{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T08:07:26Z","timestamp":1789027646494,"version":"build-2803163510"},"reference-count":71,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T00:00:00Z","timestamp":1788998400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Human Genetics"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Leukocyte telomere length (LTL) and epigenetic age acceleration (EAA) are widely studied biomarkers of biological aging, but their potential roles in healthspan remain unclear. We evaluated whether genetically proxied LTL and EAA show evidence of potential effects on healthspan.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a two\u2010sample Mendelian randomization study. Genetic instruments for LTL and four EAA biomarkers were obtained from published genome\u2010wide association studies, including up to 472,174 individuals for LTL and approximately 35,000 individuals for each EAA biomarker. Summary statistics for healthspan, defined as age at first diagnosis of any of eight major chronic conditions or death, were derived from 300,447 unrelated European\u2010ancestry participants in the UK Biobank. We used inverse\u2010variance\u2010weighted (IVW) models for the main analysis, with complementary MR estimators and sensitivity analyses to evaluate consistency, pleiotropy, instrument heterogeneity, and robustness.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Genetically proxied longer LTL was associated with extended healthspan (IVW\n                      <jats:italic>\u03b2<\/jats:italic>\n                      = 0.106; 95% CI: 0.054\u20130.158;\n                      <jats:italic>p<\/jats:italic>\n                      = 6.9\u00a0\u00d7\u00a010\n                      <jats:sup>\u22125<\/jats:sup>\n                      ). The association was robust across multiple sensitivity analyses. In contrast, the four genetically proxied EAA biomarkers did not show consistent MR evidence of an association with healthspan.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>These findings provide genetic evidence consistent with a potential role of LTL in healthspan, while providing little support for comparable associations involving the genetically proxied components of the evaluated EAA biomarkers. The findings do not exclude potential associations with environmentally or physiologically acquired EAA.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ahg.70057","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:23:30Z","timestamp":1789025010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Genetically Proxied Leukocyte Telomere Length and Epigenetic Age Acceleration in Relation to Healthspan: A Mendelian Randomization Study"],"prefix":"10.1111","author":[{"given":"Bowen","family":"Feng","sequence":"first","affiliation":[{"name":"The Hospital for Sick Children  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Yang","sequence":"additional","affiliation":[{"name":"Neuqua Valley High School  Naperville Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabriella R","family":"Wang","sequence":"additional","affiliation":[{"name":"Lake Forest Academy  Lake Forest Illinois USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu","family":"Hu","sequence":"additional","affiliation":[{"name":"Green River College  Auburn Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuntao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Developmental Neurobiology St. Jude Children's Research Hospital  Memphis Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,10]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2003.12.047"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010021\u201001035\u20103"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3246"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1530\/JOE\u201013\u20100201"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyl169"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph20136249"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.70159"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aab3389"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyv080"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyy101"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1177\/00333549141291S206"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13148\u2010016\u20100186\u20105"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyt179"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/EDE.0000000000000161"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.21998"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010019\u201014156\u20104"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyr036"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(03)12384\u20107"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.23470"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.13874"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010021\u201000944\u20106"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/geront\/gns052"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1093\/geront\/gnv130"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddu328"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010genet\u2010032918\u2010021921"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aaz6876"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2466"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2012.10.016"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.g4227"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.14.1194"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1007081"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.34408"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb\u20102013\u201014\u201010\u2010r115"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41576\u2010018\u20100004\u20103"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2014.10.039"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468\u20102667(19)30248\u20108"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph6010209"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101414"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2025.1555082"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2025.1602921"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/aging.101684"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010017\u201002697\u20105"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.4161\/epi.24008"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyw041"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010015\u20100584\u20106"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyac150"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059\u2010021\u201002398\u20109"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/nri3520"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.75374"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41380\u2010018\u20100259\u20102"},{"key":"e_1_2_11_52_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475\u20106773.2004.00243.x"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.genet.41.110306.130350"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1353\/cpr.2023.0011"},{"key":"e_1_2_11_55_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08982"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.amepre.2009.12.031"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.adf9382"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2021.18236"},{"key":"e_1_2_11_59_1","doi-asserted-by":"publisher","DOI":"10.1002\/gepi.22041"},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.5945"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.1038\/s43587\u2010021\u201000159\u20108"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010020\u201017312\u20103"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010073"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588\u2010018\u20100099\u20107"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1002\/oby.23927"},{"key":"e_1_2_11_66_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0112483"},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40795\u2010025\u201001212\u20100"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI19451"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1378\/chest.06\u20102179"},{"key":"e_1_2_11_70_1","doi-asserted-by":"publisher","DOI":"10.2217\/epi\u20102023\u20100343"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.1038\/s42003\u2010019\u20100290\u20100"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.1214\/19\u2010AOS1866"}],"container-title":["Annals of Human Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70057","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/ahg.70057","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/ahg.70057","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T07:23:32Z","timestamp":1789025012000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/ahg.70057"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,10]]},"references-count":71,"alternative-id":["10.1111\/ahg.70057"],"URL":"https:\/\/doi.org\/10.1111\/ahg.70057","archive":["Portico"],"relation":{},"ISSN":["0003-4800","1469-1809"],"issn-type":[{"value":"0003-4800","type":"print"},{"value":"1469-1809","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,10]]},"assertion":[{"value":"2026-02-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-19","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"ahg.70057"}}