Researchers have uncovered a crucial molecular process that could be contributing to chronic inflammation as we age. This discovery, if accurately targeted, might pave the way for strategies to maintain health in later years. The study focuses on the unique strands of DNA within mitochondria, known as the cell’s powerhouses. By ejecting their ‘mtDNA’ into the surrounding cytoplasm, mitochondria can trigger inflammation, a process that has remained largely enigmatic until now.
This groundbreaking research was spearheaded by a team from the Max Planck Institute for Biology of Ageing in Germany. They analyzed tissue samples from humans and test animals, including mice genetically engineered to model aging and disease. Their findings could have significant implications for understanding and potentially mitigating age-related health issues.
Understanding the Molecular Mechanism
The research reveals that when mitochondrial DNA (mtDNA) lacks sufficient DNA building blocks, known as deoxyribonucleotides, it mistakenly incorporates RNA building blocks, or ribonucleotides, instead. This error leads to instability in the mtDNA, causing it to be expelled from the mitochondria. This process, as explained by molecular biologist Thomas Langer from the Max Planck Institute, elucidates how metabolic disturbances can lead to inflammation in aging cells and tissues, opening new avenues for intervention.
Previous studies have demonstrated that deoxyribonucleotides become less abundant with age, reducing the availability of genetic building blocks in older cells and senescent tissues. This latest investigation suggests that the lack of these building blocks prompts mtDNA to incorporate ribonucleotides, potentially explaining why mitochondria reject these ‘imperfect’ DNA copies.
The Impact on Aging and Health
The expulsion of flawed mtDNA is believed to be a key driver of the inflammation associated with aging, which can lead to various negative health outcomes, including certain cancers and neurodegenerative diseases like Alzheimer’s. As the researchers noted, this response, while protective against pathogens, can also promote autoimmune and inflammatory diseases, contributing to cellular senescence and aging.
“This response provides protection against pathogens but can also promote autoimmune and inflammatory diseases and contribute to senescence and aging,” the researchers stated in their published paper.
It remains uncertain how prevalent this form of inflammation is during normal aging or whether it occurs under specific conditions. However, as life expectancy increases, the biological machinery of the human body is under greater strain, accumulating stress, damage, and inflammation, which can compromise health.
Potential Interventions and Future Research
Understanding how to prevent mtDNA from making these replication errors could lead to ways of preserving cellular health in old age. Molecular biologist Dusanka Milenkovic from the Max Planck Institute notes that there is an existing therapy for certain mitochondrial diseases that involves administering DNA building blocks. However, it is still unclear if this treatment can also alleviate age-related inflammation.
“There is already a therapy for certain mitochondrial diseases that involves administering DNA building blocks,” says Milenkovic. “However, we do not yet know if it can also alleviate the inflammation that occurs more frequently with age. It would be interesting to test this.”
The discovery of this molecular mechanism offers a promising avenue for future research, with the potential to develop interventions that could significantly improve health outcomes as we age. By targeting the underlying causes of inflammation, scientists hope to mitigate the health challenges associated with aging, ultimately enhancing quality of life for older adults.
