The power plants of the cell are, of course, the mitochondria. Every cell has a herd of hundreds of mitochondria roaming its cytoplasm, working to generate ever more copies of the chemical energy store molecule adenosine triphosphate that is used power cellular processes. Mitochondria are the distant descendants of ancient symbiotic bacteria. Like bacteria they replicate by division, but also tend to fuse together and promiscuously pass around component parts. Since the original symbiosis, mitochondria have evolved into component parts of the cell. They have their own remnant DNA, but much of the original genome has migrated into the cell nucleus over evolutionary time. Further, mitochondria are monitored and recycled when worn or damaged by the cell's autophagic mechanisms, a constant process of quality control.

Mitochondrial function declines with age. In a minority of cells, mitochondrial DNA becomes damaged in ways that allow mutant mitochondria to outcompete their functional counterparts in the herd. The cell becomes pathological, exporting harmful oxidative molecules into the surrounding tissue. This contributes to conditions such as atherosclerosis via the creation of oxidized lipids that cause macrophages to become harmful, inflammatory foam cells. In the majority of cells, mitochondria undergo a form of general malaise, becoming structurally altered and less effective in their primary role of providing energy for the cell. This may be due to a failure of quality control mechanisms, which in turn may be due to declining mitochondrial fission, but the deeper roots of these issues are unclear.

It is generally acknowledged in the research community that at least slowing and preferably turning back the course of mitochondrial dysfunction in aging is a good idea. Mitochondrial dysfunction is quite clearly implicated in many age-related diseases, particularly neurodegenerative conditions. It may underlie more subtle and pervasive manifestations of aging such as declining stem cell function that leads to reduced tissue maintenance throughout the body, as well as the many downstream issues resulting from that. I have to say that, despite this consensus, all too little of the research community is working on means of addressing mitochondrial aging that have the potential for true rejuvenation of function.

Outside of the SENS rejuvenation research programs, the mainstream of the scientific community looks toward calorie restriction mimetics and other means of tinkering with mitochondrial function without addressing the root causes of decline. Increasing the amount of NAD+ in circulation in cells, for example, is presently popular. This will produce benefits in older individuals, and the initial trials seem promising in that respect, but it doesn't solve the underlying problems. Thus this approach cannot achieve more than modest improvements in health and longevity, as those underlying problems remain, to gnaw away at the function of cells and tissues in myriad ways. The open access paper here is an example of this sort of focus, in that it does not look beyond ways to alter mitochondrial metabolism, perhaps making mitochondria a little more active or a little more resilient in the face of underlying damage. We can and must do better than this.

Negative Conditioning of Mitochondrial Dysfunction in Age-related Neurodegenerative Diseases