ミトコンドリアDNA変異と病気との関連におけるコホート研究

私たちの身体には多くの共生生物がいます。
肺、皮膚、腸など外部環境との接触機会が多い部位には
身体の恒常性を保つために様々な微生物がいます。
そういった共生は細胞レベルでもあります。
細胞内にウィルスがいることもあると思いますが、
細胞が自身で生きる事ができるための重要な共生があります。
それがミトコンドリアです。
ミトコンドリア自体も生存に必要な遺伝情報が
細胞内の核にあるために細胞外で生命を維持することができません。
同様に細胞のタンパク質恒常性や代謝機能を
ミトコンドリアに委ねている事から
ミトコンドリアなしでは細胞は生きることができません。
従って、ミトコンドリアの異常は
細胞レベルの不健全性につながり、
人が抱える多くの病に関連している可能性があります。
ミトコンドリアの遺伝子であるmtDNAの変異と
以下の病気についての関連が示されています。
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〇癌(2-4)
〇アルツハイマー病(5)
〇パーキンソン病(6)
〇虚血性脳卒中(7)
〇心筋梗塞(8)
〇冠動脈疾患(9)
〇2型糖尿病(10,11)
---
Na Cai, Aurora Gomez-Duran(敬称略)らは
「The INTERVAL Study(12)」で行われた
16,220人の健康な人の遺伝情報からmtDNAの変異に着目し
その遺伝子変異とその後、20年以上にわたる追跡調査の中で
mtDNAの変異(N-formylmethionine (fMet)血中レベル)
と複数の疾患、死亡率について統計的に分析しています(1)。
このfMetは異物、損傷を受けた細胞から
アラームシグナルとして免疫系に認識されるため
慢性的な免疫反応惹起を起こす可能性もあります。
従って、mtDNAと免疫機能の相関を調べる事も
意味がある可能性があります。
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特にfMetレベルと相関が高いのは
循環器系に深く関わる疾患です。
〇心不全
〇動脈瘤
〇腎臓疾患
これらです。
また全体的な死亡率とも相関が高いです(Fig.6bより)。
---
従って、ミトコンドリアのfMetレベルは
予防医学としても意味がある事です。
このfMetレベルを参考に将来的なリスクや
予防的な日常生活の改善を提案する事に貢献します。
また、fMetレベルを薬剤や健康的な日常生活によって
後天的に下げる事ができるかどうかという視点もあります。

//Discussion//---
 In medicine, “one-size-fits-all” approach don’t exist due to highly heterogeneity, so we need to prepare the precise medicine for each patient. However, understanding aging and aging health can be broadly applied to many diseases including cardiovascular diseases, metabolic disease, cancer and neurological diseases. Basement of our health is health of each cell in the whole body. The cellular senescence is essential risk factor with aging. Therefore, maintaining healthy cycle/homeostasis of our cell as possible as possible also in aging condition is needed. Cell and mitochondria live together in our body, so mitochondria health is one of the basements. Mutation of mitochondria-related gene may lead to our disease essentially as indicated by Na Cai, Aurora Gomez-Duran, Ekaterina Yonova-Doing, Kousik Kundu, Annette I. Burgess, Zoe J. Golder, Claudia Calabrese, Marc J. Bonder, Marta Camacho, Rachael A. Lawson, Lixin Li, Caroline H. Williams-Gray, ICICLE-PD Study Group, Emanuele Di Angelantonio, David J. Roberts, Nick A. Watkins, Willem H. Ouwehand, Adam S. Butterworth, Isobel D. Stewart, Maik Pietzner, Nick J. Wareham, Claudia Langenberg, John Danesh, Klaudia Walter, Peter M. Rothwell, Joanna M. M. Howson, Oliver Stegle, Patrick F. Chinnery & Nicole Soranzo(1). 
fMet demonstrated by them is alarm signal from cell functioning immune response. Hence, fMet level may be important biomarker in preventive medicine. However, we cannot receive medicine anytime and continuously in the condition without obvious disease, so considering healthy lifestyle is important in a prophylactic manner. In this viewpoint, association between mitochondria including fMet level and lifestyle hopes to be known. 
In SARS-CoV-2 pandemic, there are many barriers for healthy lifestyle. We need to build the healthy lifestyle both physically and mentally as early as possible after vaccination.  

