Our cells contain two types of DNA: most is found in the nucleus (nuclear DNA), but a small portion is found in structures called mitochondria, which are responsible for producing energy. Occasionally, mitochondrial DNA (mtDNA) can move into the nuclear DNA. These are referred to as nuclear mitochondrial DNA insertions, or Numts. Those Numts can build up in the human brain as we age and are associated with shorter lifespans, according to a recent study published by Weichen Zhou and his team of researchers.
The Link Between Mitochondrial DNA and Aging
The study looked at the presence of Numts in 1,187 samples of human brain and blood tissue. The brain had 10 times more Numts than blood cells. The researchers found that the numbers of Numts increase throughout a person’s life, especially in areas of the brain that do not replace cells frequently, like the dorsolateral prefrontal cortex (DLPFC). The DLPFC is important for thinking and decision-making.
The researchers found that those who had died at an earlier age and were not cognitively impaired carried more Numts. This means that as more Numts appear, it may be connected to earlier death, showing a possible link between these DNA changes and lifespan.
How Do Numts Accumulate?
The scientists used lab cultures of skin cells (fibroblasts) in a test tube to see how Numts arise over generations. Over the time, they followed these cells for accumulation of Numts. In the control human cells, Numts appeared at a slightly slower pace, about one new insertion in 13 days.
Other cells the researchers observed came from patients who had Leigh syndrome, a genetic condition that affects the ability of cells to make energy. The cells with deficient energy production accrued Numts at a faster rate suggesting that when cells have trouble producing energy, Numts appear more quickly.
The Role of Stress in Numt Accumulation
The researchers also investigated how stress may speed up the creation of Numts. Exposing cells to stress-like conditions with glucocorticoids (experimental chronic stress) or mitochondrial function disruption treatment led to faster Numt accumulation. Additionally, cells with mitochondrial dysfunction, such as those from patients with Leigh syndrome, accumulated Numts nearly five times faster. This indicates that both environmental stress and genetic factors that affect mitochondria may speed up the numtogenesis process, potentially contributing to faster aging.
What Does This Mean for Aging?
The accumulation of Numts in the brain might have something to do with aging and premature death. Higher levels of Numts in the brain were associated with mortality occurring at an earlier age, not just in individuals who died with Alzheimer’s but also those who passed away with no evidence of cognitive pathology. But just why Numts might be linked to a shorter life remains largely an enigma. They could disrupt the normal functioning of cells in ways that make the brain and body age faster.
The study finds that so-called Numts – minuscule pieces of mitochondrial DNA which slip into the nuclear genome – build up in the human brain as we age. This accumulation could be connected to it ageing and have a shorter life span. By understanding how these DNA changes happen and affect the brain, scientists hope to learn more about the aging process and find ways to improve health as we grow older.
Source Study: https://www.biorxiv.org/content/10.1101/2023.02.03.527065v3