{"id":"https://openalex.org/W4404523398","doi":"https://doi.org/10.7554/elife.102447.1","title":"Early menarche and childbirth accelerate aging-related outcomes and age-related diseases: Evidence for antagonistic pleiotropy in humans","display_name":"Early menarche and childbirth accelerate aging-related outcomes and age-related diseases: Evidence for antagonistic pleiotropy in humans","publication_year":2024,"publication_date":"2024-11-19","ids":{"openalex":"https://openalex.org/W4404523398","doi":"https://doi.org/10.7554/elife.102447.1"},"language":"en","primary_location":{"id":"doi:10.7554/elife.102447.1","doi":"https://doi.org/10.7554/elife.102447.1","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.102447.1","pdf_url":null,"source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"eLife","raw_type":"posted-content"},"volume":null,"type":"preprint","indexed_in":["crossref","doaj"],"open_access":{"is_oa":true,"oa_status":"gold","oa_url":"https://doi.org/10.7554/elife.102447.1","any_repository_has_fulltext":false},"authorships":[{"author_position":"first","author":{"id":null,"display_name":"Yifan Xiang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Yifan Xiang","raw_affiliation_strings":["The Buck Institute for Research on Aging"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Buck Institute for Research on Aging","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023662472","display_name":"Vineeta Tanwar","orcid":"https://orcid.org/0000-0002-8507-2710","observed_orcids":["https://orcid.org/0000-0002-8507-2710"]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Vineeta Tanwar","raw_affiliation_strings":["The Buck Institute for Research on Aging"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Buck Institute for Research on Aging","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5074582149","display_name":"Parminder Pal Singh","orcid":"https://orcid.org/0000-0002-2851-6805","observed_orcids":["https://orcid.org/0000-0002-2851-6805"]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Parminder Singh","raw_affiliation_strings":["The Buck Institute for Research on Aging"],"raw_orcid":"https://orcid.org/0000-0002-2851-6805","affiliations":[{"raw_affiliation_string":"The Buck Institute for Research on Aging","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5107619185","display_name":"Lizellen La Follette","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Lizellen La Follette","raw_affiliation_strings":["The Buck Institute for Research on Aging"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"The Buck Institute for Research on Aging","institution_ids":["https://openalex.org/I1337826666"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5086548741","display_name":"Pankaj Kapahi","orcid":"https://orcid.org/0000-0002-5629-4947","observed_orcids":["https://orcid.org/0000-0002-5629-4947"]},"institutions":[{"id":"https://openalex.org/I1337826666","display_name":"Buck Institute for Research on Aging","ror":"https://ror.org/050sv4x28","country_code":"US","type":"nonprofit","lineage":["https://openalex.org/I1337826666"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Pankaj Kapahi","raw_affiliation_strings":["The Buck Institute for Research on Aging"],"raw_orcid":"https://orcid.org/0000-0002-5629-4947","affiliations":[{"raw_affiliation_string":"The Buck Institute for Research on Aging","institution_ids":["https://openalex.org/I1337826666"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":[],"corresponding_institution_ids":["https://openalex.org/I1337826666"],"apc_list":{"value":3000,"currency":"USD","value_usd":2500},"apc_paid":{"value":3000,"currency":"USD","value_usd":2500},"fwci":null,"has_fulltext":false,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.42719998955726624,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.42719998955726624,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10676","display_name":"Genetics, Aging, and Longevity in Model Organisms","score":0.42239999771118164,"subfield":{"id":"https://openalex.org/subfields/1302","display_name":"Aging"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11764","display_name":"Evolution and Genetic Dynamics","score":0.01810000091791153,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/antagonistic-pleiotropy","display_name":"antagonistic pleiotropy","score":0.9660000205039978},{"id":"https://openalex.org/keywords/theories-of-aging","display_name":"theories of aging","score":0.7409999966621399},{"id":"https://openalex.org/keywords/age-at-menarche","display_name":"age