(Reference)
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Na Cai, Aurora Gomez-Duran, Ekaterina Yonova-Doing, Kousik Kundu, Annette I. Burgess, Zoe J. Golder, Claudia Calabrese, Marc J. Bonder, Marta Camacho, Rachael A. Lawson, Lixin Li, Caroline H. Williams-Gray, ICICLE-PD Study Group, Emanuele Di Angelantonio, David J. Roberts, Nick A. Watkins, Willem H. Ouwehand, Adam S. Butterworth, Isobel D. Stewart, Maik Pietzner, Nick J. Wareham, Claudia Langenberg, John Danesh, Klaudia Walter, Peter M. Rothwell, Joanna M. M. Howson, Oliver Stegle, Patrick F. Chinnery & Nicole Soranzo 
Mitochondrial DNA variants modulate N-formylmethionine, proteostasis and risk of late-onset human diseases
Nature Medicine (2021)
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Author information
Author notes
These authors contributed equally: Na Cai, Aurora Gomez-Duran.
These authors jointly supervised this work: Joanna M. M. Howson, Oliver Stegle, Patrick F. Chinnery, Nicole Soranzo.
Affiliations
Human Genetics Department, Wellcome Sanger Institute (WT), Hinxton, UK
Na Cai, Kousik Kundu, Willem H. Ouwehand, John Danesh, Klaudia Walter & Nicole Soranzo
European Bioinformatics Institute (EMBL-EBI), Hinxton, UK
Na Cai, Marc J. Bonder & Oliver Stegle
Helmholtz Pioneer Campus, Helmholtz Zentrum München, Neuherberg, Germany
Na Cai
Department of Clinical Neurosciences, School of Clinical Medicine, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
Aurora Gomez-Duran, Zoe J. Golder, Claudia Calabrese, Marta Camacho, Caroline H. Williams-Gray & Patrick F. Chinnery
Medical Research Council Mitochondrial Biology Unit, University of Cambridge, Cambridge Biomedical Campus, Cambridge, UK
Aurora Gomez-Duran, Zoe J. Golder, Claudia Calabrese & Patrick F. Chinnery
Centro de Investigaciones Biológicas Margarita Salas, Consejo Superior de Investigaciones Científicas (CIB-CSIC), Madrid, Spain
Aurora Gomez-Duran
British Heart Foundation Cardiovascular Epidemiology Unit, Department of Primary Public Health and Primary Care, University of Cambridge, Cambridge, UK
Ekaterina Yonova-Doing, Emanuele Di Angelantonio, Adam S. Butterworth, John Danesh & Joanna M. M. Howson
Department of Genetics, Novo Nordisk Research Centre Oxford, Oxford, UK
Ekaterina Yonova-Doing & Joanna M. M. Howson
Wolfson Centre for Prevention of Stroke and Dementia, Nuffield Department of Clinical Neurosciences, University of Oxford, John Radcliffe Hospital, Oxford, UK
Annette I. Burgess, Lixin Li & Peter M. Rothwell
Division of Computational Genomics and Systems Genetics, German Cancer Research Center (DKFZ), Heidelberg, Germany
Marc J. Bonder & Oliver Stegle
Translational and Clinical Research Institute, Newcastle University, Newcastle, UK
Rachael A. Lawson
British Heart Foundation Centre of Research Excellence, University of Cambridge, Cambridge, UK
Emanuele Di Angelantonio, Willem H. Ouwehand, Adam S. Butterworth, John Danesh & Nicole Soranzo
National Institute for Health Research Blood and Transplant Research Unit in Donor Health and Genomics, University of Cambridge, Cambridge, UK
Emanuele Di Angelantonio, David J. Roberts, Adam S. Butterworth, John Danesh & Nicole Soranzo
Health Data Research UK Cambridge, Wellcome Genome Campus and University of Cambridge, Cambridge, UK
Emanuele Di Angelantonio, Adam S. Butterworth & John Danesh
NHS Blood and Transplant—Oxford Centre, John Radcliffe Hospital, Oxford, UK
David J. Roberts
Radcliffe Department of Medicine, University of Oxford, Oxford, UK
David J. Roberts
NHS Blood and Transplant, Cambridge Biomedical Campus, Cambridge, UK
Nick A. Watkins & Willem H. Ouwehand
Department of Haematology, University of Cambridge, Cambridge, UK
Willem H. Ouwehand & Nicole Soranzo
MRC Epidemiology Unit, University of Cambridge, Cambridge, UK
Isobel D. Stewart, Maik Pietzner, Nick J. Wareham & Claudia Langenberg
European Molecular Biology Laboratory, Heidelberg, Germany
Oliver Stegle
Genomics Research Centre, Human Technopole, Milan, Italy
Nicole Soranzo
Consortia
ICICLE-PD Study Group
Caroline H. Williams-Gray
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