The mitochondria are to the eukaryotic cell what the heart is to the body. Responsible for maintaining cellular energy balance, mitochondria also lie at the nexus of the signaling pathways controlling apoptosis, or programmed cell death. As a result, mitochondrial trouble - especially oxidative stress produced by metabolic defects - can wreak havoc with multiple organ systems simultaneously, blurring medical science's conventional boundaries.
"All the people under the age of 35 have nice full-length mitochondrial DNAs; all us old duffers over the age of 50 all had a different array of mitochondrial mutations," he says. In chimpanzees, which live about half as long as humans, the researchers found that the same number of mitochondrial DNA mutations accumulate in about half the time. Mitochondria in mice mutate even faster, in direct proportion to the much shorter lifespans of these animals. "So in fact there seems to be a nice correlation between accumulation of somatic mutations and aging," says Wallace.
To test this correlation, the team created transgenic mice that express the catalase enzyme in their mitochondria. Catalase breaks down the reactive species hydrogen peroxide, and the reduction in oxidative stress allows these mice to live about 20% longer than their wild-type brethren.
Besides helping to drive generalized aging, reactive oxygen species may also mediate the progression of specific diseases.
Developing the means to repair our mitochondrial DNA - or cleverly make damage to that DNA irrelevant - is clearly important. It's one of many lines of research in the fight to defeat degenerative aging, but like the others, we can clearly see the finish line from where we are now. A number of different approaches presently exist, and some, like protofection, have been demonstrated in the laboratory.
This achievement has important implications for medicine: protofection technology works in vivo, and should be capable of replacing damaged mitochondrial genomes.
What is needed, and what is lacking, is funding, support, and widespread understanding of just how close we are to real progress in the development of the first generation of working rejuvenation medicine.