{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:33:28Z","timestamp":1790660008440,"version":"4.1.0"},"reference-count":96,"publisher":"eLife Sciences Publications, Ltd","license":[{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"am","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T00:00:00Z","timestamp":1686009600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MR\/S03532X\/1"],"award-info":[{"award-number":["MR\/S03532X\/1"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000780","name":"European Commission","doi-asserted-by":"publisher","award":["308333 874583"],"award-info":[{"award-number":["308333 874583"]}],"id":[{"id":"10.13039\/501100000780","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Secretaria d\u2019Universitats i Recerca del Departament d\u2019Economia i Coneixement de la Generalitat de Catalunya","award":["2017SGR595"],"award-info":[{"award-number":["2017SGR595"]}]},{"DOI":"10.13039\/501100010552","name":"Departament de Salut de la Generalitat de Catalunya","doi-asserted-by":"crossref","award":["SLT017\/20\/000119"],"award-info":[{"award-number":["SLT017\/20\/000119"]}],"id":[{"id":"10.13039\/501100010552","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["elifesciences.org"],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,6,6]]},"abstract":"<jats:sec id=\"abs1\">\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>While biological age in adults is often understood as representing general health and resilience, the conceptual interpretation of accelerated biological age in children and its relationship to development remains unclear. We aimed to clarify the relationship of accelerated biological age, assessed through two established biological age indicators, telomere length and DNA methylation age, and two novel candidate biological age indicators, to child developmental outcomes, including growth and adiposity, cognition, behavior, lung function and the onset of puberty, among European school-age children participating in the HELIX exposome cohort.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs2\">\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>The study population included up to 1173 children, aged between 5 and 12 years, from study centres in the UK, France, Spain, Norway, Lithuania, and Greece. Telomere length was measured through qPCR, blood DNA methylation, and gene expression was measured using microarray, and proteins and metabolites were measured by a range of targeted assays. DNA methylation age was assessed using Horvath\u2019s skin and blood clock, while novel blood transcriptome and \u2018immunometabolic\u2019 (based on plasma proteins and urinary and serum metabolites) clocks were derived and tested in a subset of children assessed six months after the main follow-up visit. Associations between biological age indicators with child developmental measures as well as health risk factors were estimated using linear regression, adjusted for chronological age, sex, ethnicity, and study centre. The clock derived markers were expressed as \u0394 age (i.e. predicted minus chronological age).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs3\">\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      Transcriptome and immunometabolic clocks predicted chronological age well in the test set (\n                      <jats:italic>r<\/jats:italic>\n                      =0.93 and\n                      <jats:italic>r<\/jats:italic>\n                      =0.84 respectively). Generally, weak correlations were observed, after adjustment for chronological age, between the biological age indicators.\n                    <\/jats:p>\n                    <jats:p>Among associations with health risk factors, higher birthweight was associated with greater immunometabolic \u0394 age, smoke exposure with greater DNA methylation \u0394 age, and high family affluence with longer telomere length.<\/jats:p>\n                    <jats:p>Among associations with child developmental measures, all biological age markers were associated with greater BMI and fat mass, and all markers except telomere length were associated with greater height, at least at nominal significance (p&lt;0.05). Immunometabolic \u0394 age was associated with better working memory (p=4 e\u20133) and reduced inattentiveness (p=4 e\u20134), while DNA methylation \u0394 age was associated with greater inattentiveness (p=0.03) and poorer externalizing behaviors (p=0.01). Shorter telomere length was also associated with poorer externalizing behaviors (p=0.03).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs4\">\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>In children, as in adults, biological aging appears to be a multi-faceted process and adiposity is an important correlate of accelerated biological aging. Patterns of associations suggested that accelerated immunometabolic age may be beneficial for some aspects of child development while accelerated DNA methylation age and telomere attrition may reflect early detrimental aspects of biological aging, apparent even in children.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"abs5\">\n                    <jats:title>Funding:<\/jats:title>\n                    <jats:p>UK Research and Innovation (MR\/S03532X\/1); European Commission (grant agreement numbers: 308333; 874583).