Mitochondria, the power plants of the cell, have their own small genomes left over from their ancient origins as symbiotic bacteria. This mitochondrial DNA (mtDNA) becomes damaged in ways that evade cellular quality control mechanisms as a consequence of the normal operation of metabolism. Over the course of a human life span this leads to a small population of cells overtaken by dysfunctional mitochondria, emitting a flood of damaging reactive molecules into surrounding tissues. This contribution to degenerative aging could be removed entirely if we had the means to regularly replace and remove these damaged mitochondrial genomes, or alternatively to deliver an ongoing supply of mitochondrial proteins - as DNA damage is only significant because it removes or alters the blueprints required to generate specific proteins. It is the proteins that are needed for correct mitochondrial function to continue. Given a major research and development initiative working prototypes of these repair technologies are actually only a few years away, but despite a number of teams working on these approaches at a slow pace, until much more funding is devoted to this cause that few years away will continue to be the case.
Here is a recent open access review of the mechanisms by which mitochondrial DNA damage is thought to promote the development of atherosclerosis, such as - but not limited to - formation of oxidized low-density lipoprotein (LDL) molecules that aggravate cells in blood vessel walls into an ultimately harmful reaction. They draw in immune cells that try to consume and break down the LDL, but these cells can be overwhelmed to turn into foam cells or die to create a clot of debris that can grow to become a plaque. That in turn can cause a catastrophic blockage of blood flow, and death:
Atherosclerosis, by far the greatest killer in modern society, is a complex disease which can be described as an excessive fibrofatty, proliferative, inflammatory response to damage to the artery wall involving several cell types. Clinical manifestations of atherosclerosis, i.e. mainly coronary artery disease and stroke, are the leading causes of death in all economically developed countries, accounting for up to 65% of total mortality. Many factors appear to contribute to the development of atherosclerosis, [however] the precise mechanisms of atherogenesis are still unclear, even if it is well known that the deposition of intracellular lipids, mainly free and esterified cholesterol, as well as subsequent foam cell formation are the most typical features of early atherosclerotic lesion development. Modified low-density lipoprotein (LDL) is generally thought to be the source of accumulating lipids. Intracellular lipid deposition may act as a trigger mechanism for the development of advanced atherosclerotic lesions.
The mechanisms of mitochondrial genome damage in the development of chronic age-related diseases such as atherosclerosis are not well understood. There is very little data yet showing a causal relationship between mtDNA damage and atherosclerosis, although mitochondrial oxidative stress has been shown to correlate with the progression of human atherosclerosis. Mutations of the mitochondrial genome may play a pathogenic role in the formation of atherosclerotic lesions in arteries. The mitochondrial electron transport chain constantly produces superoxide radical anions, which, in the case of mitochondrial dysfunction, cause the escape of electrons that readily form hydroxyl radicals and hydrogen peroxide from superoxide. These extremely reactive oxygen species (ROS) are risk factors for atherosclerosis associated with lipid and protein oxidation in the vascular wall. ROS formation may trigger a cascade of events such as modification of LDL, inflammation, cellular apoptosis and endothelial injury.