at menarche","score":0.8050000071525574},{"id":"https://openalex.org/keywords/first-birth","display_name":"first birth","score":0.7459999918937683},{"id":"https://openalex.org/keywords/age-at-menopause","display_name":"age at menopause","score":0.6930000185966492},{"id":"https://openalex.org/keywords/frailty","display_name":"frailty","score":0.9120000004768372},{"id":"https://openalex.org/keywords/epigenetic-aging","display_name":"epigenetic aging","score":0.972000002861023},{"id":"https://openalex.org/keywords/facial-aging","display_name":"facial aging","score":0.796999990940094},{"id":"https://openalex.org/keywords/age-related-diseases","display_name":"age-related diseases","score":0.8989999890327454},{"id":"https://openalex.org/keywords/late-onset-alzheimer-s-disease","display_name":"late-onset Alzheimer's disease","score":0.9589999914169312},{"id":"https://openalex.org/keywords/type-2-diabetes","display_name":"type 2 diabetes","score":1.0},{"id":"https://openalex.org/keywords/heart-failure","display_name":"heart failure","score":0.7820000052452087},{"id":"https://openalex.org/keywords/essential-hypertension","display_name":"essential hypertension","score":0.8730000257492065},{"id":"https://openalex.org/keywords/chronic-obstructive-pulmonary-disease","display_name":"chronic obstructive pulmonary disease","score":0.9940000176429749},{"id":"https://openalex.org/keywords/obesity","display_name":"obesity","score":0.9829999804496765},{"id":"https://openalex.org/keywords/body-mass-index","display_name":"body mass index","score":0.8500000238418579},{"id":"https://openalex.org/keywords/thrifty-gene-hypothesis","display_name":"thrifty gene hypothesis","score":0.8809999823570251},{"id":"https://openalex.org/keywords/insulin-like-growth-factor-i","display_name":"insulin-like growth factor I","score":0.9419999718666077},{"id":"https://openalex.org/keywords/growth-hormone","display_name":"growth hormone","score":0.9490000009536743},{"id":"https://openalex.org/keywords/ampk","display_name":"AMPK","score":0.9139999747276306},{"id":"https://openalex.org/keywords/mtor-signaling","display_name":"mTOR signaling","score":0.9850000143051147},{"id":"https://openalex.org/keywords/women-s-reproductive-health","display_name":"women's reproductive health","score":0.6660000085830688},{"id":"https://openalex.org/keywords/mendelian-randomization","display_name":"Mendelian randomization","score":0.6629999876022339}],"concepts":[{"id":"https://openalex.org/C26207810","wikidata":"https://www.wikidata.org/wiki/Q1134884","display_name":"Pleiotropy","level":4,"score":0.8519898653030396},{"id":"https://openalex.org/C2779703513","wikidata":"https://www.wikidata.org/wiki/Q34581","display_name":"Childbirth","level":3,"score":0.736395001411438},{"id":"https://openalex.org/C4258228","wikidata":"https://www.wikidata.org/wiki/Q492514","display_name":"Menarche","level":2,"score":0.6251451373100281},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.44027066230773926},{"id":"https://openalex.org/C2779234561","wikidata":"https://www.wikidata.org/wiki/Q11995","display_name":"Pregnancy","level":2,"score":0.36633092164993286},{"id":"https://openalex.org/C15744967","wikidata":"https://www.wikidata.org/wiki/Q9418","display_name":"Psychology","level":0,"score":0.34901970624923706},{"id":"https://openalex.org/C149923435","wikidata":"https://www.wikidata.org/wiki/Q37732","display_name":"Demography","level":1,"score":0.3421916961669922},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.2550022006034851},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.2063198685646057},{"id":"https://openalex.org/C134018914","wikidata":"https://www.wikidata.org/wiki/Q162606","display_name":"Endocrinology","level":1,"score":0.19857576489448547},{"id":"https://openalex.org/C127716648","wikidata":"https://www.wikidata.org/wiki/Q104053","display_name":"Phenotype","level":3,"score":0.07474339008331299},{"id":"https://openalex.org/C144024400","wikidata":"https://www.wikidata.org/wiki/Q21201","display_name":"Sociology","level":0,"score":0.07387018203735352},{"id":"https://openalex.org/C104317684","wikidata":"https://www.wikidata.org/wiki/Q7187","display_name":"Gene","level":2,"score":0.0}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.7554/elife.102447.1","doi":"https://doi.org/10.7554/elife.102447.1","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.102447.1","pdf_url":null,"source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"eLife","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.7554/elife.102447.1","doi":"https://doi.org/10.7554/elife.102447.1","is_oa":true,"landing_page_url":"https://doi.org/10.7554/elife.102447.1","pdf_url":null,"source":{"id":"https://openalex.org/S1336409049","display_name":"eLife","issn_l":"2050-084X","issn":["2050-084X"],"is_oa":true,"is_in_doaj":true,"is_core":true,"listed_in":["anvur-scientific","cwts-core","doaj","dongbi-a","jufo-2","ki-jl-2","medline","norway-2","oarl","poland-200","russia-white-list-1","vabb-shw"],"host_organization":"https://openalex.org/P4310311710","host_organization_name":"eLife