Acceleration of epigenetic clock
These studies establish a scenario using methylation patterns to investigate whether people with HIV advance their organ age faster than uninfected, said Ideker, who for the new study collaborated with Howard S. Fox, MD, PhD, professor and vice - executive chair of pharmacology and experimental neuroscience at the University of Nebraska Medical Center in Omaha.
His research team took blood samples from a total of 137 non-Hispanic white men aged 25 to 68 years who were infected with HIV and taking antiretroviral therapy. In addition, they took blood samples from 44 healthy non-Hispanic men, white and non-HIV infected individuals. The research team isolated the DNA from these samples and analyzed all methylation patterns of the genome using molecular techniques.
The results demonstrated that the biological age of HIV-infected men on antiretroviral therapy is on average about 5 years ahead of their chronological age, resulting in 19% increased risk of mortality. In contrast, the biological and chronological ages of their healthy counterparts were closely aligned. All but 15 of HIV-infected men had some degree of advanced age, Ideker said.
"The beauty of this bookmark is that it is very fast, quantitative and conclusive," said Ideker.
Methylation data was what researchers and clinicians needed to validate the anecdotal observations that people with HIV age faster, Fox noted.
"The epigenetic clock of methylone predicts whether increased mortality or morbidity is accelerated and [our study] actually showed that this clock was advanced in patients with HIV," Fox said.
In addition to accelerated aging in HIV-positive individuals, Ideker and Fox team also found that the average rate of acceleration of age was the same regardless of how long the person had been infected with HIV, which was unexpected.
"I'm not entirely sure how to interpret this result," said Ideker, noting that perhaps the rate of advanced age is constant over time or, alternatively, trials do not have the power to detect subtle differences in age acceleration between those who were recently infected and those who had been infected for many years.
Viruses or drugs?
What is not yet clear is whether this accelerated aging is due to the virus's own or long-term effect of antiretroviral therapy. Chronic inflammation resulting from viral infection may be leading to early onset of age-related morbidities in HIV-positive patients, noted Larry Corey, MD, Professor of Medicine at the University of Washington and past president of the Fred Hutchinson Cancer Research Center. Seattle. Corey directed the AIDS Clinical Trial Group in 1987.
"We know clinically that HIV causes a continuous inflammatory response," Corey said.
While it is possible that antiretroviral drugs may play a role in accelerated aging, Corey said that it is unlikely because this accelerated aging appears to occur among HIV patients, no matter which combination of antiretroviral drugs they are using. Instead, he suspects that reactivation of latent HIV reservoirs may contribute to the process.
In any case, it is a moot point because HIV is deadly if the patient does not take antiretroviral medication, Fox pointed out.
Another question that remains is what accelerated aging rate occurs among HIV-infected women and people of different racial groups, noted Carl Dieffenbach, PhD, director of the AIDS division of the National Institute of Allergy and Infectious Diseases, who was not involved with study.
"The aging of the woman is a bit more complicated with the effect of estrogen," said Dieffenbach.
The study is solid and well done and points to HIV research for 'very interesting directions', commented Dieffenbach.
One finding with key clinical implications, Dieffenbach notes, is that human leukocyte antigen (HLA), genes that regulate the acquired immune response, have been hypomethylated in HIV-infected men.
"The direction this points us is that other diseases are associated with [HLA] hypomethylation?" Dieffenbach commented.
Researchers also found that hypomethylation is associated with HIV status and may be related to infection control and subsequent inflammation. The inflammation
caused by HIV infection, in turn, may be associated with the early onset of non-AIDS-related diseases such as cardiovascular disease and cognitive impairment in HIV-positive patients, Fox explained. He noted that this finding supports his overall conclusion that advanced biological aging predicts increased morbidity and mortality.
Another interesting question that the study raises, said Dieffenbach, is whether accelerated aging can be attenuated in people with HIV infection or if it is permanent.
"The virus, after taking the human body, establishes a path from which it can not recover or" change course "?" Dieffenbach said. "Even as the drugs got better and better, people with HIV infection show a deficit of 5 to 7 years in the expectation and quality of life."
Slowing the clock
Along these lines, the results of this study may encourage ongoing lifestyle research and adjunctive pharmacological interventions, which could potentially delay the onset of age-related illness in HIV-positive individuals, Ideker noted. For example, a study currently underway is examining whether statins can reduce the risk of cardiovascular disease among HIV-positive adult patients aged 40 to 75 years who are having antiretroviral therapy without a history of heart disease (http://www.reprievetrial.org).
Editor's note: I showed the article about it to my doctor and she found reasons to prescribe statins me. "
The National Institute on Aging has called attention to the possible link between inflammation and age-related illness in people with HIV and is supporting studies of anti-inflammatory interventions such as aspirin and vitamin D (http://1.usa.gov/1SRXacL).
The study by Ideker and Foxsugere suggests that HLA genes may be a potential target of the drug to prevent the early onset of age-related diseases linked to chronic inflammation, Dieffenbach said.
"The hypomethylation of HLA locus is telling us something about how HIV changes the immune response, tilting the balance in favor of the virus", Dieffenbach said. “ Focusing on hypomethylation leading to a better immunity to HIV disease, as well as chronic diseases [such as heart disease] is a valuable drug target. ""As a family history of a certain disease, seropositivity of a patient should be seen as a major risk factor for other diseases, Fox said, requiring that doctors have "increased vigilance, increased prevention, and increased screening [for morbidities age-related]. "
Julie A. Jacob, MA
Translated by Claudio Souza Original in Men With HIV Age FasterAccording to DNA Methylation Study
Review Bob Volpe (Tantum Nominum Nulum par Elogium)
(*) Translator's Note: Early in the reading bumped into the term "Methylation". I concluded that without clarifying this point, even if pifiamente, I would be going against the tide and found the following : Methylation is the term used in chemical sciences to name the bond or substitution of a methyl group over several substrates. The term is commonly used in chemistry, biochemistry, science of alone and in the biological sciences.
In biochemistry, methylation refers more specifically to the substitution of an atom of hydrogen by the methyl group.
Em biological systems, methylation is catalysed by enzymes; such methylations may be involved in the modification of heavy metals, regulation of gene expression, regulation of protein functions, is RNA metabolism. Methylation of heavy metals can also occur outside biological systems. Chemical methylation of tissue samples is also a method to reduce certain artifacts of histological staining.
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