Global DNA methylation and telomere length as markers of accelerated ageing in non-alcoholic fatty liver disease patients with HIV infection

Abstract Metabolic-dysfunction-associated fatty liver disease (MAFLD) is a comorbidity that generally increases in people living with HIV (PLWH). This condition is usually accompanied by persistent inflammation and premature immune system ageing. In this prospective cohort study, we describe a straightforward methodology for quantifying the effect of HIV on aging factors compared with other relevant conditions, such as MAFLD, by quantifying DNA methylation and telomere length. Fifty-seven samples in total, thirty-eight from HIV-infected and nineteen from HIV-uninfected participants with or without MAFLD, were obtained and subjected to DNA extraction from peripheral blood mononuclear cells (PBMCs). DNA methylation and telomere length quantification were performed using an adapted enzyme-linked immunosorbent assay (ELISA) and qPCR, respectively. The quantification results were analysed and corrected by clinically relevant variables in this context, such as age, sex, and metabolic syndrome. The results showed an increased association with these age-acceleration markers in individuals with HIV, who were also diagnosed with MAFLD. This highlights the importance of HIV infection and MAFLD conditions in the biological ageing process in PLWH, and the fact that these markers of ageing can be measured through DNA methylation and telomere length quantification. Thus, we propose including these quantifications in studies of comorbidities to better understand them and potentially prevent their effects in this population.