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

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Abstract

The role of the mitochondria in disease, general health and aging has drawn much attention over the years. Several attempts have been made to describe how the numbers of mitochondria correlate with age, although with inconclusive results. In this study, the relative quantity 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, the estimated mean mitochondrial DNA copy number in 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 declined by −0.54 mtDNA 95 % CI (−0.63; −0.45) every year for those older than approximately 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 number had poorer outcomes in terms of cognitive performance, physical strength, self-rated health, and higher all-cause mortality than subjects with high mitochondrial DNA copy number, also when age was controlled for. The copy number mortality association can 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 better health and survival among elderly.

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Acknowledgments

We would like to thank Tinna Stevnsner for commenting on and discussing the paper and Steen Gregersen, Ulla Munk and Susanne Knudsen for technical assistance, colleagues at the epidemiology unit for collecting materials and participants for their contributions. The study was supported by a grant from the US National Institutes of Health/National Institute on Aging, Grant No. P01 AG08761; by a grant from The Danish Agency for Science, Technology and Innovation, Grant No. 09–070081, the European Union’s Seventh Framework Programme (FP7/2007-2011) under grant agreement n° 259679 and by grants from the Oda and Hans Svenningsens Foundation and Dagmar Marshalls Foundation. The Danish Aging Research Center is supported by a grant from the VELUX Foundation. The GEMINAKAR project was supported by grants from the Danish Medical Research Council, the Danish Diabetes Association, the NOVO Foundation and the Danish Heart Foundation. JMF initiated this study. MT contributed with statistical analysis. All co-authors contributed to the work by supplying materials or planning and writing this paper. All authors approved the final version. The authors declare no conflicts of interest.

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Correspondence to Jonas Mengel-From.

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Mengel-From, J., Thinggaard, M., Dalgård, C. et al. Mitochondrial DNA copy number in peripheral blood cells declines with age and is associated with general health among elderly. Hum Genet 133, 1149–1159 (2014). https://doi.org/10.1007/s00439-014-1458-9

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