Sciences Publications Ltd","host_organization_lineage":["https://openalex.org/P4310311710"],"host_organization_lineage_names":["eLife Sciences Publications Ltd"],"type":"journal"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"acceptedVersion","is_accepted":true,"is_published":false,"raw_source_name":"eLife","raw_type":"posted-content"},"sustainable_development_goals":[{"score":1.0,"display_name":"Good health and well-being","id":"https://metadata.un.org/sdg/3"}],"sustainable_development_goals_aurora":[],"study_designs":[{"display_name":"Observational Study","id":"https://openalex.org/study-designs/observational-study"}],"awards":[{"id":"https://openalex.org/G4377785487","display_name":"Role of Circadian Clocks in Aging using Drosophila","funder_award_id":"R01AG045835","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"},{"id":"https://openalex.org/G6142202875","display_name":"Methylglyoxal drives astrocyte senescence to mediate neurodegeneration in Alzheimer's disease","funder_award_id":"R01AG068288","funder_id":"https://openalex.org/F4320337337","funder_display_name":"National Institute on Aging"}],"funders":[{"id":"https://openalex.org/F1063528218","display_name":"Hevolution Foundation","ror":"https://ror.org/00kgc7526"},{"id":"https://openalex.org/F4320306380","display_name":"Larry L. Hillblom Foundation","ror":"https://ror.org/00br6vq85"},{"id":"https://openalex.org/F4320337337","display_name":"National Institute on Aging","ror":"https://ror.org/049v75w11"}],"has_content":{"pdf":false,"grobid_xml":false},"content_urls":null,"referenced_works_count":89,"referenced_works":["https://openalex.org/W129795565","https://openalex.org/W1966537913","https://openalex.org/W1968259483","https://openalex.org/W1977230392","https://openalex.org/W1986753065","https://openalex.org/W1987305776","https://openalex.org/W1992144214","https://openalex.org/W2039153962","https://openalex.org/W2041800714","https://openalex.org/W2066113694","https://openalex.org/W2069044303","https://openalex.org/W2071436643","https://openalex.org/W2080282563","https://openalex.org/W2089059447","https://openalex.org/W2096541451","https://openalex.org/W2103781339","https://openalex.org/W2108271874","https://openalex.org/W2114512247","https://openalex.org/W2115053548","https://openalex.org/W2123031408","https://openalex.org/W2126622398","https://openalex.org/W2126775184","https://openalex.org/W2128736149","https://openalex.org/W2132608925","https://openalex.org/W2147409481","https://openalex.org/W2162143298","https://openalex.org/W2162898572","https://openalex.org/W2170318101","https://openalex.org/W2243864136","https://openalex.org/W2341019791","https://openalex.org/W2341828758","https://openalex.org/W2342100485","https://openalex.org/W2398690791","https://openalex.org/W2419320951","https://openalex.org/W2589088833","https://openalex.org/W2596578076","https://openalex.org/W2599928462","https://openalex.org/W2605895898","https://openalex.org/W2726439135","https://openalex.org/W2767891136","https://openalex.org/W2771230199","https://openalex.org/W2789315525","https://openalex.org/W2809193491","https://openalex.org/W2886497950","https://openalex.org/W2894859047","https://openalex.org/W2912285780","https://openalex.org/W2916749909","https://openalex.org/W2950392934","https://openalex.org/W2950598813","https://openalex.org/W2952013316","https://openalex.org/W2953226929","https://openalex.org/W2953249511","https://openalex.org/W2955177623","https://openalex.org/W2995440951","https://openalex.org/W3010088053","https://openalex.org/W3033197621","https://openalex.org/W3091149362","https://openalex.org/W3102269442","https://openalex.org/W3124408980","https://openalex.org/W3139396125","https://openalex.org/W3140403198","https://openalex.org/W3167573237","https://openalex.org/W3176120982","https://openalex.org/W3177165321","https://openalex.org/W3193192778","https://openalex.org/W3194731752","https://openalex.org/W3201544313","https://openalex.org/W3202209876","