Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly.

Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly.
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DOI:
10.1007/s00439-014-1458-9
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发表时间:
2014-09
期刊:
影响因子:
5.3
通讯作者:
Christiansen, Lene
Christiansen, Lene
中科院分区:
生物学2区
文献类型:
--
作者:
Mengel-From, Jonas;Thinggaard, Mikael;Dalgard, Christine;Kyvik, Kirsten Ohm;Christensen, Kaare;Christiansen, Lene

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线粒体在疾病、一般健康和衰老中的作用多年来引起了人们的极大关注。人们曾多次尝试描述线粒体的数量与年龄的关系,尽管结果并不确定。本研究采用聚合酶链式反应技术测量线粒体DNA与核DNA的相对数量,即线粒体DNA拷贝数,并将其作为衡量线粒体拷贝数的指标。在1,067名丹麦双胞胎和独生子女(18-93岁)中,大多数是老年人,估计18-48岁的外周血细胞线粒体DNA拷贝数相似(平均相对线粒体DNA含量:61.0;95%可信区间[52.1;69.9]),但−下降0.54mtDNA 95%CI[−0.63;然而,个体内纵向的年下降幅度是横断面分析中观察到的两倍以上(线粒体−含量下降:−1.27;95%可信区间[−1.71;−0.82])。与线粒体DNA拷贝数高的受试者相比,线粒体DNA拷贝数低的受试者在认知表现、体力、自评健康方面的结果更差,全因死亡率更高,在控制年龄的情况下也是如此。拷贝数死亡率与总体横断面样本中的纵向下降相比,有助于较小的下降。这项研究表明,血液中线粒体DNA拷贝数高与老年人的健康和生存状况有关。
The role of the mitochondria in disease, general health and aging has drawn much attention over the years. Several attemptshave been made to describe how the numbersof mitochondriacorrelate with age, although with inconclusive results. In this study, the relativequantity of mitochondrial DNA compared to nuclear DNA,i.e. the mitochondrial DNA copy number, was measured by PCR technology and used as a proxy for the content of mitochondria copies. In 1,067 Danish twins and singletons (18-93 years of age), with the majority being elderly individuals, theestimated mean mitochondrial DNA copy numberin peripheral blood cells was similar for those 18-48 years of age (mean relative mtDNA content: 61.0; 95% CI [52.1; 69.9]), but declinedby −0.54 mtDNA 95%CI [−0.63; −0.45] every year for those older thanapproximately 50 years of age.However, the longitudinal, yearly decline within an individual was more than twice as steep as observed in the cross-sectional analysis (decline of mtDNA content: −1.27; 95%CI [−1.71; −0.82]). Subjects with low mitochondrial DNA copy numberhad poorer outcomes in terms of cognitive performance, physical strength, self-rated health, andhigher all-cause mortality than subjects with high mitochondrial DNA copy number, also when age was controlled for.The copy numbermortality associationcan contribute to the smaller decline in a cross-sectional sample of the population compared to the individual,longitudinal decline. This study suggests that high mitochondrial DNA copy number in blood is associated with betterhealth and survival among elderly.
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