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.7554\/elife.85104","type":"journal-article","created":{"date-parts":[[2023,6,6]],"date-time":"2023-06-06T15:09:40Z","timestamp":1686064180000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.85104","source":"Crossref","is-referenced-by-count":19,"title":["Associations of four biological age markers with child development: A multi-omic analysis in the European HELIX cohort"],"prefix":"10.7554","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4735-0468","authenticated-orcid":true,"given":"Oliver","family":"Robinson","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041kmwe10","id-type":"ROR","asserted-by":"publisher"}],"name":"\u039cedical Research Council Centre for Environment and Health, Imperial College London","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/041kmwe10","id-type":"ROR","asserted-by":"publisher"}],"name":"Mohn Centre for Children's Health and Well-being, School of Public Health, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"ChungHo E","family":"Lau","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041kmwe10","id-type":"ROR","asserted-by":"publisher"}],"name":"\u039cedical Research Council Centre for Environment and Health, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sungyeon","family":"Joo","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041kmwe10","id-type":"ROR","asserted-by":"publisher"}],"name":"\u039cedical Research Council Centre for Environment and Health, Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Andrusaityte","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04y7eh037","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Environmental Science, Vytautas Magnus University","place":["Kaunas, Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva","family":"Borras","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kpps236","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Genomics Regulation, Barcelona Institute of Science and Technology","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/04n0g0b29","id-type":"ROR","asserted-by":"publisher"}],"name":"Universitat Pompeu Fabra (UPF)","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"de Prado-Bert","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04n0g0b29","id-type":"ROR","asserted-by":"publisher"}],"name":"Universitat Pompeu Fabra (UPF)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/03hjgt059","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Global Health (ISGlobal)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"publisher"}],"name":"CIBER Epidemiologa y Salud P\u00fablica (CIBERESP)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lida","family":"Chatzi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03taz7m60","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Preventive Medicine, Keck School of Medicine, University of Southern California","place":["Los Angeles, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hector C","family":"Keun","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/041kmwe10","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Systems Medicine, Department of Metabolism, Digestion and Reproduction, Imperial College London","place":["London, United Kingdom"]},{"id":[{"id":"https:\/\/ror.org\/041kmwe10","id-type":"ROR","asserted-by":"publisher"}],"name":"Cancer Metabolism & Systems Toxicology Group, Division of Cancer, Department of Surgery & Cancer; Imperial College London","place":["London, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Regina","family":"Grazuleviciene","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04y7eh037","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Environmental Science, Vytautas Magnus University","place":["Kaunas, Lithuania"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6716-5921","authenticated-orcid":true,"given":"Kristine B","family":"Gutzkow","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/046nvst19","id-type":"ROR","asserted-by":"publisher"}],"name":"Division of Climate and Environmental Health, Norwegian Institute of Public Health","place":["Oslo, Norway"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lea","family":"Maitre","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04n0g0b29","id-type":"ROR","asserted-by":"publisher"}],"name":"Universitat Pompeu Fabra (UPF)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/03hjgt059","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Global Health (ISGlobal)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"publisher"}],"name":"CIBER Epidemiologa y Salud P\u00fablica (CIBERESP)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dries S","family":"Martens","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04nbhqj75","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Environmental Sciences, Hasselt University","place":["Hasselt, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6506-7714","authenticated-orcid":true,"given":"Eduard","family":"Sabido","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/03kpps236","id-type":"ROR","asserted-by":"publisher"}],"name":"Center for Genomics Regulation, Barcelona Institute of Science and