DNA Methylation Reveals HIV-Infected Men Age Faster

It has been found that HIV in men results age faster compared to normal people. According to the results of a recent experiment, Trey Ideker, Chief of Medical Genetics and Professor of Medicines and Bioengineering at the University of California, San Diego, in collaboration with Howard S Fox, MD,  Professor and Executive Vice Chair of Pharmacology and Experimental Neuroscience at the University of Nebraska Medical Center in Omaha, recently found that people with HIV infections have a faster cellular aging as compared to normal people.

The scientists studied the DNA methylation pattern of HIV-infected individuals’ versus normal people and found that HIV-infected patients taking antiretroviral therapy aged faster than the normal subjects. The study, covered in The Journal of the American Medical Association (JAMA), described the role of the epigenetic clock, the role of drugs and the virus, and how the hypo-methylation of Human Leukocyte Antigen (HLA) favors the findings.

It was found that, on average, the biological age of HIV-infected patients was about 5 years ahead of their chronological age, subsequently HIV-infected patients are at a 19% increased risk of mortality. Study results also revealed that HIV-infected patients taking anti-retroviral therapy often develop age-related conditions known as cardiovascular diseases, bone fractures, hypertension and renal failure earlier than non-infected humans.

To study the DNA methylation pattern of HIV-infected patients, the scientists  collected blood samples of about 137 non-Hispanic white men aged 25-68 years infected with HIV and receiving anti-retroviral therapy. Meanwhile, the control group contained blood samples of about 44 healthy non-Hispanic white men. Researchers subsequently extracted DNA samples from the men and analyzed the genome-wide methylation patterns.

Results indicated that not all genes are on all the time. DNA methylation is an epigenetic mechanism used by the cells to control the gene expression and is commonly used to fix genes in the off position. DNA methylation occurs by adding the methyl group and is carried out by a group of enzymes called DNA methyl transferases.

“It turns out as you age, these marks on DNA change quite a bit. You can use them as a kind of clock”, says Ideker. According to Ideker, DNA methylation is similar to a molecular marker and can be used to measure the process of biological aging.

In a previous HIV in Men study in 2013, Ideker found that methylation patterns can be used to predict the chronological age within 3.9-4.9 years with an accuracy of 91%-96%.There were also a few other HIV research which found that HIV-infected patients aged 5 years earlier than their  chronological ages and had a mortality rate of 16%.

The query is what causes the aging process to move faster? Is it the anti-retroviral drug treatment or the virus itself? It is a known fact that virus are small harmful agents that attack our body’s immune system upon entering it and eventually control it. Therefore, it can be hypothesized that when the virus attacks, the body slows down its immune system, making it weaker, thereby turning our body into a platform for germs.

Similarly, in the case of therapy, although HIV treatments have improved over time, the side effects of these HIV therapies, ranging from mild to severe, still appear in some patients. Predictions can be made that these time-consuming and painful treatments eventually make the body weaker and vulnerable to germ attacks.

 Surprisingly, during the study it was discovered that the average rate of aging among infected patients was same, disregarding the duration of infection. Ideker states that our molecular assay are incapable to differentiate in the age acceleration rate between people infected recently and those who have been infected for a longer period of time. The twist is that Human Leukocytes Antigens (HLA) were also found to be hypo-methylated which authenticated the findings.

Human leukocyte genes are coded for a complex of cell-surface proteins responsible for the regulation of the immune systems in humans. Scientists later discovered that the human leukocyte antigen (HLA) hypo methylation is associated with the HIV status and may also have a link to the infection and inflammation. Further explained was that the inflammation might be linked with the early onset of non-AIDS- related diseases such as cardiovascular and neurocognitive diseases in HIV patients, which clearly favors the findings of the study.

These findings are a progressive step towards new interventions  in the field of adjuvant pharmacology to invent such drugs that could actually delay the onset of age-related diseases in HIV- infected patients such as statins.

A study is currently in progress to check if statins can be properly utilized in the reduction of cardiovascular diseases among HIV-infected patients. Hype-methylation of HLA also shows that targeting the hypo-methylation of HLA would be a valid drug target too.

Leave A Reply

Your email address will not be published.