Mitochondrial DNA: A biomarker for frailty and death?

20.12.2014
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Mitochondria, the ‘powerhouses’ of the cell, contain their own DNA, separate from that found in the nucleus of cells. Now, scientists show that the amount of mitochondrial DNA found in people’s blood can predict how frail a person will be as they age.

Mitochondria, membrane bound organelles found in most eukaryotic cells, are known as ‘powerhouses’ of the cell, since they are the major source of energy production in the form of ATP (Adenosine Triphosphate).  These organelles, are constantly produced in cells and old and damaged mitochondria are continuously removed from cellular compartments. The number of mitochondria produced in each cell depends on the functions that cell is required to perform and how much energy it requires for these functions. Thus, greater numbers of mitochondria may be found in some cells compared to others. For example, muscle cells have the highest mitochondrial content than all other cells in the body, since they are required to provide energy for exercise and movement.

Mitochondria also contain their own genetic material, besides the chromosomal DNA that is packaged in the nucleus of cells. This DNA, known as mtDNA (mitochondrial DNA), has previously been implicated in aging and age-related diseases. In fact, there has been evidence showing that individuals with mitochondrial genetic diseases or mice that generate frequent mutations in mitochondrial DNA display phenotypes that resemble premature aging.

Now, researchers at John Hopkin’s University have found a direct correlation between the amount of mtDNA in people’s blood and symptoms of old age like weakness, weight loss and lethargy, which are altogether described as 'frailty'. In fact, their observations showed that the more mtDNA present, the less likely the person was to be frail when they were older.

 

Higher mtDNA levels protect from frailty and mortality

In order to assess the correlation between mitochondrial DNA levels and participant frailty, the scientists examined mtDNA copy numbers isolated from the blood of participants from two large human studies that contained a total number of 16,401 individuls, from both European and African descent.  Both these studies began in the late 1980s and the participants, who were aged from 45 and above, were tracked for the next 10 or 20 years to assess their health profiles.

Examining the mtDNA levels of participants that showed greater signs of frailty, revealed an average of 9% less mtDNA present than in nonfrail participants. In addition, participants that showed the lowest mtDNA levels in the population study were 31% more likely to show frailty signs and symptoms.

Mortality levels seemed to also be affected by the levels of mtDNA present in participants of the study. Intriguingly, when looking at the life expectancy in one of their studies, the researchers noticed an average increase of 2.1 years of life in individuals with the highest mtDNA levels, compared to those with the lowest mtDNA levels in their blood. By collecting data from both studies, it became apparent that the participants that had the lowest mtDNA levels within the population studied, were 47% more likely to die during the study period. Even more interesting was the fact that the researchers observed a higher mtDNA copy number in women of all subgroups, providing a possible factor as to why the life-expectancy for women is higher than that for men.

 

Can mtDNA levels be used as a biomarker for frailty and mortality?

According to the authors of this study, tests detecting mtDNA levels could potentially be used to predict the risk of frailty in individuals 10-15 years before symptoms actually start showing up. This could be advantageuous, because it would allow individuals to be prepared and take the appropriate steps in order to prevent or slow down this process by exercise, a healthier lifestyle, or other interventions. One of these interventions could be the administration of drugs that would increase the number of mitochondria and thus increase mtDNA copy numbers and potentially reduce the risk of frailty and mortality.

 

References:

Journal of Molecular Medicine, 2014; DOI: 10.1007/s00109-014-1233-3

Nature. 2004 May 27;429(6990):417-23.

http://www.hopkinsmedicine.org

Image copyright: Dlumen/Thinkstock

Article last time updated on 22.12.2014.

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