Technology","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/04n0g0b29","id-type":"ROR","asserted-by":"publisher"}],"name":"Universitat Pompeu Fabra (UPF)","place":["Barcelona, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Siroux","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02rx3b187","id-type":"ROR","asserted-by":"publisher"}],"name":"University Grenoble Alpes, Inserm U 1209, CNRS UMR 5309, Team of environmental epidemiology applied to the development and respiratory health, Institute for Advanced Biosciences","place":["38000 Grenoble, France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Urquiza","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04n0g0b29","id-type":"ROR","asserted-by":"publisher"}],"name":"Universitat Pompeu Fabra (UPF)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/03hjgt059","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Global Health (ISGlobal)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"publisher"}],"name":"CIBER Epidemiologa y Salud P\u00fablica (CIBERESP)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Vafeiadi","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00dr28g20","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Social Medicine, School of Medicine, University of Crete, Heraklion","place":["Crete, Greece"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John","family":"Wright","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/05gekvn04","id-type":"ROR","asserted-by":"publisher"}],"name":"Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust","place":["Bradford, United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim S","family":"Nawrot","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04nbhqj75","id-type":"ROR","asserted-by":"publisher"}],"name":"Centre for Environmental Sciences, Hasselt University","place":["Hasselt, Belgium"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariona","family":"Bustamante","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04n0g0b29","id-type":"ROR","asserted-by":"publisher"}],"name":"Universitat Pompeu Fabra (UPF)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/03hjgt059","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Global Health (ISGlobal)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"publisher"}],"name":"CIBER Epidemiologa y Salud P\u00fablica (CIBERESP)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Vrijheid","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04n0g0b29","id-type":"ROR","asserted-by":"publisher"}],"name":"Universitat Pompeu Fabra (UPF)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/03hjgt059","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute for Global Health (ISGlobal)","place":["Barcelona, Spain"]},{"id":[{"id":"https:\/\/ror.org\/02g87qh62","id-type":"ROR","asserted-by":"publisher"}],"name":"CIBER Epidemiologa y Salud P\u00fablica (CIBERESP)","place":["Madrid, Spain"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4374","published-online":{"date-parts":[[2023,6,6]]},"reference":[{"key":"bib1","volume-title":"Manual for ASEBA School-Age Forms & Profiles","author":"Achenbach","year":"2001"},{"key":"bib2","doi-asserted-by":"publisher","first-page":"e81","DOI":"10.1016\/S2542-5196(19)30010-5","article-title":"Early-life exposome and lung function in children in Europe: an analysis of data from the longitudinal, population-based HELIX cohort","volume":"3","author":"Agier","year":"2019","journal-title":"The Lancet. Planetary Health"},{"key":"bib3","doi-asserted-by":"publisher","first-page":"1220","DOI":"10.1093\/aje\/kwx346","article-title":"Eleven telomere, epigenetic clock, and biomarker-composite quantifications of biological aging: Do they measure the same thing","volume":"187","author":"Belsky","year":"2018","journal-title":"American Journal of Epidemiology"},{"key":"bib4","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.54870","article-title":"Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm","volume":"9","author":"Belsky","year":"2020","journal-title":"eLife"},{"key":"bib5","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society"},{"key":"bib6","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1080\/15592294.2017.1414127","article-title":"Faster ticking rate of the epigenetic clock is associated with faster pubertal development in girls","volume":"13","author":"Binder","year":"2018","journal-title":"Epigenetics"},{"key":"bib7","first-page":"241","volume-title":"Handbook of Theory and Research for the Sociology of Education","author":"Bourdieu","year":"1986"},{"key":"bib8","doi-asserted-by":"publisher","first-page":"473","DOI":"10.1007\/s11205-005-1607-6","article-title":"The family affluence scale as a measure of national wealth: validation of an adolescent self-report measure","volume":"78","author":"Boyce","year":"2006","journal-title":"Social Indicators Research"},{"key":"bib9","doi-asserted-by":"publisher","first-page":"2084","DOI":"10.1093\/bioinformatics\/btu161","article-title":"massiR: a method for predicting the sex of samples in gene expression Microarray Datasets","volume":"30","author":"Buckberry","year":"2014","journal-title":"Bioinformatics"},{"key":"bib10","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1210\/jc.2010-2924","article-title":"Childhood obesity is