Recent epigenetic findings published in Molecular Cell showed that HIV infection prematurely ages people by an average of 5 years, even while being treated with ART.
“Antiretroviral treatment has greatly reduced the morbidity and mortality due to HIV infection. However, there are many indications that people living with HIV are at increased risk for non-AIDS, age-related diseases thought to indicate accelerated aging,” Howard S. Fox, MD, PhD, professor in the department of pharmacology and experimental neuroscience at the University of Nebraska Medical Center, told Infectious Disease News. “Here we have used epigenetic markers to provide a biological clock for aging and HIV. And indeed, we find in those with HIV, there is an increase in the calculated biologic age relative to chronological age.”
Howard S. Fox
According to Fox and colleagues, several studies have suggested links between chronic HIV infection and early onset of cancer, liver failure, kidney failure, neurodegeneration and cardiovascular disease. This led to the hypothesis that patients with HIV experience accelerated aging, although the exact number of years aged remained unknown, in part due to the lack of an objective biological clock. With the development of epigenetic models, however, researchers can predict a person’s biological age. These models use DNA methylation patterns across a large number of cytosine-phosphate-guanine (CpG) sites correlated with the aging process.
Fox and colleagues conducted a global analysis of the whole-blood DNA methylomes of 137 patients with HIV undergoing sustained ART along with 44 matched participants without HIV. They analyzed these methylomes using validated epigenetic models of aging.
The researchers determined that both chronic and recent HIV infection led to an average biological aging advancement of 4.9 years and increased the expected mortality risk by 19%. Further, sustained infection led to global regulation of the methylome across more than 80,000 CpG sites as well as specific hypomethylation of the region encoding the human leukocyte antigen (HLA) locus. This decline in hypomethylation of the HLA is predictive of a lower CD4/CD8 cell ratio, the investigators wrote.
These results, in combination with evidence suggesting a link between molecular age acceleration and increased mortality risk, support the idea that chronic HIV infection is accompanied by a tangible gerontological phenotype, Fox and colleagues reported.
“This is worrisome for potential increased risk of aging-related diseases as well as overall risk of mortality, and emphasizes the need for promoting healthy aging in those with HIV through minimizing other risk factors,” Fox said. “These studies provide a biomarker for age advancement in HIV infection, useful now for research studies but may be applied in the future for specific disease markers.” – by Will Offit
Disclosure: The researchers report no relevant financial disclosures.