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Background

Substance Use Disorder (SUD) contributes to the early onset of age-related diseases and mortality. Although Accelerated Aging (AA) in people with SUD (pSUD) is a key factor in these outcomes, as indicated by changes in Epigenetic Clocks (EC), existing assessments of AA in pSUD primarily utilize ECs designed for non-brain tissues.

Methods

We used two brain-specific ECs (DNAmClockCortical and PCBrainAge) to examine postmortem brain samples (bulk-BA9 tissue) from 61 pSUD and 19 controls. K-mean cluster analysis was used to identify pSUD with (SUD+ AA, n= 30) and without AA (SUD-AA, n= 31). We compared differentially expressed genes (DEGs) and differentially methylated probes (DMP) between groups, extended by functional enrichment for biological interpretation.

Results

RNA sequencing revealed 66 DEGs (fold-change> 0.5, FDR> 0.2), including genes known for their role in …