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Mitochondrial DNA Copy Number Correlates with Self-Rated Health in Older Adults

Mitochondria are the evolved descendants of ancient symbiotic bacteria. They act as the power plants of the cell, responsible for providing chemical energy store molecules (adenosine triphosphate, ATP) that power cellular operations. Each cell contains a herd of mitochondria, replicating like bacteria and culled by quality control mechanisms when they become damaged and dysfunctional. As a legacy of their ancient bacterial origins, mitochondria contain copies of a small circular genome, the mitochondrial DNA. This genome encodes the few important genes necessary for mitochondrial structure and function that have not migrated to the cell nucleus over the course of evolution.

As is the case for all cellular mechanisms and structures, this intricate set of nested systems falls apart with aging. Mitochondria become ragged and dysfunctional throughout the body, their ability to generate ATP declines, and energy-hungry tissues like the brain and muscles suffer for it. Further, mitochondrial DNA becomes damaged by oxidative molecules, and in a small fraction of cases that damage produces mitochondria that are both malfunctioning and resistant to quality control. These broken mitochondria take over cells, making the cells themselves dysfunctional, leading to the mass export of harmful oxididative molecules into tissues and the bloodstream.

In this context, the number of copies of mitochondrial DNA found in cells, the copy number, has been shown to correlate to several measures of aging. To start with, the copy number declines with age. Further, the copy number is associated with telomere length, and more importantly with frailty and mortality risk. More interestingly, researchers have demonstrated that artificially forcing an increase in mitochondrial DNA copy number slows vascular aging in mice. Copy number isn't quite a count of mitochondria, or quite an assessment of mitochondrial function, it should be noted - mitochondria tend to promiscuously pass around their component parts, and any given mitochondrion might well have multiple copies of its genome. But it is at least loosely related.

It remains to be determined as to whether this all boils down to delivery of ATP, and the consequences of too little ATP for cells to function to their full capacity, or whether a broader and more indirect set of mechanisms are involved. Biology is enormously complex, and simplicity in any aspect of it is usually only an illusion. The reality always turns out to be more layered, confusing, and contradictory than we'd like it to be. The research noted here presents another correlation between health and mitochondrial copy number to add to those noted above, but firm answers to the questions raised still lie ahead.

Association of mitochondrial DNA copy number with self-rated health status

The role of the mitochondria has been receiving increasing attention in various health-related research supported by substantial evidence of a causative link between mitochondrial dysfunction and aging and health outcomes. Additionally, it is suggested that the link between inflammation and health conditions may be modulated by mitochondrial dysfunction. Since mitochondrial function is regulated by both the nuclear and mitochondrial genomes, it has been proposed that variation in mitochondrial DNA (mtDNA), an understudied human genome compared to the nuclear genome, may also play an important role in these health conditions.

Additionally, mtDNA mutations are accumulated over a lifetime with several risk factors associated with adverse outcomes, such as smoking exposure, leading to a faster accumulation rate. mtDNA copy number has been suggested to be a link between risk factors and health outcomes. For example, the association between smoking and lung cancer may be explained by changes in mtDNA copy numbers, due to increased oxidative stress and increased somatic mtDNA mutations caused by smoking, which leads to mitochondrial dysfunction.

In this study of 956 participants, we found that patients with higher mtDNA copy number in peripheral blood had better self-rated health independent of age. We also found that older patients had lower mtDNA copy numbers. Lastly, we found that men had lower mtDNA copy numbers than women. These findings are unique and differ from previous studies. These findings should continue to add to our understanding of the relationship of mtDNA copy number to self-rated health as well as the ongoing work on mtDNA and age and gender.

There has been limited previous work in determining the relationship between self-rated health and mtDNA copy number. In one previous study, 1067 combined peripheral blood samples were examined for such an association. The authors found a positive association between better self-rated health and higher mtDNA copy numbers. Our study provides further evidence of the relationship between lower self-rated health and lower mtDNA copy number.

In addition to this main finding, we found that older age was associated with lower mtDNA copy number. The relationship between age and mtDNA copy number depended upon the patient's sex. Previous studies, looking at different tissue types, also showed an age-related decline in mtDNA copy number, but the role of sex and mtDNA copy number differs in our study from previous studies. We found that men had a lower copy number than women. Biologically, the changes in the number of the mitochondria DNA with age may reflect an increase in both inflammation and oxidative stress. The oxidative stress from free radicals may be responsible for the aging process which is tied to the mitochondria.

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Posted by: Morpheus at December 8th, 2018 8:51 PM

This blog tipped me of regarding MitoQ a few years ago. A substance that will not in any way cure aging I know.
But supplementing it certainly gives me some kind of increased vitality, probably due to increased mitochondrial function.
I tried quite a few supplements in full belief but placebo never did give me something like this.

Imagine the feeling of vitality that would come from partial or full rejuvenation treatment.

Posted by: arren brandt at December 10th, 2018 4:57 AM

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