associated with shorter leukocyte telomere length","volume":"96","author":"Buxton","year":"2011","journal-title":"The Journal of Clinical Endocrinology and Metabolism"},{"key":"bib11","doi-asserted-by":"publisher","first-page":"1141","DOI":"10.1016\/S1470-2045(12)70425-4","article-title":"Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies","volume":"13","author":"Cancer\"","year":"2012","journal-title":"The Lancet Oncology"},{"key":"bib12","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkn1027","article-title":"Telomere length measurement by a novel monochrome multiplex quantitative PCR method","volume":"37","author":"Cawthon","year":"2009","journal-title":"Nucleic Acids Research"},{"key":"bib13","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1093\/aje\/kwu113","article-title":"Age at menarche and risks of all-cause and cardiovascular death: a systematic review and meta-analysis","volume":"180","author":"Charalampopoulos","year":"2014","journal-title":"American Journal of Epidemiology"},{"key":"bib14","doi-asserted-by":"publisher","first-page":"1392","DOI":"10.1093\/ije\/dyx084","article-title":"Cohort profile: the mother-child cohort in Crete, Greece (Rhea study)","volume":"46","author":"Chatzi","year":"2017","journal-title":"International Journal of Epidemiology"},{"key":"bib15","doi-asserted-by":"publisher","first-page":"203","DOI":"10.4161\/epi.23470","article-title":"Discovery of cross-reactive probes and polymorphic CpGs in the Illumina Infinium HumanMethylation450 Microarray","volume":"8","author":"Chen","year":"2013","journal-title":"Epigenetics"},{"key":"bib16","doi-asserted-by":"publisher","first-page":"1844","DOI":"10.18632\/aging.101020","article-title":"DNA methylation-based measures of biological age: meta-analysis predicting time to death","volume":"8","author":"Chen","year":"2016","journal-title":"Aging"},{"key":"bib17","doi-asserted-by":"publisher","first-page":"1813","DOI":"10.1038\/oby.2011.158","article-title":"A new BIA equation estimating the body composition of young children","volume":"19","author":"Clasey","year":"2011","journal-title":"Obesity"},{"key":"bib18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jpsychires.2017.03.023","article-title":"Stress-related telomere length in children: A systematic review","volume":"92","author":"Coimbra","year":"2017","journal-title":"Journal of Psychiatric Research"},{"key":"bib19","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2015.00028","article-title":"Telomere length is highly inherited and associated with hyperactivity-Impulsivity in children with attention deficit\/hyperactivity disorder","volume":"8","author":"Costa","year":"2015","journal-title":"Frontiers in Molecular Neuroscience"},{"key":"bib20","doi-asserted-by":"publisher","first-page":"672","DOI":"10.1007\/s10578-021-01279-3","article-title":"Associations between children\u2019s telomere length, parental Intrusiveness, and the development of early externalizing behaviors","volume":"54","author":"Daoust","year":"2023","journal-title":"Child Psychiatry and Human Development"},{"key":"bib21","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1136\/jech.54.2.97","article-title":"Height and risk of death among men and women: Aetiological implications of associations with cardiorespiratory disease and cancer mortality","volume":"54","author":"Davey Smith","year":"2000","journal-title":"Journal of Epidemiology and Community Health"},{"key":"bib22","doi-asserted-by":"publisher","first-page":"660","DOI":"10.2471\/blt.07.043497","article-title":"Development of a WHO growth reference for school-aged children and adolescents","volume":"85","author":"de Onis","year":"2007","journal-title":"Bulletin of the World Health Organization"},{"key":"bib23","doi-asserted-by":"publisher","DOI":"10.1016\/j.envint.2021.106683","article-title":"The early-life exposome and epigenetic age acceleration in children","volume":"155","author":"de Prado-Bert","year":"2021","journal-title":"Environment International"},{"key":"bib24","doi-asserted-by":"publisher","first-page":"4281","DOI":"10.1021\/ac051632c","article-title":"Probabilistic quotient normalization as robust method to account for dilution of complex biological mixtures. application in 1H NMR Metabonomics","volume":"78","author":"Dieterle","year":"2006","journal-title":"Analytical Chemistry"},{"key":"bib25","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a041195","article-title":"Evolutionary approaches in aging research","volume":"12","author":"Emery Thompson","year":"2022","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"bib26","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13080","article-title":"Measuring biological aging in humans: A quest","volume":"19","author":"Ferrucci","year":"2020","journal-title":"Aging Cell"},{"key":"bib27","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.18632\/aging.101900","article-title":"Socioeconomic position, lifestyle habits and biomarkers of epigenetic aging: a multi-cohort analysis","volume":"11","author":"Fiorito","year":"2019","journal-title":"Aging"},{"key":"bib28","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1037\/neu0000085","article-title":"The N-back test and the attentional network task as measures of child neuropsychological development in