As you all know by now, accumulated mitochondrial DNA (mtDNA) damage is thought to provide an important contribution to degenerative aging. The process by which the small misplaced, changed, or missing segments of DNA known as mutations create the conditions for failing organs - and ultimately death - is complex and has many steps, but it starts with changes in the operation of crucial mitochondrial machinery. You might want to look back into the Fight Aging! archives for an overview of the mitochondrial free radical theory of aging, which walks though the present understanding of this process.
I was interested to note today that there is some evidence for the existence of beneficial mutations to mitochondrial DNA that accumulate with age in at least some populations. On reflection this doesn't seem unreasonable. We know, for example, that some mitochondrial DNA haplotypes are demonstrably better than others - they are associated with people who, on average, benefit from better health and longevity. Some folk have the luck of the draw and inherit good mitochondrial machinery. But our cells are more than just the straight output of their DNA blueprints, both nuclear DNA and mitochondrial DNA, because cellular processes and mechanisms can conceivably influence the way in which those blueprints become damaged over time.
So we have this intriguing open access paper, which suggests that some human populations may have evolved to allow certain specific types of damage to readily occur in their mitochondria, because that damage changes mitochondrial operation in ways that provide benefits to survival. Devious, but then that's biology for you:
It has been recognized for a long time that age-related random damages to mtDNA and the consequent decrease in the respiratory chain capacity are among the major contributors to the aging process. ... However, in the last decade different studies highlighted specific somatic mutations in the mtDNA Control Region (CR) which can reach high levels in aged individuals. These mutations are tissue-specific and occur at mtDNA sites which are critical for replication or transcription.
Interestingly, it has been found that the CR heteroplasmic point mutations are over-represented in centenarians with respect to younger subjects in the Italian population. Data [on] twin pairs have proposed that the heteroplasmic levels of [point mutations] were genetically controlled. This hypothesis has been bolstered by analyzing centenarians' families, where we demonstrated that CR heteroplasmy in centenarians' descendants (children and nieces/nephews) are significantly higher than in age-matched controls and, moreover, they are significantly correlated in parent-offspring pairs. Thus, it has been proposed that the CR somatic point mutations may represent a remodelling mechanism which would restore the replication machinery, providing a beneficial effect on longevity.
Point mutations, you might recall, are probably not a big deal for the integrity of mitochondrial DNA insofar as aging is concerned. Researchers have demonstrated gene engineered mice packed with an outrageous level of point mutations in mitochondrial DNA, and which suffered no side effects for it. Degenerative aging is most likely advanced by other, more drastic forms of mutational damage that cut out whole sections of DNA or mash up genes in worse ways.
While this is all very fascinating, we shouldn't lose sight of the fact that the inherent quality of our mitochondrial DNA doesn't really matter. All of us lacking very bad luck make it to our thirties in a youthful state regardless of the variations in mitochondrial DNA we carry. The correct big picture view is to be thinking about ways to repair mitochondrial DNA every few decades, so as to return it to its original form before the level of mutational damage starts causing us real harm.
Given funding and motivated researchers, we stand no more than a decade or two away from the ability to replace mitochondrial DNA wholesale in all the cells of a human body. It has been five years since this was demonstrated in a mouse, but there is little work taking place on this path. Similarly, we stand only ten to twenty years from being able to import backup copies of all of the real problem genes in mitochondrial DNA into the nucleus - where they will escape mutational damage and keep the mitochondrial machinery running in tip-top condition. This has been demonstrated for one or two of the thirteen genes needed. Again, there are few research groups engaged in this work, and little funding for it.
Here, as in so many areas of engineered longevity, the science is far, far ahead of public understanding, availability of funding, and the will to get the job done.