Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

We all accumulate mutations within our mitochondrial DNA (mtDNA)genome which encodes proteins necessary for our cellular energy production. The more mutations we accumulate, the less we can produce energy, the less we can maintain the health of our tissues. This damagingof the mitochondrial is believed to be one of the main reasons behind aging and age-related diseases. mtDNA mutations can be inherited or caused by inflammation and oxidative stress. However, certain drugs such as the ones used to treat HIV are believed to also induce mtDNA mutations. Evidence is accumulating that HIV-infected people age faster than non-infected people. They have diseases normally seen in older people earlier in life. It is unclear whether this is because of their HIV infection(which can cause chronic inflammation) or because of the side effects of the antiretroviral drugs they take to treat their disease. It is technically challenging to study mtDNA mutations because there are hundreds of copies of mtDNA in each cell. We have developed a deep sequencing-based methodology to detect low frequency mtDNA mutations and distinguish them from background PCR and sequencing errors. We will use a cell culture model to determine whether commonly used HIV drugs can indeed induce mtDNA mutations. We will also test samples collected from HIV+ and HIV- individuals, young and old, treated with antiretroviral or not, to investigate the relationship between mitochondrial aging, biological aging, HIV infection and exposure to HIV therapy. It is important to figure out what may accelerate aging in HIV+ individuals: the virus or the medications? It may affect how we treat HIV+ people. This research will provide tools that can be used to study mitochondrial aging in any setting or disease.