April 27, 2016
By measuring a molecular signature of aging, researchers have found that HIV infection accelerates aging, adding an average of five years to someone's biological age. The more rapid aging is occurring in people receiving antiretroviral treatment, so that even though treatment enables them to live for many decades, they remain at higher risk of aging-related chronic disease.
Studies of people with HIV infection have noted a higher risk of diseases associated with aging, such as liver and kidney failure, cancer, and heart disease. While the observations have suggested that HIV infection causes accelerated aging, there hasn't been a biologically based marker of aging with which scientists could clarify and quantify the impact of HIV on aging.
In search of such a marker, scientists at the University of Nebraska Medical Center, led by Howard Fox, M.D., Ph.D., in collaboration with scientists at the University of California, San Diego School of Medicine, led by Trey Ideker, Ph.D., turned to epigenetics, a term for changes to DNA that affect its function without altering the sequence of bases that make up DNA. Through epigenetic processes, experience can alter the genome, silencing or activating genes.
"The medical issues in treating people with HIV have changed," says Fox. "We're no longer as worried about infections that come from being immunocompromised. Now we worry about diseases related to aging, like cardiovascular disease, neurocognitive impairment, and liver problems."
The team also found that one region of the genome was particularly rich in HIV-associated changes in methylation: this region, the human leukocyte antigen locus, encompasses genes that encode molecules that are central to immune responses. The authors suggest that epigenetic processes may contribute to the changes in regulation of this region of the genome and thus the progression, or control, of HIV.
The work provides an objective method of assessing the impact in individuals of HIV on biological age. It provides insight into the mechanisms behind the accelerated aging, and may offer a means of identifying individuals vulnerable to aging-related chronic disease, and who may benefit from more careful attention to monitoring and preventive treatments. Given epigenetic changes observed in the HLA region, it may provide clues to future approaches to controlling infection.
"Among the areas that NIH has identified as high priority for HIV research in the next three to five years are studies on the impact of HIV-associated comorbidities such as premature aging associated with long-term HIV disease and antiretroviral therapy," said NIMH's Division of AIDS Research Director Dianne M. Rausch, Ph.D. "This work is important for the insight it provides into the mechanism of HIV-associated accelerated aging and the potential it offers in terms of a biomarker for identifying individuals with HIV infection who are at greatest risk of aging-related disease as well as the development of targeted interventions."
The study is online April 21 in the journal Molecular Cell.
Gross AM et al. Methylome-wide analysis of chronic HIV infection reveals five-year increase in biological age and epigenetic targeting of HLA. Molecular Cell (2016). 2016 Apr 21;62(2):157-168. DOI: http://dx.doi.org/10.1016/j.molcel.2016.03.019.
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