Highlights: 

  • For every two additional mitochondrial DNA insertions, there was a 10-year reduction in life. 
  • Scientists are still trying to determine how to stop mitochondrial DNA insertions. 

Scientists from Columbia University, University of Michigan, and Rush University have discovered that individuals with no cognitive impairment (NCI) are more likely to die earlier if they have more mitochondrial DNA insertions called nuclear mitochondrial segments, or Numts. 


(Zhou et al., 2024) Association Between Age of Death and Numt Count. A higher Numt count in the dorsolateral prefrontal cortex (DLPFC) correlates with earlier age at death in individuals with no cognitive impairment (NCI).

For analysis, the researchers used post-mortem brain samples from the dorsolateral prefrontal cortex (DLPFC). The DLPFC is critically involved in cognitive control, particularly in overriding emotional biases and making complex social decisions by balancing emotional and deliberative processes, according to the Encyclopedia of Neuroscience. 

The brain samples were divided by whether the individual who donated the sample had no cognitive impairment (NCI), mild cognitive impairment (MCI), or Alzheimer’s dementia (AD). For the NCI individuals, every increase in two insertions was associated with a 10-year decrease in life. MCI individuals showed a similar but weaker association and AD individuals did not display a significant association. 

“These results indicate that Numts are negatively associated with age at death in certain brain regions of non-AD individuals, suggesting the possibility that brain [Numts] are deleterious…,” the authors say. 

Can Numts Be Stopped? 

It is thought that, millions of years ago, the ancestor of mitochondria (bacterial cells) merged with other cells (either bacterial or archaeon cells) to become eukaryotic cells — the type of cells that all animals, plants, and fungi are made. Eukaryotic cells harbor a nucleus, which contains linear DNA strands while mitochondria contain small circles of DNA. Studies have shown that factors such as psychological stress can trigger the release of mitochondrial circular DNA from mitochondria. The mitochondrial DNA can then travel to the nucleus and integrate with eukaryotic DNA. These insertions are called Numts. 

The researchers tested whether a stress hormone-mimicking drug could increase the rate of Numts in human skin cells. They also tested whether impairing mitochondrial function could increase the rate of mitochondrial DNA insertions. However, they found no significant increase in Numts in response to either environmental agent. Thus, more studies will be needed to determine which factors contribute to higher Numt rates, with the possibility of stopping them. 

Notably, some studies have shown that ionizing radiation or mitochondrial oxidative stress can lead to higher rates of Numts. Ionizing radiation is high-frequency energy that can knock electrons off atoms, increasing the risk of cancer. Ionizing radiation occurs naturally, such as from cosmic rays, but uranium and medical devices such as x-rays also emit ionizing radiation. Mitochondrial oxidative stress occurs when mitochondria are unhealthy and begin producing excessive levels of reactive oxygen species.

Interestingly, the NAD+ precursor NMN has been shown to counteract the harmful effects of both ionizing radiation and oxidative stress in animal models. Other NAD+ precursors, as well as numerous anti-aging compounds have also been shown to mitigate the effects of ionizing radiation and oxidative stress. However, studies are needed to determine if any compounds can alleviate the occurrence of Numts.