The Dangers of Mitochondrial Toxicity: An Update From the 1st International Workshop on HIV & Aging

This is part of a series of articles summarizing presentations from the 1st International Workshop on HIV & Aging, which took place in Baltimore, Md., from Oct. 4 to Oct. 5, 2010. Jump to the table of contents to see the other articles in this series.

One of the best presentations of the conference was given by Douglas Wallace, Ph.D., who explained a very complex subject in a very entertaining and clear way.

He explained that the mitochondria are tiny, bacteria-like parts of our cells that produce energy (in the form of ATP). There are several types of mitochondria (each group encompasses a cluster of mutations generally found in a different world region), and those different types may help explain why some ethnic groups differ from others in the way they respond to HIV medications and their side effects. These region-specific mitochondrial differences also may explain how different races and geographical regions respond differently to diet composition and exercise. (Incidentally, the type of mitochondria we have is inherited from our mothers.)

Inherited mitochondrial mutations are known to cause several hereditary diseases. Also, mitochondria get less and less efficient at burning glucose and fatty acids for energy as we age, which leads to some health-related issues as we grow older. Medications can also damage the DNA inside the mitochondria.

We have learned in the past that the nucleoside analog class of antiretrovirals, which includes Retrovir (zidovudine, AZT) and Zerit (stavudine, d4T), cause mitochondrial toxicity that is associated with subcutaneous fat loss (lipoatrophy), muscle weakness (myopathy), and possibly neuropathy. I have seen some limited data at other conferences that other HIV medications may also have negative effects on the mitochondria, but we still do not know to what extent.

There is a perception in the HIV/AIDS research world that mitochondrial toxicity no longer exists in industrialized countries, since guidelines have long since stopped recommending Retrovir and Zerit as preferred treatments. However, HIV medications are not the only source of insult to the mitochondria. For instance, aging itself (regardless of HIV status) decreases mitochondrial DNA and function. When cells burst via apoptosis, mitochondria may be released in the blood stream, where they are perceived by the immune system to be bacteria and are attacked, which may increase immune activation.

Decreasing cell apoptosis with antioxidants or exercise may be a way to decrease this problem. However, Wallace noted that hardly any research is being done in finding ways to protect the mitochondria so that many HIV- and non-HIV-related health problems do not occur. He mentioned that the current model of treating symptoms and with more drugs is not as effective as one that would address ways to enhance and protect mitochondrial function. Hopefully, community research activists will look at these issues and help advocate for more research in this area.