Mitochondrial DNA Amounts Correlate with Frailty and Mortality

Researchers here find an association between the amount of mitochondrial DNA (mtDNA) in tissues and the risk of frailty and mortality. The less mitochondrial DNA you have, the worse off you are likely to be, or so it seems. It is an interesting result, though at this point we can only speculate about how this relates to the role of mitochondrial DNA damage in aging. The many processes involved in mitochondrial dynamics are collectively exceedingly complex and the amount of mitochondrial DNA in cells has no direct relationship to its quality, yet both can impact health.

[Researchers] analyzed the amount of mtDNA in blood samples collected for two large, human studies that began in the late 1980s and tracked individuals' health outcomes for 10 to 20 years. After calculating how much mtDNA each sample contained relative to the amount of nuclear DNA, the team looked at measures of frailty and health status gathered on the studies' participants over time. On average subjects who met the criteria for frailty had 9 percent less mtDNA than nonfrail participants. And, when grouped by amount of mtDNA, white participants in the bottom one-fifth of the study population were 31 percent more likely to be frail than participants in the top one-fifth. "It makes intuitive sense that decreased mtDNA is associated with bad health outcomes. As we age, our energy reserves decrease, and we become more susceptible to all kinds of health problems and disease."

The researchers also analyzed the age at which participants died. In one of the studies, high levels of mtDNA corresponded to a median of 2.1 extra years of life compared to those with the lowest levels of mtDNA. Using data from both studies, the team found that those with mtDNA levels in the bottom one-fifth of the population were 47 percent more likely to die of any cause during the study period than were those in the top one-fifth. They also found that women had an average of 21 percent more mtDNA than men. This could play a small role in why women live two to four years longer than men on average. The research team would like to take repeated blood samples from individuals over several years to learn if and by how much mtDNA levels decrease over time. What the investigators saw in the current study is that, averaged over the population, an increase of 10 years in age corresponded to 2.5 percent less mtDNA.



Is the amount of mtDNA in the tissue acting as a proxy for the number of mitochondria, or is there also significant variation in the amount of mtDNA per mitochondrion?

Posted by: Brandon Berg at December 17th, 2014 9:45 AM

It is unclear to me from the article if the mtDNA measured has been absorbed by the red blood cells, or it was just floating around between the blood cells. I am going to assume the former and guess that this shows a correlation between the mtDNA concentration in red blood cells and cell membrane permeability. And thus higher *individual* cell membrane permeability is correlated with greater longevity.

Posted by: JohnD at December 17th, 2014 1:26 PM

I wonder if SENS are getting close to allotopically expressing all 13 of the protein coding mitochondrial genes? I couldn't really tell from their last research report.

Regardless, once they do this in a mouse model, it should settle the question once and for all of how much of aging in various organs is due to mtDNA deletions.

I also kind of hope it has a effect on the aging appearance of skin, because anything that works to make people look younger has a strong economic incentive to be realized.

Posted by: Jim at December 17th, 2014 6:12 PM

@Brandon Berg: Mitochondria can absolutely have multiple copies, and there is a constant dynamic flux in copy number versus count of mitochondria. They can fuse, split, and exchange components, and do so promiscuously.

Posted by: Reason at December 17th, 2014 6:15 PM

This is a form of damage that we already know how to repair!

Pyrroloquinoline quinone, aka PQQ, is well known to increase mitochondrial DNA levels. There is very good evidence in rodents, and some evidence in human cells in vitro. Using it also seems to partially repair, prevent, or render harmless various other forms of damage such as amyloid beta or alpha synuclein.

Anything that activates SIRT1, for example Resveratrol, also seems to increase mitochondrial DNA levels.

Anything that activates AMPK, for example Metformin, Gynostemma Pentaphyllum, and Trans-Tiliroside, also seems to increase mitochondrial DNA levels, but perhaps not in all tissues.

For those who insist on not spending money on supplements, the following also appear to stimulate mitochondrial biogenesis: endurance exercise, exposure to cold, and massage therapy.

Or you can try to increase mitochondrial function without increasing mitochondrial number by using NAD+ precursors, or CoQ10, Carnitine, etc.

The Life Extension Foundation sells all this stuff. So it is a target that can be treated right now.

Or you can help fund SENS with the end of year fundraiser and get your donations doubled, which will help fund research into the transfer of mitochondrial DNA to the nucleus, preventing it from being damaged and leading to a cascade of aging effects. They are making good progress but are short on funds.

Posted by: Carl at December 18th, 2014 12:10 AM

FYI: Unlike all other common plasma and serum cells, mature red blood cells are devoid of mitochondria -- and thus powered only by non-oxidative glycolysis.
Hope that helps.

Posted by: akamai at December 27th, 2014 8:47 PM

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