HIV Accelerates Aging by 5 Years



Four epigenetic "clock" measures, spanning from 1.9 to 4.8 years, revealed a significant age acceleration in HIV-infected individuals that was not present in non-infected individuals. (Image: An HIV-infected immunological cell.) Photograph courtesy of the National Institute of Allergy and Infectious Diseases (NIAID)

A UCLA-led study found that alterations at the DNA level can speed up aging by about five years.

Researchers at the University of California, Los Angeles claim that HIV has a "early and substantial" impact on how quickly infected individuals age, increasing biochemical changes in the body linked to normal aging within two to three years of infection.

The findings suggest that a new HIV infection may reduce a person's life expectancy by about five years when compared to someone who is not affected.

Lead author Elizabeth Crabb Breen, a professor emerita at UCLA's Cousins Center for Psychoneuroimmunology and of psychiatry and biobehavioral sciences at the David Geffen School of Medicine, said, "Our work demonstrates that even in the early months and years of living with HIV, the virus has already set into motion an accelerated aging process at the DNA level." This highlights the vital relevance of early HIV diagnosis, the value of preventing HIV infection in the first place, and awareness of aging-related issues.                                                                           
Previous research has shown a connection between HIV and the antiretroviral medications used to treat the virus and an earlier onset of age-related illnesses such heart and renal disease, frailty, and cognitive decline.

The researchers looked at blood samples from 102 guys that were taken two to three years and six months or less before they became HIV. They were contrasted with samples obtained from 102 guys of the same age who were not affected over the same time period. This study is the first to compare infected and non-infected patients in this way, according to the authors. The Multicenter AIDS Cohort Study, a nationwide investigation that started in 1984, included all of the men.

The focus of the study was on how HIV impacts epigenetic DNA methylation, a mechanism by which cells switch on or off genes in response to physiologically normal alterations. The term "epigenetic modifications" refers to those created in response to environmental influences, human actions, or other exogenous causes, such as disease, that modify how genes function without altering the genes themselves.

The group looked at five aging-related epigenetic indicators. Four of them are what are referred to as epigenetic "clocks," and each one calculates biological age acceleration in years in relation to chronological age using a slightly different methodology. The length of telomeres, the protective caps-like ends of chromosomes that get shorter with age when cells divide, until they get so short that division is no longer viable, was measured in the fifth measurement.

In the absence of highly active antiretroviral therapy, HIV-infected individuals demonstrated significant age acceleration in each of the four epigenetic clock measurements, ranging from 1.9 to 4.8 years, as well as telomere shortening over the time frame starting just before infection and ending two to three years after. The non-infected participants did not experience a similar age acceleration within the same time period.

"This study's design leaves no doubt about the significance of HIV in eliciting biochemical signs of early aging," said senior author Beth Jamieson, a professor in the division of hematology and oncology at the Geffen School. "We had access to rare, well-characterized samples." Our long-term objective is to find out if we can use any of these characteristics to forecast if a person is at elevated risk for particular aging-related illness outcomes, exposing new targets for intervention treatments.

The study had several restrictions, according to the researchers. The study only involved men, therefore its findings might not apply to women. Additionally, there were insufficient non-White participants, and the sample size was too small to account for the long-term effects of highly active antiretroviral therapy or to forecast clinical outcomes.

According to the researchers, there is still no agreement on what normal aging is or how to quantify it.

Elizabeth Crabb Breen, Mary E. Sehl, Roger Shih, Peter Langfelder, Ruibin Wang, Steve Horvath, Jay H. Bream, Priya Duggal, Jeremy Martinson, Steven M. Wolinsky, Otoniel Martnez-Maza, Christina M. Ramirez, and Beth D. Jamieson, "Accelerated aging with HIV begins at the time of initial HIV infection," iScience, 30 June 2022. DOI: 10.10

The Multicenter AIDS Cohort Study, or MACS, is a large-scale research effort that examines the natural and treated histories of HIV infection and AIDS using demographic characteristics, habits, disease histories, and sexual histories among men who have sex with males. One of the few cohort studies in the world that has biological samples available both before and after individuals have been shown to have contracted HIV. The MACS/WIHS Combined Cohort Study, or MWCCS, was created in 2019 by combining MACS with the Women's Interagency HIV Study.

The National Institute on Aging, the National Heart, Lung, and Blood Institute, as well as the Susan G. Komen Career Catalyst Award, provided funding for the study.

By UNIVERSITY OF CALIFORNIA - LOS ANGELES HEALTH SCIENCES  

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