Stress-Induced Mitochondrial Dysfunction: A New Perspective on Brain Health and Aging

 

Mitochondria, the "powerhouses" of our cells, have always held a unique position in biology due to their distinct origin. These days, the production of the energy required for our cells to function depends on mitochondria. But new studies have revealed an unexpected aspect of their behavior mitochondria might be much more than just basic energy sources. They have the ability to behave like viruses by inserting their DNA into the nucleus of the cell in a way that may interfere with regular biological processes. Nuclear-mitochondrial segments (NUMTs) are terms given to these DNA insertions that are now associated with aging, brain deterioration, and even shorter lifespans.

Mitochondria’s Viral-Like DNA Invasion

Mitochondria possess unique DNA that is inherited from their bacterial progenitors, in contrast to other organelles. Our cells' mitochondrial DNA (mtDNA) has evolved through a distinct process than the nuclear DNA in those cells. Small pieces of this mtDNA, however, have the ability to break free from the mitochondria and merge with the nuclear genome of the cell over time. This action is similar to that of retroviruses, which replicate by introducing their own genetic material into the host's DNA. Although these insertions in the mitochondria are not intended for reproduction, they may nonetheless result in genetic instability.

Throughout our lives, NUMTs have the ability to ingrain themselves into chromosomes, potentially disrupting the regular operation of genes and systems involved in cellular repair. Although this viral-like behaviour was previously thought to be uncommon, recent research indicates that it occurs more frequently than before.

Mitochondrial DNA Insertions in the Brain: What It Means for Health

The brain depends substantially on optimal mitochondrial activity because it is an organ that uses a lot of energy. Nonetheless, the research discovered that brain cells, particularly those in the prefrontal cortex, have a high frequency of mitochondrial DNA insertions. Because decision-making, memory, and personality all depend on this area of the brain, any interruption in its normal functioning is especially fatal.

After examining the brain tissue of more than a thousand elderly adults, researchers found that those with more NUMTs in their prefrontal cortex typically passed away sooner than those with fewer insertions. Given the correlation shown between NUMTs and lifetime, it is plausible that mitochondrial DNA insertions may have detrimental effects on brain function, possibly exacerbating neurodegenerative illnesses, cognitive decline, or even aging in general. Since neurons, the brain's main cells, are difficult to repair, any harm brought on by NUMTs is likely to compound over time and raise the possibility of functional deterioration.

The Impact of Stress on NUMT Accumulation and its mitigation

Stress contributes to the build-up of nuclear-mitochondrial segments (NUMTs), which is one of the most fascinating discoveries of recent studies. Stressors like poor diet, bad lifestyle choices, and environmental conditions can trigger mitochondrial malfunction, which can dramatically quicken the rate at which NUMTs build up in cells. Researchers found that strained mitochondria induced NUMTs to generate four to five times faster than in healthy cells when using human skin cells in lab studies. This implies that our cells are more vulnerable to the deleterious consequences of mitochondrial DNA insertions when they are under prolonged stress.

More NUMTs tend to accumulate in the brain than in other tissues, which may account for the connection between age-related cognitive decline or neurological illnesses like Alzheimer's disease and stress-related mitochondrial malfunction. The brain is particularly vulnerable to alterations in metabolism.

Although NUMT integration is an inevitable aspect of growing older, there are things we may do to lessen its effects. It is important to maintain the health of the mitochondria, and cellular stress can be decreased to do this. Mitochondrial function can be protected by behaviors such as eating a balanced diet high in antioxidants, exercising frequently, and controlling psychological stress. Antioxidant-rich foods including leafy greens, berries, and almonds can lessen oxidative stress, which is a significant cause of mitochondrial dysfunction.

Furthermore, it is possible that future treatments will be able to prevent NUMT production or reverse the harm that these insertions produce. Drugs that target mitochondrial health are already being investigated by scientists; if successful, these treatments may stop mitochondrial DNA from acting like a virus, thereby preserving brain function and general health as we age.

REFERENCE:

1.     Weichen Zhou, Kalpita R. Karan, Wenjin Gu, Hans-Ulrich Klein, Gabriel Sturm, Philip L. De Jager, David A. Bennett, Michio Hirano, Martin Picard, Ryan E. Mills. Somatic nuclear mitochondrial DNA insertions are prevalent in the human brain and accumulate over time in fibroblasts. PLOS Biology, 2024; 22 (8): e3002723 DOI: 10.1371/journal.pbio.3002723

2.     IMAGE SOURCE- https://www.veriheal.com/conditions/mitochondrial-disease/