HIV, pathology and epigenetic age acceleration in different human tissues

Area of Science:

• Genomics and Epigenetics
• Aging Research
• Human Pathology

Background:

• Epigenetic clocks, based on DNA methylation, are crucial for aging and disease research.
• Fundamental questions remain regarding the correlation of epigenetic age acceleration (EAA) across different tissues and its association with clinical conditions.
• Human Immunodeficiency Virus-1 (HIV) infection is associated with accelerated aging, making it a key focus for studying EAA in various tissues.

Purpose of the Study:

• To investigate the correlation of EAA across 11 human tissue types.
• To determine the relationship between tissue pathology, clinical illness, and EAA in target organs.
• To examine sex-based differences in EAA variability across tissues, particularly in a cohort enriched for HIV-infected individuals.

Main Methods:

• Generated DNA methylation data from 661 samples across 11 tissues using a custom methylation array.
• Included 133 clinically characterized deceased individuals, with 75 infected with HIV.
• Developed a multimorbidity index based on clinical disease history.

Main Results:

• Epigenetic age showed moderate correlations across tissues; blood exhibited the strongest correlations, particularly with spleen and bone marrow, but not liver.
• Liver EAA weakly correlated with EAA in kidney, adipose, lung, and bone marrow.
• Hypertension associated with EAA in multiple tissues; HIV infection linked to positive EAA in kidney and spleen; male sex associated with increased EAA in several tissues; greater multimorbidity correlated with higher EAA across all tissues.

Conclusions:

• Blood EAA alone is insufficient to represent EAA in other tissues.
• Hypertension is associated with widespread EAA, while many pathologies exhibit organ-specific age acceleration.
• EAA is influenced by clinical factors such as HIV infection, multimorbidity, and sex, highlighting tissue-specific responses to disease and aging.