Reacción a "Mitochondrial DNA mutations in oocytes do not increase with age"

Mitochondria, known as the "powerhouses" of the cell, play an essential role in cellular health. Mutations in their DNA (mitochondrial DNA or mtDNA) have been associated with various diseases and have been widely studied in the context of female fertility due to their influence on oocyte quality. 

Over time, human cells accumulate somatic mutations, and mitochondria, due to their nature, are particularly susceptible. This gives rise to a phenomenon known as heteroplasmy, where multiple variants of mtDNA coexist within the same cell.  

This recent study led by Arbeithuber and collaborators analyzed these mutations using individual oocytes and somatic samples (such as blood and saliva) from the same women at different stages of their lives. To do this, they employed an innovative double-sequencing technique, which for the first time allowed direct observation of mutations in oocytes not selected through the fertilization process. 

Thanks to this methodology, the researchers were able to distinguish between: 

• De novo somatic mutations, 

• De novo mutations in the germline, and 

• Mutations that were already present and segregated within the germline. 

The main conclusion of the study is clear: mitochondrial mutations increase with age in somatic tissues but not in oocytes. This suggests a preservation or selection mechanism in the female germline that limits the accumulation of these mutations over time. 

However, other studies have shown an increase in heteroplasmy detection with an individual's age, a phenomenon attributed to processes like genetic drift. For example, the study led by Kuiper et al. analyzed more than a thousand individuals and observed a longitudinal increase in the proportion of deleterious mtDNA variants with age. 

Moreover, in previous research using mouse models, Arbeithuber and his team had already documented an increase in de novo mutations in both oocytes and somatic tissues with aging. 

However, their most recent findings in humans, published as a preprint on bioRxiv in December 2024, confirm that while there is frequency-dependent selection in mitochondrial mutations, their accumulation is not associated with age in human oocytes. 

These types of studies deepen our understanding of how mitochondrial genetic integrity is maintained in human reproduction and open new lines of research on fertility, aging, and mitochondrial medicine.