Mitochondrial DNA Somatic Mutation Burden and Heteroplasmy Are Associated with Chronological Age, Smoking, and HIV Infection
This week we profile a recent publication in Aging Cell from Adam Ziada (pictured, back row,
third from left) in the laboratory of Dr. Hélène Côté (back row, second from left) at UBC.
Can you provide a brief overview of your lab’s current research focus?
The Côté lab studies HIV and antiretroviral therapy, as well as the potentially harmful effects that either HIV or antiretroviral therapy can have on exposed individuals. While antiretroviral therapy has significantly reduced the mortality of individuals living with HIV, many appear to experience accelerated aging. These individuals tend to develop age-related diseases a decade or so earlier than the general population. Research in our lab aims to better understand the mechanism behind this, as well as separate the effects of the virus and the medications by studying markers of cellular and mitochondrial aging.
What is the significance of the findings in this publication?
Our paper implies that not all individuals living with HIV experience accelerated aging. It is those with a history of high levels of HIV replication, and hence greater immune activation, who show the greatest evidence of mitochondrial aging. In these individuals, the constant exposure to HIV and the immune system’s attempts to control the virus may lead to collateral cellular damage over time and drive accelerated aging. These results highlight the importance of treating people as early and consistently as possible, minimizing their exposure to replicating HIV.
We further show that people who smoke tobacco also accelerate their mitochondrial aging, and the effect appears to be as important, if not more important, than the effect of HIV. This agrees with the common understanding that smoking can lead to accelerated aging and further highlights the importance of smoking cessation.
What are the next steps for this research?
Our next steps will be to explore the effects of interruptions in HIV therapy. Lifelong HIV treatment has side effects, and access to treatment can be inconsistent in some settings. Therefore, for a variety of reasons, it is not uncommon that people temporarily stop treatment at least once, a subset of whom may experience multiple interruptions in their life. Interruptions lasting more than a few weeks would trigger a rebound of the virus each time, leading to repeated exposures of both replicating HIV and constant immune activation. We hypothesize that HIV therapy interruptions may be a driver of accelerated aging in this population.
This work was funded by:
Canadian Institutes of Health Research and National Institutes of Health