Researchers at the Skolkovo Institute of Science and Technology have identified a protective role for the nuclear enzyme sirtuin-6 in safeguarding DNA integrity, regulating fat and glucose metabolism, and supporting a range of crucial cellular processes that keep energy production running. This work highlights how the absence of sirtuin-6 disrupts cellular functions and can ripple through the body’s metabolic and genetic systems. The findings were shared with science audiences through a report supported by a national research funding body, underscoring the importance of sustained public investment in foundational biology.
The study positions sirtuin-6 as a central regulator of mitochondria, the tiny energy factories inside cells, with particularly important implications for brain health. When mitochondrial activity falters, neurons lose energy efficiency, which can set the stage for neurodegenerative diseases such as Alzheimer’s and Parkinson’s. The researchers’ observations suggest that maintaining adequate levels of sirtuin-6 in brain tissue could be a key factor in delaying or mitigating these conditions, especially in aging populations where mitochondrial dynamics begin to shift and DNA packaging within the nucleus becomes more prone to dysregulation.
Project leadership described a plausible mechanism: a decrease in sirtuin-6 within aging brain tissue may directly influence how DNA is packaged and unwound, altering gene expression in ways that contribute to neurodegeneration. The lead investigators hypothesize that sirtuin-6 helps regulate the removal or repositioning of certain atomic groups from DNA packaging proteins, thereby controlling how tightly DNA is wound and how accessible genes remain for transcription. Ongoing work aims to test this idea further, with a focus on how these changes affect neuronal resilience and metabolic signaling in the brain, and what that might mean for targeting age-related brain diseases in the future. Researchers emphasize that this line of inquiry could reveal new angles for interventions that support genome stability and mitochondrial health simultaneously, potentially slowing disease progression in vulnerable populations.
In their experimental model, the team reduced sirtuin-6 levels in mice to observe downstream effects. They extracted RNA from brain tissue to map which genes were being actively transcribed in neurons and paired these data with measurements of cellular metabolites tied to mitochondrial activity. The results indicated that sirtuin-6 deficiency produced widespread gene expression changes, impacting roughly 3,000 genes with a strong enrichment for those associated with mitochondrial function and energy metabolism. A particularly striking finding was a direct link between reduced sirtuin-6 and diminished mitochondrial integrity: in animals with lowered sirtuin-6, protein levels associated with mitochondria dropped by about 20 percent, and this decline correlated with a reduced mitochondrial population in brain cells. This pattern provides a tangible connection between nuclear regulation by sirtuin-6 and the health of the cell’s energy hubs, suggesting that sirtuin-6 acts as a bridge between genome organization and metabolic capacity within the brain. The implications extend beyond basic biology, hinting at therapeutic strategies that preserve mitochondrial performance and DNA regulation to support cognitive function during aging. The research team notes that while these findings come from animal models, they point to conserved mechanisms that could inform human health and disease management as the science advances. Citation: Russian Science Foundation.