S Alexandra Burt, S Mason Garrison, Xuanyu Lyu, Joseph L Rodgers, Sarah L Carroll, Ken R Smith, Michael D Hunter
{"title":"遗传mtDNA对长寿的贡献:来自1.76亿对亲属关系的扩展谱系的证据。","authors":"S Alexandra Burt, S Mason Garrison, Xuanyu Lyu, Joseph L Rodgers, Sarah L Carroll, Ken R Smith, Michael D Hunter","doi":"10.1016/j.ebiom.2025.105911","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Mitochondria are bacteria-like organelles with their own DNA (mtDNA) that exist in the cellular cytoplasm of almost every cell in the human body. Because mitochondria are critical for sustaining life, it follows that inherited mtDNA could be a key aetiologic element underlying longevity. Unfortunately, biometric approaches able to quantify heritable contributions of mtDNA have not been available.</p><p><strong>Methods: </strong>We directly leveraged the unique matrilineal inheritance pattern of mtDNA to estimate its effects on longevity (defined as the top 10% oldest survivors within their birth cohort). We employed the Utah Population Database (UPDB) to identify 176,348,110 unique kinship links amongst 1,018,929 individuals born between 1700 and 1925 with information on matrilineal versus patrilineal relatedness.</p><p><strong>Findings: </strong>Across 1st, 2nd, 3rd, 4th, and 5th degree kin, matrilineal relatives were more similar in their longevity outcomes than were non-maternal relatives. Variance component analyses indicated nuclear DNA heritability of 23-26% and mtDNA heritability of at least 5% - despite mtDNA constituting only ∼16.6 k base pairs (versus 2,875,002 k base pairs for nuclear DNA). Moreover, sharing the maternal line of a longevous relative translated to an average of 11.3 months extra years of life.</p><p><strong>Interpretation: </strong>Results collectively suggest that mtDNA may be an important element of unusually long lifespans.</p><p><strong>Funding: </strong>This project was supported by RF1-AG073189 and R01-AG022095 from the National Institute on Aging (NIA). We also acknowledge partial support through grant P30-CA2014 from the National Cancer Institute, University of Utah, and from the University of Utah's program in Personalized Health and Utah Clinical and Translational Science Institute.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"119 ","pages":"105911"},"PeriodicalIF":10.8000,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446199/pdf/","citationCount":"0","resultStr":"{\"title\":\"Contributions of inherited mtDNA to longevity: evidence from extended pedigrees with 176 million kinship pairs.\",\"authors\":\"S Alexandra Burt, S Mason Garrison, Xuanyu Lyu, Joseph L Rodgers, Sarah L Carroll, Ken R Smith, Michael D Hunter\",\"doi\":\"10.1016/j.ebiom.2025.105911\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Mitochondria are bacteria-like organelles with their own DNA (mtDNA) that exist in the cellular cytoplasm of almost every cell in the human body. Because mitochondria are critical for sustaining life, it follows that inherited mtDNA could be a key aetiologic element underlying longevity. Unfortunately, biometric approaches able to quantify heritable contributions of mtDNA have not been available.</p><p><strong>Methods: </strong>We directly leveraged the unique matrilineal inheritance pattern of mtDNA to estimate its effects on longevity (defined as the top 10% oldest survivors within their birth cohort). We employed the Utah Population Database (UPDB) to identify 176,348,110 unique kinship links amongst 1,018,929 individuals born between 1700 and 1925 with information on matrilineal versus patrilineal relatedness.</p><p><strong>Findings: </strong>Across 1st, 2nd, 3rd, 4th, and 5th degree kin, matrilineal relatives were more similar in their longevity outcomes than were non-maternal relatives. Variance component analyses indicated nuclear DNA heritability of 23-26% and mtDNA heritability of at least 5% - despite mtDNA constituting only ∼16.6 k base pairs (versus 2,875,002 k base pairs for nuclear DNA). Moreover, sharing the maternal line of a longevous relative translated to an average of 11.3 months extra years of life.</p><p><strong>Interpretation: </strong>Results collectively suggest that mtDNA may be an important element of unusually long lifespans.</p><p><strong>Funding: </strong>This project was supported by RF1-AG073189 and R01-AG022095 from the National Institute on Aging (NIA). We also acknowledge partial support through grant P30-CA2014 from the National Cancer Institute, University of Utah, and from the University of Utah's program in Personalized Health and Utah Clinical and Translational Science Institute.</p>\",\"PeriodicalId\":11494,\"journal\":{\"name\":\"EBioMedicine\",\"volume\":\"119 \",\"pages\":\"105911\"},\"PeriodicalIF\":10.8000,\"publicationDate\":\"2025-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12446199/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"EBioMedicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/j.ebiom.2025.105911\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2025/9/3 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"EBioMedicine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.ebiom.2025.105911","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/3 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Contributions of inherited mtDNA to longevity: evidence from extended pedigrees with 176 million kinship pairs.
Background: Mitochondria are bacteria-like organelles with their own DNA (mtDNA) that exist in the cellular cytoplasm of almost every cell in the human body. Because mitochondria are critical for sustaining life, it follows that inherited mtDNA could be a key aetiologic element underlying longevity. Unfortunately, biometric approaches able to quantify heritable contributions of mtDNA have not been available.
Methods: We directly leveraged the unique matrilineal inheritance pattern of mtDNA to estimate its effects on longevity (defined as the top 10% oldest survivors within their birth cohort). We employed the Utah Population Database (UPDB) to identify 176,348,110 unique kinship links amongst 1,018,929 individuals born between 1700 and 1925 with information on matrilineal versus patrilineal relatedness.
Findings: Across 1st, 2nd, 3rd, 4th, and 5th degree kin, matrilineal relatives were more similar in their longevity outcomes than were non-maternal relatives. Variance component analyses indicated nuclear DNA heritability of 23-26% and mtDNA heritability of at least 5% - despite mtDNA constituting only ∼16.6 k base pairs (versus 2,875,002 k base pairs for nuclear DNA). Moreover, sharing the maternal line of a longevous relative translated to an average of 11.3 months extra years of life.
Interpretation: Results collectively suggest that mtDNA may be an important element of unusually long lifespans.
Funding: This project was supported by RF1-AG073189 and R01-AG022095 from the National Institute on Aging (NIA). We also acknowledge partial support through grant P30-CA2014 from the National Cancer Institute, University of Utah, and from the University of Utah's program in Personalized Health and Utah Clinical and Translational Science Institute.
EBioMedicineBiochemistry, Genetics and Molecular Biology-General Biochemistry,Genetics and Molecular Biology
CiteScore
17.70
自引率
0.90%
发文量
579
审稿时长
5 weeks
期刊介绍:
eBioMedicine is a comprehensive biomedical research journal that covers a wide range of studies that are relevant to human health. Our focus is on original research that explores the fundamental factors influencing human health and disease, including the discovery of new therapeutic targets and treatments, the identification of biomarkers and diagnostic tools, and the investigation and modification of disease pathways and mechanisms. We welcome studies from any biomedical discipline that contribute to our understanding of disease and aim to improve human health.