageing and cognition in children and mothers.Nature human behaviour · 2026Trial
- Semaglutide slows epigenetic aging in a randomized trial of HIV-associated lipohypertrophy.Nature communications · 2026Trial
- S-adenosylmethionine as an epigenetic treatment of depression in adults with childhood trauma.Epigenomics · 2026Trial
- Effects of daily multivitamin-multimineral and cocoa extract supplementation on epigenetic aging clocks in the COSMOS randomized clinical trial.Nature medicine · 2026Trial
- Epigenetic Age Acceleration and Cardiometabolic Biomarkers in Response to Weight-Loss Dietary Interventions Among Obese Individuals: The MACRO Trial.Aging cell · 2025Trial
- Epigenetic aging and DNA methylation biomarker changes following ketamine treatment in patients with MDD and PTSD: a pilot study.Translational psychiatry · 2025Trial
- Human clinical trial of plasmapheresis effects on biomarkers of aging (efficacy and safety trial).Scientific reports · 2025Trial
- Differential DNA methylation clock ages across buffy coat (BC), peripheral blood mononuclear cells (PBMC), and saliva in individuals in early-to-mid adulthood.Epigenetics · 2026Article
- Association between helping behaviors and epigenetic aging: Findings from the United States and Northern Ireland.SSM - population health · 2026Article
- Hypertension-associated DNA methylation signatures and multi-generational epigenetic clocks in Korean adults.GeroScience · 2026Article
- DNA methylation-based surrogate markers of C-reactive protein and their associations with health-related traits.GeroScience · 2026Article
- Epigenetic age deceleration reflects exercise-induced cardiorespiratory fitness improvements.GeroScience · 2026Article
- Epigenetic insights of Olympic champions: nuclear and mitochondrial DNA methylation and regulators of aging.GeroScience · 2026Article
- Exploring epigenetic aging and cognitive change in middle adulthood.The journals of gerontology. Series A, Biological sciences and medical sciences · 2026Article
295 more citing papers are in PubMed but not listed here.
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Authors and funding
27 authors.
Albert T Higgins-ChenDepartment of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
Kyra L ThrushProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
Yunzhang WangDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Christopher J MinteerDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Pei-Lun KuoLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Meng WangProgram in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.
Peter NiimiDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Gabriel SturmDepartments of Psychiatry and Neurology, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, United States.
Jue LinDepartment of Biochemistry and Biophysics, University of California, San Francisco, CA, United States.
Ann Zenobia MooreLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Stefania BandinelliGeriatric Unit, Azienda Sanitaria Toscana Centro, Florence, Italy.
Christiaan H VinkersDepartment of Psychiatry, Amsterdam University Medical Center, Amsterdam, The Netherlands.
Eric VermettenDepartment Psychiatry, Leiden University Medical Center, Leiden, The Netherlands.
Bart P F RuttenSchool for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Centre, Maastricht, The Netherlands.
Elbert GeuzeDepartment of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht University, The Netherlands.
Cynthia Okhuijsen-PfeiferDepartment of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht University, The Netherlands.
Marte Z van der HorstDepartment of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht University, The Netherlands.
Stefanie SchreiterDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Stefan GutwinskiDepartment of Psychiatry and Psychotherapy, Charité - Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.
Jurjen J LuykxDepartment of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht University, The Netherlands.
Martin PicardDepartments of Psychiatry and Neurology, Division of Behavioral Medicine, Columbia University Irving Medical Center, New York, NY, United States.
Luigi FerrucciLongitudinal Studies Section, Translational Gerontology Branch, National Institute on Aging, Baltimore, MD, USA.
Eileen M CrimminsDavis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
Marco P BoksDepartment of Psychiatry, Brain Center University Medical Center Utrecht, Utrecht University, The Netherlands.
Sara HäggDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Tina T Hu-SeligerElysium Health, Inc, New York, NY, USA.
Morgan E LevineDepartment of Pathology, Yale University School of Medicine, New Haven, CT, USA.
Funding
HRS Yrs29-34: Y33 SSA CoFundingU01AG009740 · NIA · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI Jessica Faul, KENNETH M LANGA · 1990 to 2026
$555.8MYale Alzheimer Disease Research CenterP30AG066508 · NIA · YALE UNIVERSITY · PI STEPHEN M STRITTMATTER · 2020 to 2026
$30.2MUSC/UCLA Center on Biodemography &Population HealthP30AG017265 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI JENNIFER A AILSHIRE · 1999 to 2026
$17.9MClinical Neuroscience Research Training Program in PsychiatryT32MH019961 · NIMH · YALE UNIVERSITY · PI Christopher John Pittenger · 1996 to 2026
$5.9MMolecular Networks Underlying Resilience to Alzheimer's Disease Among APOE E4 CarriersR01AG057912 · NIA · YALE UNIVERSITY · PI GAITERI, CHRISTOPHER A., HIGGINS-CHEN, ALBERT TZONGYANG · 2017 to 2021
$4.5MQUANTITATIVE ASSESSMENT OF BIOLOGICAL AGE AND ITS APPLICATIONSR01AG065403 · NIA · YALE UNIVERSITY · PI Vadim N. Gladyshev, Albert Tzongyang Higgins-Chen · 2020 to 2026
$4.2MMetabolic regulation of human DNA methylation clocksR01AG066828 · NIA · NEW YORK STATE PSYCHIATRIC INSTITUTE DBA RESEARCH FOUNDATION FOR MENTAL HYGIENE, INC · PI PICARD, MARTIN · 2020 to 2024
$3.2MSocial Circumstances and Epigenomics Promoting Health in Three CountriesR01AG068937 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRIMMINS, EILEEN M, FAUL, JESSICA · 2020 to 2025
$2.9MGENETIC &ENVIRONMENTAL INFLUENCES--BIOBEHAVIORAL AGINGR01AG010175 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI PEDERSEN, NANCY L · 1992 to 2006
$2.8MTuscany Regional Health Agency--Chianti Follow-up StudyN01AG50002 · NIA · REGIONAL HEALTH AGENCY OF TUSCANY · PI TRAMONTI, LAURA · 2007 to 2011
$2.7MBiological Underpinnings of Socioeconomic Differentials in Health and MortalityR01AG060110 · NIA · UNIVERSITY OF SOUTHERN CALIFORNIA · PI CRIMMINS, EILEEN M · 2018 to 2022
$2.6MAMYLOIDOGENIC INDUCTION OF CELLULAR SENESCENCE IN ALZHEIMER'S DISEASER01AG068285 · NIA · YALE UNIVERSITY · PI MIRANKER, ANDREW D. · 2020 to 2024
$2.1MNIA NIH HHS P30 AG017265NIA NIH HHS P30 AG066508NIA NIH HHS R01 AG010175NIA NIH HHS R01 AG028555NIA NIH HHS R01 AG057912NIA NIH HHS R01 AG060110NIA NIH HHS R01 AG065403NIA NIH HHS R01 AG066828NIA NIH HHS R01 AG068285NIA NIH HHS R01 AG068937NIA NIH HHS U01 AG009740NIDA NIH HHS N01AG50002NIMHD NIH HHS R01 MD009164NIMH NIH HHS T32 MH019961
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
Indexed as
DNA MethylationEpigenesis, GeneticEpigenomicsReproducibility of Resultsagingbiomarkerepigenetic clocklongitudinal analysisreliability
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