Epidemiological studies","volume":"28","author":"Forns","year":"2014","journal-title":"Neuropsychology"},{"key":"bib29","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-014-0503-2","article-title":"Functional normalization of 450K methylation array data improves replication in large cancer studies","volume":"15","author":"Fortin","year":"2014","journal-title":"Genome Biology"},{"key":"bib30","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1016\/j.exger.2013.12.004","article-title":"Gender and telomere length: systematic review and meta-analysis","volume":"51","author":"Gardner","year":"2014","journal-title":"Experimental Gerontology"},{"key":"bib31","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay5969","article-title":"Metabolic maturation in the first 2 years of life in resource-constrained settings and its association with postnatal growths","volume":"6","author":"Giallourou","year":"2020","journal-title":"Science Advances"},{"key":"bib32","doi-asserted-by":"publisher","first-page":"1282","DOI":"10.3390\/ijerph6031282","article-title":"Maternal smoking, GSTM1 and GSTT1 polymorphism and susceptibility to adverse pregnancy outcomes","volume":"6","author":"Grazuleviciene","year":"2009","journal-title":"International Journal of Environmental Research and Public Health"},{"key":"bib33","doi-asserted-by":"publisher","first-page":"930","DOI":"10.1093\/ije\/dyr054","article-title":"Cohort profile: the INMA--INfancia Y Medio Ambiente--(Environment and childhood) project","volume":"41","author":"Guxens","year":"2012","journal-title":"International Journal of Epidemiology"},{"key":"bib34","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.63425","article-title":"Sex differences in biological aging with a focus on human studies","volume":"10","author":"H\u00e4gg","year":"2021","journal-title":"eLife"},{"key":"bib35","article-title":"Illuminahumanmethylation450Kmanifest: Annotation for Illumina\u2019s 450K methylation Arrays","volume-title":"Bioconductor","author":"Hansen KD","year":"2012","unstructured":"Hansen KD AM. 2012. Illuminahumanmethylation450Kmanifest: Annotation for Illumina\u2019s 450K methylation Arrays. Bioconductor. 3.17. https:\/\/bioconductor.org\/packages\/release\/data\/annotation\/html\/IlluminaHumanMethylation450kmanifest.html."},{"key":"bib36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0094385","article-title":"Shorter men live longer: Association of height with longevity and Foxo3 genotype in American men of Japanese ancestry","volume":"9","author":"He","year":"2014","journal-title":"PLOS ONE"},{"key":"bib37","doi-asserted-by":"publisher","first-page":"400","DOI":"10.1021\/acs.jproteome.5b00561","article-title":"Measuring biological age via metabonomics: the metabolic age score","volume":"15","author":"Hertel","year":"2016","journal-title":"Journal of Proteome Research"},{"key":"bib38","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1093\/ije\/dyv151","article-title":"Cohort profile: the EDEN mother-child cohort on the prenatal and early postnatal determinants of child health and development","volume":"45","author":"Heude","year":"2016","journal-title":"International Journal of Epidemiology"},{"key":"bib39","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2013-14-10-r115","article-title":"DNA methylation age of human tissues and cell types","volume":"14","author":"Horvath","year":"2013","journal-title":"Genome Biology"},{"key":"bib40","doi-asserted-by":"publisher","first-page":"1758","DOI":"10.18632\/aging.101508","article-title":"Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria syndrome and ex Vivo studies","volume":"10","author":"Horvath","year":"2018","journal-title":"Aging"},{"key":"bib41","doi-asserted-by":"publisher","first-page":"371","DOI":"10.1038\/s41576-018-0004-3","article-title":"DNA methylation-based biomarkers and the epigenetic clock theory of ageing","volume":"19","author":"Horvath","year":"2018","journal-title":"Nature Reviews. Genetics"},{"key":"bib42","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1038\/nature21363","article-title":"Inflammation, metaflammation and immunometabolic disorders","volume":"542","author":"Hotamisligil","year":"2017","journal-title":"Nature"},{"key":"bib43","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-021-02030-4","article-title":"Investigating causal relationships between exposome and human longevity: a Mendelian randomization analysis","volume":"19","author":"Huang","year":"2021","journal-title":"BMC Medicine"},{"key":"bib44","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.59479","article-title":"An integrative study of five biological clocks in somatic and mental health","volume":"10","author":"Jansen","year":"2021","journal-title":"eLife"},{"key":"bib45","doi-asserted-by":"publisher","first-page":"118","DOI":"10.1093\/biostatistics\/kxj037","article-title":"Adjusting batch effects in microarray expression data using empirical Bayes methods","volume":"8","author":"Johnson","year":"2007","journal-title":"Biostatistics"},{"key":"bib46","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2021.117404","article-title":"Early life multiple exposures and child cognitive function: A multi-centric birth cohort study in six European countries","volume":"284","author":"Julvez","year":"2021","journal-title":"Environmental