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

Abstract

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.

Restoring mitochondrial DNA copy number preserves mitochondrial function and delays vascular aging in mice

“…Cells contain many copies of the mitochondrial genome, and although mtCN declines with age in some cells (Mengel‐From et al., 2014), the rate of decline and the relationship between mtCN and mitochondrial respiration vary markedly between tissues (Wachsmuth, Hubner, Li, Madea & Stoneking, 2016). We examined mtCN relative to nuclear DNA in aortas from mice aged 8–72 wk.…”

Lengthening and shortening of plasma DNA in hepatocellular carcinoma patients

“…The median fractional concentration of plasma mitochondrial DNA was only 0.00045% in healthy subjects. This fractional concentration is relatively low, considering that the size of mitochondrial genome is 0.00053% of the size of the nuclear genome and there are 50-4,000 mitochondria per cell (46,47). The smaller size distribution and relatively low abundance of circulating mitochondrial DNA is likely to be due to the higher susceptibility of mitochondrial DNA to degradation due to the absence of histone protection.…”

“…Interestingly, the concentration of mitochondrial DNA in plasma was higher in the HCC patients compared with the healthy subjects. This may be due to the higher number of mitochondria in HCC cells or liver cells in general compared with hematopoietic cells, which are the major source of circulating DNA in healthy subjects (46)(47)(48). Quantitative analysis for plasma mitochondrial DNA might be useful for the detection of HCC.…”

Mitochondrial DNA copy number, but not haplogroup is associated with keratoconus in Han Chinese population

“…The mtDNA content is inversely associated with age (He et al, 2014;Mengel-From et al, 2014), and different tissues have different mitochondrial content (Benard et al, 2006). To exclude these effects, we measured the mtDNA copy number in 193 blood samples of patients (mean age ± SE, 20.58 ± 0.431) and 103 controls of matched age (mean age ± SE, 21.18 ± 0.213) from the first control cohort.…”