Mitochondrial DNA fragments integrate into the nuclear genome (Numts), particularly in brain tissue, increasing with age and correlating with earlier mortality. In cultured fibroblasts, new insertions appear every 13 days, accelerating under stress and mitochondrial dysfunction, suggesting potential implications for ageing and longevity.
August 2024 – PLOS Biology
Key takeaways
- Mitochondrial DNA integrates into the nuclear genome as we age: Over time, fragments of mitochondrial DNA (mtDNA) naturally incorporate into the nuclear genome, a process called numtogenesis. This occurs more frequently in post-mitotic tissues like the brain, where cells do not replicate as often, suggesting these changes accumulate progressively throughout life
- Higher mtDNA integration correlates with earlier mortality: The accumulation of nuclear mitochondrial DNA insertions in specific brain regions, such as the prefrontal cortex, is linked to reduced lifespan. Individuals with more of these insertions tend to experience earlier death, indicating a potential marker or driver of cellular ageing and longevity
- DNA insertions accumulate steadily in fibroblasts: Human fibroblasts (skin-derived cells) accumulate one new mtDNA insertion approximately every 13 days when cultured under normal conditions. This shows that mtDNA integration is a continuous process, even in cells with low division rates, suggesting it may contribute to cellular ageing over time
- Cellular stress and mitochondrial dysfunction accelerate DNA integration: Under conditions of mitochondrial stress, such as impaired oxidative phosphorylation or chronic exposure to stress-mimicking hormones, the rate of mtDNA integration increases. In particular, cells with mitochondrial instability, like those from patients with SURF1 mutations, accumulate DNA fragments almost five times faster, linking mitochondrial health to ageing processes
Read the article at: Zhou, Weichen, et al. “Somatic Nuclear Mitochondrial DNA Insertions Are Prevalent in the Human Brain and Accumulate Over Time in Fibroblasts.” PLOS Biology, vol. 22, no. 8, 2024, https://doi.org/10.1371/journal.pbio.3002723.