Pollution"},{"key":"bib47","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/j.ebiom.2017.03.046","article-title":"Biological age predictors","volume":"21","author":"Jylh\u00e4v\u00e4","year":"2017","journal-title":"EBioMedicine"},{"key":"bib48","doi-asserted-by":"publisher","first-page":"193","DOI":"10.1016\/j.jpeds.2020.02.075","article-title":"Early puberty and telomere length in preadolescent girls and mothers","volume":"222","author":"Koss","year":"2020","journal-title":"The Journal of Pediatrics"},{"key":"bib49","doi-asserted-by":"publisher","first-page":"533","DOI":"10.1097\/PSY.0b013e318229acfc","article-title":"Autonomic and adrenocortical reactivity and buccal cell telomere length in kindergarten children","volume":"73","author":"Kroenke","year":"2011","journal-title":"Psychosomatic Medicine"},{"key":"bib50","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1093\/gerona\/62.7.717","article-title":"A life course approach to healthy aging, frailty, and capability","volume":"62","author":"Kuh","year":"2007","journal-title":"The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences"},{"key":"bib51","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-018-1190-8","article-title":"Determinants of the urinary and serum metabolome in children from six European populations","volume":"16","author":"Lau","year":"2018","journal-title":"BMC Medicine"},{"key":"bib52","doi-asserted-by":"publisher","first-page":"1843","DOI":"10.1038\/s41591-019-0673-2","article-title":"Undulating changes in human plasma proteome profiles across the lifespan","volume":"25","author":"Lehallier","year":"2019","journal-title":"Nature Medicine"},{"key":"bib53","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-015-0600-x","article-title":"A coherent approach for analysis of the Illumina Humanmethylation450 Beadchip improves data quality and performance in epigenome-wide association studies","volume":"16","author":"Lehne","year":"2015","journal-title":"Genome Biology"},{"key":"bib54","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1037\/neu0000054","article-title":"Developmental gender differences in children in a virtual spatial memory task","volume":"28","author":"Le\u00f3n","year":"2014","journal-title":"Neuropsychology"},{"key":"bib55","doi-asserted-by":"publisher","first-page":"652","DOI":"10.1093\/eurpub\/ckaa213","article-title":"Dose\u2013response association between adult height and all-cause mortality: a systematic review and meta-analysis of cohort studies","volume":"31","author":"Li","year":"2021","journal-title":"European Journal of Public Health"},{"key":"bib56","doi-asserted-by":"publisher","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"L\u00f3pez-Ot\u00edn","year":"2013","journal-title":"Cell"},{"key":"bib57","doi-asserted-by":"publisher","first-page":"802","DOI":"10.1016\/j.cell.2016.07.031","article-title":"Metabolic control of longevity","volume":"166","author":"L\u00f3pez-Ot\u00edn","year":"2016","journal-title":"Cell"},{"key":"bib58","doi-asserted-by":"publisher","first-page":"303","DOI":"10.18632\/aging.101684","article-title":"DNA methylation GrimAge strongly predicts lifespan and healthspan. aging","volume":"11","author":"Lu","year":"2019","journal-title":"Aging"},{"key":"bib59","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-019-46338-x","article-title":"Telomere length in early childhood is associated with sex and ethnicity","volume":"9","author":"Ly","year":"2019","journal-title":"Scientific Reports"},{"key":"bib60","doi-asserted-by":"publisher","first-page":"623","DOI":"10.18632\/aging.203847","article-title":"A catalogue of omics biological ageing clocks reveals substantial commonality and associations with disease risk","volume":"14","author":"Macdonald-Dunlop","year":"2022","journal-title":"Aging"},{"key":"bib61","doi-asserted-by":"publisher","first-page":"382","DOI":"10.1093\/ije\/dyw029","article-title":"Cohort profile update: the Norwegian mother and child cohort study (MoBa)","volume":"45","author":"Magnus","year":"2016","journal-title":"International Journal of Epidemiology"},{"key":"bib62","doi-asserted-by":"publisher","DOI":"10.1136\/bmjopen-2017-021311","article-title":"Human Early Life Exposome (HELIX) study: a European population-based exposome cohort","volume":"8","author":"Maitre","year":"2018","journal-title":"BMJ Open"},{"key":"bib63","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.1093\/ije\/dyu277","article-title":"The epigenetic clock is correlated with physical and cognitive fitness in the Lothian Birth Cohort 1936","volume":"44","author":"Marioni","year":"2015","journal-title":"International Journal of Epidemiology"},{"key":"bib64","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-016-0689-0","article-title":"Maternal pre-pregnancy body mass index and newborn telomere length","volume":"14","author":"Martens","year":"2016","journal-title":"BMC Medicine"},{"key":"bib65","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2020.103164","article-title":"Newborn Telomere length predicts later life telomere length: tracking telomere length from birth to child- and adulthood","volume":"63","author":"Martens","year":"2021","journal-title":"EBioMedicine"},{"key":"bib66","doi-asserted-by":"publisher","first-page":"23329","DOI":"10.1073\/pnas.1820843116","article-title":"The