HIV accelerates epigenetic aging shortly after first HIV infection

According to a study by UCLA researchers and colleagues, HIV has an “early and substantial” impact on aging in infected people, accelerating biological changes in the body associated with normal aging within just two to three years of infection.

The findings suggest that a new HIV infection can quickly shorten a person’s lifespan by nearly five years relative to an uninfected person.

Our work shows that even in the early months and years of living with HIV, the virus has already initiated an accelerated aging process at the DNA level. This highlights the critical importance of early HIV diagnosis and awareness of aging-related issues, as well as the value of preventing HIV infection in the first place.”


Elizabeth Crabb Breen, lead author, professor emeritus at UCLA’s Cousins ​​Center for Psychoneuroimmunology and of psychiatry and biobehavioural sciences at the David Geffen School of Medicine at UCLA

The study is published today in the peer-reviewed journal iScience

Previous research has suggested that HIV and antiretroviral therapies used to control infection are associated with an earlier onset of age-related conditions typically associated with aging, such as heart and kidney disease, frailty and cognitive problems.

The research team analyzed stored blood samples from 102 men collected six months or less before becoming infected with HIV and again two to three years after infection. They compared these to matched samples from 102 uninfected men of the same age taken over the same period. The authors say this study is the first to match infected and uninfected people in this way. All men participated in the Multicenter AIDS Cohort Study, an ongoing nationwide study that began in 1984.

The researchers focused on how HIV affects epigenetic DNA methylation, a process cells use to turn genes on or off in the course of normal physiological changes. epigenetic changes are those made in response to the influence of the environment, people’s behavior or other external factors -; like illness -; that affect how genes behave without changing the genes themselves.

The team examined five measures of epigenetic aging. Four of them are so-called epigenetic “clocks,” each of which uses a slightly different approach to estimate biological age acceleration in years, relative to chronological age. The fifth measure assessed the length of telomeres, the protective cap-like ends of chromosomes that shorten with age as cells divide, until they become so short that division is no longer possible.

HIV-infected individuals showed significant age acceleration in each of the four epigenetic clock measures -; ranging from 1.9 to 4.8 years -; as well as telomere shortening during the period beginning just before infection and ending two to three years afterwards, in the absence of highly active antiretroviral treatment. Similar age acceleration was not seen in the uninfected participants during the same time interval.

“Our access to rare, well-characterized samples allowed us to design this study in a way that leaves little doubt about HIV’s role in eliciting biological features of early aging,” said senior author Beth Jamieson, a professor in the hematology department. and oncology at the Geffen School. “Our long-term goal is to determine whether we can use any of these signatures to predict whether a person is at increased risk for specific aging-related disease outcomes, uncovering new targets for therapeutic interventions.”

The researchers noted some limitations to the study. It only included men, so the results may not apply to women. In addition, the number of non-white participants was small and the sample size was insufficient to account for subsequent effects of highly active antiretroviral treatment or to predict clinical outcomes.

There is still no consensus on what normal aging entails or how to define it, the researchers wrote.

The Multicenter AIDS Cohort Study, or MACS, is a large-scale research project that uses demographic factors, habits, medical history, and sexual history in men who have sex with men to examine the natural and treated history of HIV infection and AIDS. It is one of the few cohort studies in the world where biological samples are available both before and after documented HIV infection in the same individuals. In 2019, MACS was combined with the Women’s Interagency HIV Study to form the MACS/WIHS Combined Cohort Study, or MWCCS.

Source:

Reference magazine:

Breen, EC, et al. (2022) Accelerated aging with HIV starts at the time of the first HIV infection. iScience. doi.org/10.1016/j.isci.2022.104488

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