The hundreds of mitochondria present in every cell in the body undertake the essential duty of producing chemical energy store molecules, adenosine triphosphate (ATP), used to power the cell. With age, mitochondria become less efficient and more damaged, generating oxidative stress and triggering inflammation while producing less ATP than is optimal. This is thought to be a major contribution to degenerative aging, though as for all contributions to aging, it requires a highly targeted way to improve mitochondrial function in order to determine just how important it is. That highly targeted therapy doesn't yet exist in a useful form. The most plausible near future candidate is transplantation of young, functional mitochondria.
Mitochondria are descended from ancient bacteria that became symbiotic with early cells. As such, they retain a small remnant circular genome, the mitochondrial DNA. In today's open access paper, researchers note that while the mitochondrial transcription machinery producing proteins from DNA sequences is different from that of the nucleus, mitochondrial DNA is still subject to epigenetic marks that can change protein output. Epigenetic patterns on the genome are known to change with age, producing changes in protein levels that are some mix of harmful and adaptive. It is reasonable to think that epigenetic regulation of protein production can be just as involved in age-related declines in the mitochondria as it is in the nucleus.
Mitochondria are cellular organelles which generate adenosine triphosphate (ATP) molecules for the maintenance of cellular energy through oxidative phosphorylation. They also regulate a variety of cellular processes including apoptosis and metabolism. Of interest, the inner part of mitochondria - the mitochondrial matrix - contains a circular molecule of DNA (mtDNA) characterised by its own transcriptional machinery. As with nuclear DNA, mtDNA may also undergo nucleotide mutations that have been shown to be responsible for mitochondrial dysfunction.
During physiological aging, the mitochondrial membrane potential declines and associates with enhanced mitophagy to avoid the accumulation of damaged organelles. Moreover, if the dysfunctional mitochondria are not properly cleared, this could lead to cellular dysfunction and subsequent development of several comorbidities such as cardiovascular diseases (CVDs), diabetes, respiratory diseases, as well as inflammatory disorders and psychiatric diseases.
As reported for genomic DNA, mtDNA is also amenable to chemical modifications, namely DNA methylation. Changes in mtDNA methylation have shown to be associated with altered transcriptional programs and mitochondrial dysfunction during aging. In addition, other epigenetic signals have been observed in mitochondria, in particular the interaction between mtDNA methylation and non-coding RNAs. Mitoepigenetic modifications are also involved in the pathogenesis of CVDs where oxygen chain disruption, mitochondrial fission, and reactive oxygen species (ROS) formation alter cardiac energy metabolism leading to hypertrophy, hypertension, heart failure, and ischemia/reperfusion injury.
In the present review, we summarize current evidence on the growing importance of epigenetic changes as modulator of mitochondrial function in aging. A better understanding of the mitochondrial epigenetic landscape may pave the way for personalized therapies to prevent age-related diseases.