Association of mitochondrial DNA levels with frailty and all-cause mortality.
Association of mitochondrial DNA levels with frailty and all-cause mortality.
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线粒体 DNA 水平与虚弱和全因死亡率的关联。
DOI：
10.1007/s00109-014-1233-3
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发表时间：
2015-02
影响因子：
4.7
通讯作者：
Arking, Dan E.
中科院分区：
文献类型：
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作者：
Ashar, Foram N.;Moes, Anna;Moore, Ann Z.;Grove, Megan L.;Chaves, Paulo H. M.;Coresh, Josef;Newman, Anne B.;Matteini, Amy M.;Bandeen-Roche, Karen;Boerwinkle, Eric;Walston, Jeremy D.;Arking, Dan E.
线粒体功能随着年龄的增长而改变，线粒体DNA （mtDNA）的变异调节了几种与年龄相关的疾病状态的风险。然而，mtDNA拷贝数（一种反映线粒体消耗、能量储备和氧化应激的现成标记）与普通人群衰老和死亡率的关系尚未得到解决。为了评估mtDNA拷贝数与两个主要结局——普遍虚弱和全因死亡率之间的关系，我们利用了来自两个多中心、多种族、基于社区的前瞻性研究参与者的数据——心血管健康研究（CHS）（1989-2006）和社区动脉粥样硬化风险研究（ARIC）（1987-2013）。共有4892名来自CHS的参与者（43.3%的男性）和11509名来自ARIC的参与者（44.9%的男性）自认为是白人或黑人。mtDNA拷贝数，目标性状，在CHS中使用基于qpcr的方法，在ARIC中使用基于阵列的方法，从两个队列的参与者的全血中分离DNA。在种族分层荟萃分析中，我们观察到mtDNA拷贝数与年龄呈显著负相关，女性的mtDNA拷贝数高于男性。mtDNA拷贝数较低也与CHS白人参与者普遍虚弱显著相关（OR 0.91, 95% CI, 0.85-0.97）。此外，mtDNA拷贝数是年龄和性别调整后的全因死亡率的一个强有力的独立预测因子，对来自两个队列的16401名参与者进行种族分层分析，mtDNA拷贝数最低五分位数相对于最高五分位数的合并风险比为1.47 （95% CI, 1.33-1.62）。
Mitochondrial function is altered with age, and variants in mitochondrial DNA (mtDNA) modulate risk for several age-related disease states. However, the association of mtDNA copy number, a readily available marker which reflects mitochondrial depletion, energy reserves and oxidative stress, on aging and mortality in the general population has not been addressed. To assess the association between mtDNA copy number and two primary outcomes—prevalent frailty and all-cause mortality, we utilize data from participants were from two multi-center, multi-ethnic, community-based, prospective studies—the Cardiovascular Health Study (CHS) (1989-2006) and the Atherosclerosis Risk in Communities study (ARIC) (1987-2013). A total of 4,892 participants (43.3% men) from CHS and 11,509 participants (44.9% men) from ARIC self-identifying as white or black were included in the analysis. mtDNA copy number, the trait of interest, was measured using a qPCR-based method in CHS and an array-based method in ARIC from DNA isolated from whole blood in participants from both cohorts. In race-stratified meta-analyses, we observe a significant inverse association of mtDNA copy number with age, and higher mtDNA copy number in women relative to men. Lower mtDNA copy number was also significantly associated with prevalent frailty in white participants from CHS (OR 0.91, 95% CI, 0.85-0.97). Additionally, mtDNA copy number was a strong independent predictor of all-cause mortality in an age and sex-adjusted, race-stratified analysis of 16,401 participants from both cohorts with a pooled hazard ratio of 1.47 (95% CI, 1.33-1.62) for the lowest quintile of mtDNA copy number relative to the highest quintile.
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影响因子：
5.3
作者：
Mengel-From, Jonas;Thinggaard, Mikael;Dalgard, Christine;Kyvik, Kirsten Ohm;Christensen, Kaare;Christiansen, Lene
通讯作者：
Christiansen, Lene
影响因子：
3.7
作者：
Arking, Dan E.;Reinier, Kyndaron;Chugh, Sumeet S.
通讯作者：
Chugh, Sumeet S.
DOI：
10.1111/j.1532-5415.1972.tb00787.x
发表时间：
1972-01-01
影响因子：
6.3
作者：
HARMAN, D
通讯作者：
HARMAN, D
影响因子：
3.7
作者：
Moore AZ;Biggs ML;Matteini A;O'Connor A;McGuire S;Beamer BA;Fallin MD;Fried LP;Walston J;Chakravarti A;Arking DE
通讯作者：
Arking DE
影响因子：
--
作者：
Kenney, M. Cristina;Hertzog, Dieter;Udar, Nitin
通讯作者：
Udar, Nitin