Burt S Alexandra, Garrison S Mason, Lyu Xuanyu, Rodgers Joseph L, Carroll Sarah L, Smith Ken R, Hunter Michael D
Michigan State University, East Lansing, MI, USA.
Wake Forest University, Winston-Salem, NC, USA.
EBioMedicine. 2025 Sep;119:105911. doi: 10.1016/j.ebiom.2025.105911. Epub 2025 Sep 3.
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.
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.
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.
Results collectively suggest that mtDNA may be an important element of unusually long lifespans.
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.
线粒体是类似细菌的细胞器，拥有自身的DNA（mtDNA），存在于人体几乎每个细胞的细胞质中。由于线粒体对维持生命至关重要，因此遗传的mtDNA可能是长寿的关键病因要素。不幸的是，此前尚无能够量化mtDNA遗传贡献的生物统计学方法。
我们直接利用mtDNA独特的母系遗传模式来估计其对长寿（定义为出生队列中年龄最大的前10%幸存者）的影响。我们使用犹他人口数据库（UPDB），在1700年至1925年出生的1,018,929个人中识别出176,348,110个独特的亲属关系链接，并提供母系与父系亲缘关系的信息。
在一级、二级、三级、四级和五级亲属中，母系亲属的长寿结果比非母系亲属更为相似。方差成分分析表明，核DNA遗传率为23%-26%，mtDNA遗传率至少为5%——尽管mtDNA仅构成约16.6千碱基对（而核DNA为2,875,002千碱基对）。此外，拥有长寿亲属的母系血统平均可使寿命延长11.3个月。
研究结果共同表明，mtDNA可能是超长寿命的一个重要因素。
本项目由美国国立衰老研究所（NIA）的RF1-AG073189和R01-AG022095资助。我们还感谢美国国立癌症研究所、犹他大学以及犹他大学个性化健康项目和犹他临床与转化科学研究所提供的P30-CA2014部分资助。
