Mitochondrial DNA variants and their impact on epigenetic and biological aging in young adulthood.

IF 5.8 1区医学 Q1 PSYCHIATRY Translational Psychiatry Pub Date : 2025-01-22 DOI:10.1038/s41398-025-03235-4

Klara Mareckova, Ana Paula Mendes-Silva, Martin Jáni, Anna Pacinkova, Pavel Piler, Vanessa F Gonçalves, Yuliya S Nikolova

{"title":"Mitochondrial DNA variants and their impact on epigenetic and biological aging in young adulthood.","authors":"Klara Mareckova, Ana Paula Mendes-Silva, Martin Jáni, Anna Pacinkova, Pavel Piler, Vanessa F Gonçalves, Yuliya S Nikolova","doi":"10.1038/s41398-025-03235-4","DOIUrl":null,"url":null,"abstract":"<p><p>The pace of biological aging varies between people independently of chronological age and mitochondria dysfunction is a key hallmark of biological aging. We hypothesized that higher functional impact (FI) score of mitochondrial DNA (mtDNA) variants might contribute to premature aging and tested the relationships between a novel FI score of mtDNA variants and epigenetic and biological aging in young adulthood. A total of 81 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort had good quality genetic data as well as blood-based markers to estimate biological aging in the late 20. A subset of these participants (n = 69) also had epigenetic data to estimate epigenetic aging in the early 20s using Horvath's epigenetic clock. The novel FI score was calculated based on 7 potentially pathogenic mtDNA variants. Greater FI score of mtDNA variants was associated with older epigenetic age in the early 20s and older biological age in the late 20s. These medium to large effects were independent of sex, current BMI, cigarette smoking, cannabis, and alcohol use. These findings suggest that elevated FI score of mtDNA variants might contribute to premature aging in young adulthood.</p>","PeriodicalId":23278,"journal":{"name":"Translational Psychiatry","volume":"15 1","pages":"16"},"PeriodicalIF":5.8000,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751369/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Translational Psychiatry","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1038/s41398-025-03235-4","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PSYCHIATRY","Score":null,"Total":0}

引用次数: 0

Abstract

The pace of biological aging varies between people independently of chronological age and mitochondria dysfunction is a key hallmark of biological aging. We hypothesized that higher functional impact (FI) score of mitochondrial DNA (mtDNA) variants might contribute to premature aging and tested the relationships between a novel FI score of mtDNA variants and epigenetic and biological aging in young adulthood. A total of 81 participants from the European Longitudinal Study of Pregnancy and Childhood (ELSPAC) prenatal birth cohort had good quality genetic data as well as blood-based markers to estimate biological aging in the late 20. A subset of these participants (n = 69) also had epigenetic data to estimate epigenetic aging in the early 20s using Horvath's epigenetic clock. The novel FI score was calculated based on 7 potentially pathogenic mtDNA variants. Greater FI score of mtDNA variants was associated with older epigenetic age in the early 20s and older biological age in the late 20s. These medium to large effects were independent of sex, current BMI, cigarette smoking, cannabis, and alcohol use. These findings suggest that elevated FI score of mtDNA variants might contribute to premature aging in young adulthood.

查看原文

微信好友朋友圈 QQ好友复制链接

本刊更多论文

线粒体DNA变异及其对青年期表观遗传和生物学衰老的影响。

生物衰老的速度因人而异，与实际年龄无关，线粒体功能障碍是生物衰老的一个关键标志。我们假设线粒体DNA （mtDNA）变异较高的功能影响（FI）评分可能导致过早衰老，并测试了线粒体DNA变异的新FI评分与青年期表观遗传和生物学衰老之间的关系。来自欧洲妊娠和儿童纵向研究（ELSPAC）产前出生队列的81名参与者具有高质量的遗传数据以及基于血液的标记物来估计20年代后期的生物衰老。这些参与者的一个子集（n = 69）也有表观遗传数据，使用Horvath的表观遗传时钟来估计20岁出头的表观遗传衰老。新的FI评分是根据7种潜在致病性mtDNA变体计算的。mtDNA变异的FI评分越高，与20岁出头的表观遗传年龄和20岁后期的生物学年龄有关。这些中等到较大的影响与性别、目前的BMI、吸烟、大麻和饮酒无关。这些发现表明，mtDNA变异的FI评分升高可能导致青年期过早衰老。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文去求助

来源期刊

Translational Psychiatry PSYCHIATRY-

CiteScore

11.50

自引率

2.90%

发文量

484

审稿时长

23 weeks

期刊介绍： Psychiatry has suffered tremendously by the limited translational pipeline. Nobel laureate Julius Axelrod''s discovery in 1961 of monoamine reuptake by pre-synaptic neurons still forms the basis of contemporary antidepressant treatment. There is a grievous gap between the explosion of knowledge in neuroscience and conceptually novel treatments for our patients. Translational Psychiatry bridges this gap by fostering and highlighting the pathway from discovery to clinical applications, healthcare and global health. We view translation broadly as the full spectrum of work that marks the pathway from discovery to global health, inclusive. The steps of translation that are within the scope of Translational Psychiatry include (i) fundamental discovery, (ii) bench to bedside, (iii) bedside to clinical applications (clinical trials), (iv) translation to policy and health care guidelines, (v) assessment of health policy and usage, and (vi) global health. All areas of medical research, including — but not restricted to — molecular biology, genetics, pharmacology, imaging and epidemiology are welcome as they contribute to enhance the field of translational psychiatry.