PedBE clock accurately estimates DNA methylation age in pediatric buccal cells","volume":"117","author":"McEwen","year":"2020","journal-title":"PNAS"},{"key":"bib67","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1038\/nm.2014","article-title":"A crucial role for adipose tissue P53 in the regulation of insulin resistance","volume":"15","author":"Minamino","year":"2009","journal-title":"Nature Medicine"},{"key":"bib68","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-030-24970-0","volume-title":"Introduction, in Biomarkers of Human Aging","author":"Moskalev","year":"2019"},{"key":"bib69","doi-asserted-by":"publisher","first-page":"97","DOI":"10.1007\/s10440-006-9055-0","article-title":"The Exponentiated type distributions","volume":"92","author":"Nadarajah","year":"2006","journal-title":"Acta Applicandae Mathematicae"},{"key":"bib70","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-016-0301-7","article-title":"Obesity accelerates epigenetic aging in middle-aged but not in elderly individuals","volume":"9","author":"Nevalainen","year":"2017","journal-title":"Clinical Epigenetics"},{"key":"bib71","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1203\/00006450-200209000-00012","article-title":"Telomere length in the newborn","volume":"52","author":"Okuda","year":"2002","journal-title":"Pediatric Research"},{"key":"bib72","doi-asserted-by":"publisher","first-page":"1759","DOI":"10.1093\/bioinformatics\/btaa825","article-title":"Methylclock: a bioconductor package to estimate DNA methylation age","volume":"37","author":"Peleg\u00ed-Sis\u00f3","year":"2021","journal-title":"Bioinformatics"},{"key":"bib73","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-016-0228-z","article-title":"Epigenetic age acceleration predicts cancer, cardiovascular, and all-cause mortality in a German case cohort","volume":"8","author":"Perna","year":"2016","journal-title":"Clinical Epigenetics"},{"key":"bib74","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms9570","article-title":"The transcriptional landscape of age in human peripheral blood","volume":"6","author":"Peters","year":"2015","journal-title":"Nature Communications"},{"key":"bib75","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1007\/BF01537962","article-title":"A self-report measure of pubertal status: reliability, validity, and initial norms","volume":"17","author":"Petersen","year":"1988","journal-title":"Journal of Youth and Adolescence"},{"key":"bib76","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1126\/science.abe5017","article-title":"Daily energy expenditure through the human life course","volume":"373","author":"Pontzer","year":"2021","journal-title":"Science"},{"key":"bib77","doi-asserted-by":"publisher","first-page":"1324","DOI":"10.1183\/09031936.00080312","article-title":"Multi-ethnic reference values for spirometry for the 3\u201395-yr age range: the global lung function 2012 equations","volume":"40","author":"Quanjer","year":"2012","journal-title":"The European Respiratory Journal"},{"key":"bib78","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13149","article-title":"Determinants of accelerated metabolomic and epigenetic aging in a UK cohort","volume":"19","author":"Robinson","year":"2020","journal-title":"Aging Cell"},{"key":"bib79","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/s41576-022-00511-7","article-title":"Measuring biological age using omics data","volume":"23","author":"Rutledge","year":"2022","journal-title":"Nature Reviews. Genetics"},{"key":"bib80","doi-asserted-by":"publisher","first-page":"598","DOI":"10.1038\/s43587-021-00082-y","article-title":"An inflammatory aging clock (iAge) based on deep learning tracks multimorbidity, immunosenescence, frailty and cardiovascular aging","volume":"1","author":"Sayed","year":"2021","journal-title":"Nature Aging"},{"key":"bib81","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1079\/PHN2004556","article-title":"Food, youth and the Mediterranean diet in Spain. Development of KIDMED, Mediterranean Diet Quality Index in children and adolescents","volume":"7","author":"Serra-Majem","year":"2004","journal-title":"Public Health Nutrition"},{"key":"bib82","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a025163","article-title":"The emergence of geroscience as an interdisciplinary approach to the enhancement of health span and life span","volume":"6","author":"Sierra","year":"2016","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"bib83","doi-asserted-by":"publisher","first-page":"549","DOI":"10.1093\/ije\/dyw307","article-title":"The epigenetic clock and physical development during childhood and adolescence: longitudinal analysis from a UK birth cohort","volume":"46","author":"Simpkin","year":"2017","journal-title":"International Journal of Epidemiology"},{"key":"bib84","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1021\/acs.analchem.6b02930","article-title":"Interlaboratory reproducibility of a targeted metabolomics platform for analysis of human serum and plasma","volume":"89","author":"Siskos","year":"2017","journal-title":"Analytical Chemistry"},{"key":"bib85","doi-asserted-by":"publisher","DOI":"10.1186\/s13148-018-0528-6","article-title":"The epigenetic