Acceleration of epigenetic clock
These studies establish a scenario using methylation patterns to investigate whether people with HIV advancing the organic age more quickly than uninfected said Ideker that for the new study worked with Howard S. Fox, MD, PhD, professor and vice executive-chair of pharmacology and experimental neuroscience at the Medical Center of the University of Nebraska at Omaha.
His research team took blood samples from a total of 137 non-Hispanic white men aged 25 68 the years that have been infected with HIV and taking antiretroviral therapy. In addition, they took blood samples from 44 non-Hispanic healthy individuals, white men and not infected with HIV. The research team isolated DNA from these samples and analyzed the whole genome methylation patterns using molecular techniques.
The results showed 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% increase in mortality risk. In contrast, biological and chronological ages of their healthy counterparts were closely aligned. All except 15 of HIV-infected men had some degree of age, Ideker said.
"The beauty of this marker is that it is very fast, quantitative and conclusive," Ideker said.
Data on methylation were what researchers and clinicians needed to validate the anecdotal observations that people with HIV age faster, noted Fox.
"The epigenetic clock methylone provides the increased mortality or morbidity is accelerated and [our study] really showed that this watch was enhanced in patients with HIV," Fox said.
In addition to accelerated aging in individuals with HIV and Fox Ideker 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," Ideker said, noting that perhaps the elderly rate is constant over time or, alternatively, the tests do not have the power to detect subtle differences in the acceleration of age among those which they have recently infected and those who had been infected for years.
Viruses or drugs?
What is not clear is whether this accelerated aging is due to the effect of the virus itself or long-term antiretroviral therapy. The resulting chronic inflammation of viral infection may be leading the early onset of age-related morbidities in HIV-positive patients, noted Larry Corey, MD, University of Washington Medical School professor and past president of the Cancer Research Center Fred Hutchinson Seattle. Corey headed AIDS Clinical Trial Group em 1987.
"We know clinically that HIV causes a continuous inflammatory response," said Corey.
While it is possible that antiretroviral drugs can play a role in accelerated aging, Corey said it is unlikely because this accelerated aging seems to occur among HIV patients, no matter what combination of antiretroviral drugs that they are using. Instead, he suspects that the reactivation of latent HIV reservoirs can contribute to the process.
In any case, it is a moot point because HIV is fatal if the patient does not take the antiretroviral medication, Fox said.
Another question that remains is that accelerated aging rate occurs among HIV-infected women and people of different racial groups, noted Carl Dieffenbach, PhD, AIDS division director of the National Institute of Allergy and Infectious Diseases, who was not involved with study.
"The aging of women is a bit more complicated with the effect of estrogen," said Dieffenbach.
The study is solid and well made and points to research on HIV to 'very interesting directions, "said Dieffenbach.
A discovery with pontenciais clinical implications, Dieffenbach noted, is that the human leukocyte antigen (HLA) genes that regulate the acquired immune response, were hypomethylated in HIV-infected men.
"The direction that points us is that other diseases are associated with [HLA] hypomethylation?" Dieffenbach said.
The researchers also found that hypomethylation is associated with HIV status and may be related to the control of infection and subsequent inflammation. inflammation
caused by HIV infection, in turn, may be associated with early onset of unrelated diseases with AIDS, such as cardiovascular disease and cognitive impairment in HIV positive patients, Fox said. He noted that this finding supports their overall conclusion that the advanced biological aging predicts increased morbidity and mortality.
Another interesting question that the study raises, Dieffenbach said, is whether the accelerated aging can be alleviated 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 fact that drugs have become better and better, the carriers of HIV infection show a 5 deficit to 7 years in expectation and quality of life."
Slowing the clock
Along these lines, the results of this study may encourage continued research lifestyle and adjunctive pharmacological interventions that could potentially delay the onset of diseases related to age in HIV-positive individuals, noted Ideker. For example, a study currently underway is examining whether statins can reduce the risk of cardiovascular disease among HIV positive patients adults aged 40 75 the years that are taking antiretroviral therapy with no 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 drawn attention to the possible link between inflammation and diseases related to age 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 suggests that Foxsugere Ideker and HLA gene may be a potential drug target to prevent early onset of diseases related to age associated with chronic inflammation, said Dieffenbach.
"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 pair 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 to denote chemical sciences connection or replacement ofmethyl groupon varioussubstrates. The term is commonly used inchemistry, biochemistry, Sciencealoneand biological sciences.
In biochemistry, methylation refers more specifically to the replacement of one atom ofhydrogenthe methyl group.
Inbiological systems, Methylation iscatalysed forenzymes; such methylations may be involved in the modificationheavy metals, Regulationgene expression, Regulationprotein functions, AndRNA metabolism. Methylation of heavy metals can also occur outside of biological systems. The chemical methylation of tissue samples is also a method for reducing certainartifacts of histological staining.