Aging Diseases Come to HIV-Pozzers a Decade Early

People undergoing treatment for HIV-1 are at increased risk for earlier onset of age-related illnesses such as some cancers, renal and kidney disease, frailty, osteoporosis and neurocognitive disease. But the question arises: is the cause of this the virus that causes AIDS or the treatment?

To answer this question, researchers from the UCLA AIDS Institute and Center for AIDS Research, and the Multi-Center AIDS Cohort Study (MACS) investigated whether the virus induces age-associated epigenetic changes -- that is, changes to the DNA that in turn lead to changes in expression of gene levels without changing the inherited genetic code. These changes affect biological processes and can be brought on by environmental factors or by the aging process itself.

In a study published March 25 in the peer-reviewed online journal PLOS ONE, the researchers suggest that HIV itself accelerates these aging related changes by more than 14 years.

"While we were surprised by the number of epigenetic changes that were significantly associated with both aging and HIV-infection, we were most surprised that the data suggests HIV-infection can accelerate aging-related epigenetic changes by 13.7 to 14.7 years," said Beth Jamieson, professor of medicine in the division of hematology/oncology at the David Geffen School of Medicine at UCLA, director of the UCLA Flow Cytometry Core and one of the study's senior authors. "This number is in line with both anecdotal and published data suggesting that treated HIV-infected adults can develop the diseases of aging mentioned above, approximately a decade earlier than their uninfected peers."

The researchers examined samples of white blood cells stored by the UCLA site of the MACS, which has been collecting biological samples as well as clinical, behavioral, and socio-economic data on HIV-infected men and men at risk for infection since 1983. They selected white blood cell samples from both young (20 to 35 years old) and older (36 to 56 years old) adults who at the time had not started antiretroviral therapy (ART). They divided each age group into 12 HIV-infected and 12 age-matched HIV-uninfected samples for a total of 96 samples. The researchers then extracted the DNA from the samples and analyzed the DNA for epigenetic patterns.

They compared epigenetic patterns that are strongly associated with aging to changes that occur during HIV-infection and found significant overlap in the two patterns, Jamieson said. They used those overlapping patterns to estimate the biological age of HIV-infected, untreated adults, and found that at the epigenetic level, the adults appeared to be approximately 14 years older than their chronologic age.

Jamieson noted that the cells they used were taken from men before they began taking ART. Although the findings demonstrate that HIV-infection can accelerate aging related epigenetics, the researchers cannot determine at this point if ART restores those patterns to be more age-appropriate or whether the drugs themselves cause additional changes.

Taken together, however, "these data suggest that HIV-1 infection does accelerate some aspects of aging and that general aging, and HIV-1 related aging, work through at least some common mechanisms," the authors write. "These results are an important first step for finding potential therapeutic approaches to mitigate the effects of both HIV and aging.

Study co-authors are Tammy M. Rickabaugh, Ruth M. Baxter, Mary Sehl, Janet S. Sinsheimer, Patricia Hultin, Lance Hultin, Austin Quach, Otoniel Martinez-Maza, Steve Horvath, and Eric Vilain, all of UCLA.

This study was supported by NIA Grant 1RO1-AG-030327 awarded to B.D. Jamieson, P.I., NIAID AI-035040 R. Detels and O. Martinez-Maza joint P.I.s, B.D. Jamieson Co-Investigator, and by a UCLA AIDS Institute/CFAR Seed Grant from the National Institutes of Health award AI-028697 given to Dr. Eric Vilain, P.I. Ruth Baxter was supported by a NIH T032 training grant #5T32GM008243-25. Janet Sinsheimer is partially funded by NSF grant DMS-1264153.