clock and pubertal, Neuroendocrine, psychiatric, and cognitive outcomes in adolescents","volume":"10","author":"Suarez","year":"2018","journal-title":"Clinical Epigenetics"},{"key":"bib86","first-page":"259","article-title":"Relationship between obesity and serum markers of oxidative stress and inflammation in Japanese","volume":"4","author":"Suzuki","year":"2003","journal-title":"Asian Pacific Journal of Cancer Prevention"},{"key":"bib87","doi-asserted-by":"publisher","first-page":"588","DOI":"10.1093\/gerona\/glx155","article-title":"Inverse association between height-increasing alleles and extreme longevity in Japanese women","volume":"73","author":"Tanisawa","year":"2018","journal-title":"The Journals of Gerontology"},{"key":"bib88","doi-asserted-by":"publisher","first-page":"541","DOI":"10.1161\/CIRCGEN.119.002610","article-title":"Metabolic age based on the BBMRI-NL (1)H-NMR Metabolomics repository as biomarker of age-related disease","volume":"13","author":"van den Akker","year":"2020","journal-title":"Circulation. Genomic and Precision Medicine"},{"key":"bib89","doi-asserted-by":"publisher","first-page":"3435","DOI":"10.1093\/bioinformatics\/btu566","article-title":"Methylaid: visual and interactive quality control of large Illumina 450K Datasets","volume":"30","author":"van Iterson","year":"2014","journal-title":"Bioinformatics"},{"key":"bib90","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1007\/s10654-019-00539-w","article-title":"Biography and biological capital","volume":"34","author":"Vineis","year":"2019","journal-title":"European Journal of Epidemiology"},{"key":"bib91","doi-asserted-by":"publisher","DOI":"10.1186\/s12916-020-01686-8","article-title":"In utero and childhood exposure to tobacco smoke and multi-layer molecular signatures in children","volume":"18","author":"Vives-Usano","year":"2020","journal-title":"BMC Medicine"},{"key":"bib92","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1289\/ehp.1307204","article-title":"The Human Early-Life Exposome (HELIX): project rationale and design","volume":"122","author":"Vrijheid","year":"2014","journal-title":"Environmental Health Perspectives"},{"key":"bib93","doi-asserted-by":"publisher","DOI":"10.1038\/tp.2015.71","article-title":"Telomere length is associated with oppositional defiant behavior and maternal clinical depression in Latino preschool children","volume":"5","author":"Wojcicki","year":"2015","journal-title":"Translational Psychiatry"},{"key":"bib94","doi-asserted-by":"publisher","first-page":"978","DOI":"10.1093\/ije\/dys112","article-title":"Cohort profile: The Born in Bradford multi-ethnic family cohort study","volume":"42","author":"Wright","year":"2013","journal-title":"International Journal of Epidemiology"},{"key":"bib95","doi-asserted-by":"publisher","DOI":"10.1186\/s13073-019-0667-1","article-title":"Improved precision of epigenetic clock estimates across tissues and its implication for biological ageing","volume":"11","author":"Zhang","year":"2019","journal-title":"Genome Medicine"},{"key":"bib96","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1111\/j.1467-9868.2005.00503.x","article-title":"Regularization and variable selection via the elastic net","volume":"67","author":"Zou","year":"2005","journal-title":"Journal of the Royal Statistical Society Series B"}],"container-title":["eLife"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/cdn.elifesciences.org\/articles\/85104\/elife-85104-v2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/cdn.elifesciences.org\/articles\/85104\/elife-85104-v2.xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/elifesciences.org\/articles\/85104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,11]],"date-time":"2023-10-11T21:13:12Z","timestamp":1697058792000},"score":1,"resource":{"primary":{"URL":"https:\/\/elifesciences.org\/articles\/85104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,6,6]]},"references-count":96,"alternative-id":["10.7554\/eLife.85104"],"URL":"https:\/\/doi.org\/10.7554\/elife.85104","archive":["CLOCKSS"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.01.23.23284901","asserted-by":"subject"},{"id-type":"doi","id":"10.1101\/2023.01.23.23284901","asserted-by":"object"}],"has-review":[{"id-type":"doi","id":"10.7554\/eLife.85104.sa2","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.85104.sa0","asserted-by":"object"},{"id-type":"doi","id":"10.7554\/eLife.85104.sa1","asserted-by":"object"}]},"ISSN":["2050-084X"],"issn-type":[{"value":"2050-084X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,6,6]]},"assertion":[{"value":"single anonymised","name":"peer_review_transparency","label":"Peer review transparency","group":{"name":"peer_review_taxonomy"}},{"value":"other reviewer(s), editor","name":"peer_review_interaction","label":"Peer review interaction","group":{"name":"peer_review_taxonomy"}},{"value":"review summaries, review reports, author\/editor communication, reviewer identities reviewer opt in, editor identities","name":"peer_review_published","label":"Peer review published","group":{"name":"peer_review_taxonomy"}},{"value":"open (sign in with ORCID iD required)","name":"post_publication_commenting","label":"Post publication commenting","group":{"name":"post_publication_commenting"}}],"article-number":"e85104"}}