https://openalex.org/W3202212354","https://openalex.org/W3203318770","https://openalex.org/W3209744789","https://openalex.org/W4207019201","https://openalex.org/W4244095134","https://openalex.org/W4280529260","https://openalex.org/W4282920272","https://openalex.org/W4282939243","https://openalex.org/W4315853223","https://openalex.org/W4321597359","https://openalex.org/W4361190285","https://openalex.org/W4362521982","https://openalex.org/W4376274039","https://openalex.org/W4384202290","https://openalex.org/W4385347917","https://openalex.org/W4386470247","https://openalex.org/W4388523237","https://openalex.org/W4389058414","https://openalex.org/W4389475520","https://openalex.org/W4390202203","https://openalex.org/W4392477236"],"related_works":["https://openalex.org/W4392930885","https://openalex.org/W4220689928","https://openalex.org/W7165737608","https://openalex.org/W3011057199","https://openalex.org/W4417497883","https://openalex.org/W7135657268","https://openalex.org/W3035446435","https://openalex.org/W2626849965","https://openalex.org/W3202972655","https://openalex.org/W2623683470"],"abstract_inverted_index":{"Abstract":[0],"Aging":[1],"can":[2],"be":[3],"understood":[4],"as":[5,224,237],"a":[6,93,225],"consequence":[7],"of":[8,12,24,58,96,125,131,145,166,182,202,233,255],"the":[9,20,31,120,123,129,138,155,164,172,180,185,230,253,256,264,272,282,290],"declining":[10],"force":[11],"natural":[13],"selection":[14],"with":[15,18,66,92,133,246],"age.":[16],"Consistent":[17],"this":[19],"antagonistic":[21,42,186,267],"pleiotropic":[22],"theory":[23],"aging":[25,28],"suggests":[26],"that":[27,33,55,152,197,288],"results":[29,150],"from":[30],"trade-offs":[32],"promote":[34],"early":[35,247,250],"growth":[36,212],"and":[37,78,112,128,158,169,178,215,241,278,297],"reproduction.":[38],"However,":[39],"evidence":[40],"for":[41,174,284],"pleiotropy":[43,187],"in":[44,137,206,228,244,260,262],"humans":[45],"is":[46],"largely":[47],"lacking.":[48],"Using":[49],"Mendelian":[50],"Randomization":[51],"(MR),":[52],"we":[53],"demonstrated":[54,151],"later":[56,76,83],"ages":[57],"menarche":[59,84,153,248],"or":[60,85,249],"first":[61,86],"childbirth":[62,87,159],"were":[63,88,204],"genetically":[64,90],"associated":[65,91],"longer":[67],"parental":[68],"lifespan,":[69],"decreased":[70],"frailty":[71],"index,":[72],"slower":[73],"epigenetic":[74],"aging,":[75],"menopause,":[77],"reduced":[79],"facial":[80],"aging.":[81,298],"Moreover,":[82],"also":[89,220],"lower":[94],"risk":[95,165,173,181,232],"several":[97,134,167],"age-related":[98,135,199],"diseases,":[99,168,235,280],"including":[100,210],"late-onset":[101],"Alzheimer\u2019s":[102],"disease":[103,116],"(LOAD),":[104],"type":[105,238],"2":[106,239],"diabetes,":[107,175],"heart":[108,176,242],"disease,":[109],"essential":[110],"hypertension,":[111],"chronic":[113],"obstructive":[114],"pulmonary":[115],"(COPD).":[117],"We":[118,189],"validated":[119],"associations":[121],"between":[122,275,293],"age":[124,156],"menarche,":[126],"childbirth,":[127],"number":[130],"childbirths":[132],"outcomes":[136],"UK":[139],"Biobank":[140],"by":[141],"conducting":[142],"regression":[143],"analysis":[144],"nearly":[146],"200,000":[147],"subjects.":[148],"Our":[149,218,269],"before":[154,160],"11":[157],"21":[161],"significantly":[162],"accelerated":[163],"almost":[170],"doubled":[171],"failure,":[177,243],"quadrupled":[179],"obesity,":[183],"supporting":[184],"theory.":[188],"identified":[190,221],"128":[191],"significant":[192],"single":[193],"nucleotide":[194],"polymorphisms":[195],"(SNPs)":[196],"influenced":[198],"outcomes,":[200],"some":[201],"which":[203],"involved":[205],"known":[207],"longevity":[208],"pathways,":[209],"IGF1,":[211],"hormone,":[213],"AMPK,":[214],"mTOR":[216],"signaling.":[217],"study":[219,270],"higher":[222],"BMI":[223],"mediating":[226],"factor":[227],"causing":[229],"increased":[231],"certain":[234],"such":[236],"diabetes":[240],"women":[245],"pregnancy,":[251],"emphasizing":[252,281],"importance":[254],"thrifty":[257],"gene":[258],"hypothesis":[259],"explaining":[261],"part":[263],"mechanisms":[265],"behind":[266],"pleiotropy.":[268],"highlights":[271],"complex":[273],"relationship":[274],"genetic":[276],"legacies":[277],"modern":[279],"need":[283],"gender-sensitive":[285],"healthcare":[286],"strategies":[287],"consider":[289],"unique":[291],"connections":[292],"female":[294],"reproductive":[295],"health":[296]},"counts_by_year":[],"updated_date":"2026-10-30T12:39:25.321706","created_date":"2024-11-20T00:00:00"}