Research Roundup: Mitochondrial DNA, d-Ribose for Heart Failure
Two quick and interesting studies related to mitochondrial function.
The “Longevity Research Roundup” is a feature for paid subscribers of Longevity Lifehacks. Every week or two, I will bring you a quick summary of new research studies that I think are important — and actionable — in the fields of longevity, lifespan, or healthspan.
Study #1: Ribonucleotide incorporation into mitochondrial DNA drives inflammation Nature (2025), Bahat, et al.
This new study gets to the heart of aging in a way that I am still trying to wrap my head around.
Mitochondria have their own small set of DNA that codes for about 37 proteins that are essential for mitochondrial function. Each cell in the body has mitochondria producing ATP for energy, with most cell types having hundreds of copies of mitochondria per cell. They are a dynamic organelle, often fusing, dividing, replicating, changing shape, and forming networks. Lots of replication means that the mitochondrial DNA gets replicated constantly.
Mitochondrial DNA (mtDNA) that is released into the cytosol of the cell is a signal, a sign of distress that causes an inflammatory response.
In this new study, the researchers showed that the reason that mtDNA is released into the cytosol much more often in aging (thus triggering inflammation and cellular senescence) is due to RNA nucleotides being incorporated into the mtDNA instead of DNA. The researchers found that when mtDNA can’t find enough deoxyribonucleotides, the DNA building blocks needed for replication, it picks up RNA building blocks, called ribonucleotides. Incorporating the RNA ribonucleotides causes the mtDNA to be unstable, resulting in it often being rejected into the cytosol. This signals for inflammatory cytokines and can cause cellular senescence.
Prior research showed that as we age, deoxyribonucleotides are less abundant. So the lack of DNA building blocks resulting in RNA incorporation into mtDNA drives cellular senescence and inflammaging.
